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Gene regulatory network

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https://www.readbyqxmd.com/read/29352257/robust-phenotype-prediction-from-gene-expression-data-using-differential-shrinkage-of-co-regulated-genes
#1
Kourosh Zarringhalam, David Degras, Christoph Brockel, Daniel Ziemek
Discovery of robust diagnostic or prognostic biomarkers is a key to optimizing therapeutic benefit for select patient cohorts - an idea commonly referred to as precision medicine. Most discovery studies to derive such markers from high-dimensional transcriptomics datasets are weakly powered with sample sizes in the tens of patients. Therefore, highly regularized statistical approaches are essential to making generalizable predictions. At the same time, prior knowledge-driven approaches have been successfully applied to the manual interpretation of high-dimensional transcriptomics datasets...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29351440/jq1-is-a-potential-therapeutic-option-for-copd-patients-with-agrin-overexpression
#2
Zhen Xiao, Jing Shu, Feng Zhou, Yong Han
Chronic Obstructive Pulmonary Disease (COPD) is one of the leading cause of morbidity and death worldwide. It is characterized by chronic pulmonary inflammation and obstructed airflow from the lungs. To date, there is no effective treatments for COPD. The activation of Agrin (AGRN) - YAP pathway can promote heart regeneration. Since Agrin can only induce mild cardiomyocyte (CM) proliferation compare to ERBB2 pathway activation, it might exert pleiotropic effects, such as mitigation of innate inflammation, immune response and fibrosis...
December 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351292/allocