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Gene regulatory networks

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https://www.readbyqxmd.com/read/28212969/lessons-learned-when-introducing-pharmacogenomic-panel-testing-into-clinical-practice
#1
Marc B Rosenman, Brian Decker, Kenneth D Levy, Ann M Holmes, Victoria M Pratt, Michael T Eadon
OBJECTIVES: Implementing new programs to support precision medicine in clinical settings is a complex endeavor. We describe challenges and potential solutions based on the Indiana GENomics Implementation: an Opportunity for the Underserved (INGenious) program at Eskenazi Health-one of six sites supported by the Implementing GeNomics In pracTicE network grant of the National Institutes of Health/National Human Genome Research Institute. INGenious is an implementation of a panel of genomic tests...
January 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/28212624/understanding-the-response-to-endurance-exercise-using-a-systems-biology-approach-combining-blood-metabolomics-transcriptomics-and-mirnomics-in-horses
#2
Núria Mach, Yuliaxis Ramayo-Caldas, Allison Clark, Marco Moroldo, Céline Robert, Eric Barrey, Jesús Maria López, Laurence Le Moyec
BACKGROUND: Endurance exercise in horses requires adaptive processes involving physiological, biochemical, and cognitive-behavioral responses in an attempt to regain homeostasis. We hypothesized that the identification of the relationships between blood metabolome, transcriptome, and miRNome during endurance exercise in horses could provide significant insights into the molecular response to endurance exercise. For this reason, the serum metabolome and whole-blood transcriptome and miRNome data were obtained from ten horses before and after a 160 km endurance competition...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28209995/rna-seq-based-transcriptomic-and-metabolomic-analysis-reveal-stress-responses-and-programmed-cell-death-induced-by-acetic-acid-in-saccharomyces-cerevisiae
#3
Yachen Dong, Jingjin Hu, Linlin Fan, Qihe Chen
As a typical harmful inhibitor in cellulosic hydrolyzates, acetic acid not only hinders bioethanol production, but also induces cell death in Saccharomyces cerevisiae. Herein, we conducted both transcriptomic and metabolomic analyses to investigate the global responses under acetic acid stress at different stages. There were 295 up-regulated and 427 down-regulated genes identified at more than two time points during acetic acid treatment (150 mM, pH 3.0). These differentially expressed genes (DEGs) were mainly involved in intracellular homeostasis, central metabolic pathway, transcription regulation, protein folding and stabilization, ubiquitin-dependent protein catabolic process, vesicle-mediated transport, protein synthesis, MAPK signaling pathways, cell cycle, programmed cell death, etc...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209158/gene-regulatory-network-underlying-the-immortalization-of-epithelial-cells
#4
Luis Fernando Méndez-López, Jose Davila-Velderrain, Elisa Domínguez-Hüttinger, Christian Enríquez-Olguín, Juan Carlos Martínez-García, Elena R Alvarez-Buylla
BACKGROUND: Tumorigenic transformation of human epithelial cells in vitro has been described experimentally as the potential result of spontaneous immortalization. This process is characterized by a series of cell-state transitions, in which normal epithelial cells acquire first a senescent state which is later surpassed to attain a mesenchymal stem-like phenotype with a potentially tumorigenic behavior. In this paper we aim to provide a system-level mechanistic explanation to the emergence of these cell types, and to the time-ordered transition patterns that are common to neoplasias of epithelial origin...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28209126/a-meta-analysis-reveals-complex-regulatory-properties-at-taf14-repressed-genes
#5
Josipa Nemet, Nikolina Vidan, Mary Sopta
BACKGROUND: Regulation of gene transcription in response to stress is central to a cell's ability to cope with environmental challenges. Taf14 is a YEATS domain protein in S.cerevisiae that physically associates with several transcriptionally relevant multisubunit complexes including the general transcription factors TFIID and TFIIF and the chromatin-modifying complexes SWI/SNF, INO80, RSC and NuA3. TAF14 deletion strains are sensitive to a variety of stresses suggesting that it plays a role in the transcriptional stress response...
February 16, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28208333/stochastic-liouville-equation-for-particles-driven-by-dichotomous-environmental-noise
#6
Paul C Bressloff
We analyze the stochastic dynamics of a large population of noninteracting particles driven by a global environmental input in the form of a dichotomous Markov noise process (DMNP). The population density of particle states evolves according to a stochastic Liouville equation with respect to different realizations of the DMNP. We then exploit the connection with previous work on diffusion in randomly switching environments, in order to derive moment equations for the distribution of solutions to the stochastic Liouville equation...
January 2017: Physical Review. E
https://www.readbyqxmd.com/read/28207192/temporal-spatial-establishment-of-initial-niche-for-the-primary-spermatogonial-stem-cell-formation-is-determined-by-an-arid4b-regulatory-network
#7
Ray-Chang Wu, Yang Zeng, Yu-Fang Chen, Rainer B Lanz, Mei-Yi Wu
During neonatal testis development, centrally located gonocytes migrate to basement membrane of the seminiferous cords, where physical contact with a niche established by Sertoli cells is essential for transition of gonocytes into spermatogonial stem cells (SSCs). To provide structural support and signaling stimuli for the gonocyte-to-SSC transition that occurs at a specific location during a finite phase, temporal-spatial establishment of the niche is critical. To date, the factors that guide Sertoli cells to establish the initial stem cell niche remain largely unknown...
February 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28207000/spatial-transcriptomic-analysis-of-cryosectioned-tissue-samples-with-geo-seq
#8
Jun Chen, Shengbao Suo, Patrick Pl Tam, Jing-Dong J Han, Guangdun Peng, Naihe Jing
Conventional gene expression studies analyze multiple cells simultaneously or single cells, for which the exact in vivo or in situ position is unknown. Although cellular heterogeneity can be discerned when analyzing single cells, any spatially defined attributes that underpin the heterogeneous nature of the cells cannot be identified. Here, we describe how to use Geo-seq, a method that combines laser capture microdissection (LCM) and single-cell RNA-seq technology. The combination of these two methods enables the elucidation of cellular heterogeneity and spatial variance simultaneously...
March 2017: Nature Protocols
https://www.readbyqxmd.com/read/28205554/the-oncoppi-network-of-cancer-focused-protein-protein-interactions-to-inform-biological-insights-and-therapeutic-strategies
#9
Zenggang Li, Andrei A Ivanov, Rina Su, Valentina Gonzalez-Pecchi, Qi Qi, Songlin Liu, Philip Webber, Elizabeth McMillan, Lauren Rusnak, Cau Pham, Xiaoqian Chen, Xiulei Mo, Brian Revennaugh, Wei Zhou, Adam Marcus, Sahar Harati, Xiang Chen, Margaret A Johns, Michael A White, Carlos Moreno, Lee A D Cooper, Yuhong Du, Fadlo R Khuri, Haian Fu
As genomics advances reveal the cancer gene landscape, a daunting task is to understand how these genes contribute to dysregulated oncogenic pathways. Integration of cancer genes into networks offers opportunities to reveal protein-protein interactions (PPIs) with functional and therapeutic significance. Here, we report the generation of a cancer-focused PPI network, termed OncoPPi, and identification of >260 cancer-associated PPIs not in other large-scale interactomes. PPI hubs reveal new regulatory mechanisms for cancer genes like MYC, STK11, RASSF1 and CDK4...
February 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28205287/upstream-regulation-for-initiation-of-restricted-shh-expression-in-the-chick-limb-bud
#10
Haruka Matsubara, Daisuke Saito, Gembu Abe, Hitoshi Yokoyama, Takayuki Suzuki, Koji Tamura
Background The organizing center, which serves as a morphogen source, has crucial functions in morphogenesis in animal development. The center is necessarily located in a certain restricted area in the morphogenetic field, and there are several ways in which an organizing center can be restricted. The organizing center for limb morphogenesis, the ZPA (zone of polarizing activity), specifically expresses the Shh gene and is restricted to the posterior region of the developing limb bud. Results The prepattern along the limb antero-posterior axis, provided by anterior Gli3 expression and posterior Hand2 expression, seems insufficient for the initiation of Shh expression restricted to a narrow, small spot in the posterior limb field...
February 16, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28203683/identification-of-unique-venous-thromboembolism-susceptibility-variants-in-african-americans
#11
John A Heit, Sebastian M Armasu, Bryan M McCauley, Iftikhar J Kullo, Hugues Sicotte, Jyotishman Pathak, Christopher G Chute, Omri Gottesman, Erwin P Bottinger, Joshua C Denny, Dan M Roden, Rongling Li, Marylyn D Ritchie, Mariza de Andrade
To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype...
February 16, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28203648/gene-regulatory-effects-of-disease-associated-variation-in-the-nrf2-network
#12
Sarah E Lacher, Matthew Slattery
Reactive oxygen species (ROS), which are both a natural byproduct of oxidative metabolism and an undesirable byproduct of many environmental stressors, can damage all classes of cellular macromolecules and promote diseases from cancer to neurodegeneration. The actions of ROS are mitigated by the transcription factor NRF2, which regulates expression of antioxidant genes via its interaction with cis-regulatory antioxidant response elements (AREs). However, despite the seemingly straightforward relationship between the opposing forces of ROS and NRF2, regulatory precision in the NRF2 network is essential...
December 2016: Curr Opin Toxicol
https://www.readbyqxmd.com/read/28203225/regulation-of-sterol-biosynthesis-in-the-human-fungal-pathogen-aspergillus-fumigatus-opportunities-for-therapeutic-development
#13
REVIEW
Sourabh Dhingra, Robert A Cramer
Sterols are a major component of eukaryotic cell membranes. For human fungal infections caused by the filamentous fungus Aspergillus fumigatus, antifungal drugs that target sterol biosynthesis and/or function remain the standard of care. Yet, an understanding of A. fumigatus sterol biosynthesis regulatory mechanisms remains an under developed therapeutic target. The critical role of sterol biosynthesis regulation and its interactions with clinically relevant azole drugs is highlighted by the basic helix loop helix (bHLH) class of transcription factors known as Sterol Regulatory Element Binding Proteins (SREBPs)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28202516/modeling-the-genetic-regulation-of-cancer-metabolism-interplay-between-glycolysis-and-oxidative-phosphorylation
#14
Linglin Yu, Mingyang Lu, Dongya Jia, Jianpeng Ma, Eshel Ben-Jacob, Herbert Levine, Benny A Kaipparettu, Jose' N Onuchic
Abnormal metabolism is a hallmark of cancer, yet its regulation remains poorly understood. Cancer cells were considered to utilize primarily glycolysis for ATP production, referred to as the Warburg effect. However, recent evidence suggests that oxidative phosphorylation (OXPHOS) plays a crucial role during cancer progression. Here we utilized a systems biology approach to decipher the regulatory principle of glycolysis and OXPHOS. Integrating information from literature, we constructed a regulatory network of genes and metabolites from which we extracted a core circuit containing HIF-1, AMPK, and ROS...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28201990/a-vast-genomic-deletion-in-the-c56bl-6-genome-affects-different-genes-within-the-ifi200-cluster-on-chromosome-1-and-mediates-obesity-and-insulin-resistance
#15
Heike Vogel, Markus Jähnert, Mandy Stadion, Daniela Matzke, Stephan Scherneck, Annette Schürmann
BACKGROUND: Obesity, the excessive accumulation of body fat, is a highly heritable and genetically heterogeneous disorder. The complex, polygenic basis for the disease consisting of a network of different gene variants is still not completely known. RESULTS: In the current study we generated a BAC library of the obese-prone NZO strain to clarify the genomic alteration within the gene cluster Ifi200 on chr.1 including Ifi202b, an obesity gene that is in contrast to NZO not expressed in the lean B6 mouse...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28198367/usp9x-regulates-ets-1-ubiquitination-and-stability-to-control-nras-expression-and-tumorigenicity-in-melanoma
#16
Harish Potu, Luke F Peterson, Malathi Kandarpa, Anupama Pal, Hanshi Sun, Alison Durham, Paul W Harms, Peter C Hollenhorst, Ugur Eskiocak, Moshe Talpaz, Nicholas J Donato
ETS transcription factors are commonly deregulated in cancer by chromosomal translocation, overexpression or post-translational modification to induce gene expression programs essential in tumorigenicity. Targeted destruction of these proteins may have therapeutic impact. Here we report that Ets-1 destruction is regulated by the deubiquitinating enzyme, Usp9x, and has major impact on the tumorigenic program of metastatic melanoma. Ets-1 deubiquitination blocks its proteasomal destruction and enhances tumorigenicity, which could be reversed by Usp9x knockdown or inhibition...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28197719/regulatory-crosstalk-between-micrornas-and-hormone-signalling-cascades-controls-the-variation-on-seed-dormancy-phenotype-at-arabidopsis-thaliana-seed-set
#17
Yang Liu, Yousry A El-Kassaby
We employed an Illumina sequencing approach to identify candidate microRNA cohorts that may greatly contribute to seed dormancy modulation and to construct a microRNA-gene regulatory network in hormone signalling cascades. MicroRNAs (miRNAs) are important signalling molecules and regulate many developmental programs of plants. Some miRNAs have been integrated into gene regulatory networks (GRNs) and coordinate developmental plasticity, but few study systematically investigated how phenotypical variations are regulated through differential expression of miRNA tags in GRNs during seed set...
February 14, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28197378/identification-of-inhibitors-of-myeloid-derived-suppressor-cells-activity-through-phenotypic-chemical-screening
#18
Matthias Schröder, Simone Loos, Svenja Kerstin Naumann, Christopher Bachran, Marit Krötschel, Viktor Umansky, Laura Helming, Lee Kim Swee
Tumors are infiltrated by cells of the immune system that interact through complex regulatory networks. Although tumor-specific CD8(+) T cells can be found in peripheral blood and tumor samples from cancer patients, their function is inhibited by immunosuppressive cells such as regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells (MDSC). Recent clinical successes have demonstrated that alleviating immunosuppression and T cell exhaustion translates into long-term clinical benefits...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196122/detrimental-elavl-1-hur-dependent-gsk3%C3%AE-mrna-stabilization-impairs-resolution-in-acute-respiratory-distress-syndrome
#19
Olivia Hoffman, Nana Burns, István Vadász, Holger K Eltzschig, Michael G Edwards, Christine U Vohwinkel
A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3β during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3β could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3β messenger RNA utilizing two lung cancer cell line array datasets...
2017: PloS One
https://www.readbyqxmd.com/read/28195723/drug-discovery-targeting-bromodomain-containing-protein-4-brd4
#20
Zhiqing Liu, Pingyuan Wang, Haiying Chen, Eric A Wold, Bing Tian, Allan R Brasier, Jia Zhou
BRD4, the most extensively studied member of BET family, is an epigenetic regulator that localizes to DNA via binding acetylated histones and controls the expression of therapeutically important gene regulatory networks through recruiting transcription factors to form mediator complexes, phosphorylating RNA polymerase II and by its intrinsic histone acetyltransferase activity. Disrupting the protein-protein interactions between BRD4 and acetyl-lysine has been shown to effectively block cell proliferation in cancer, cytokine production in acute inflammation, etc...
February 14, 2017: Journal of Medicinal Chemistry
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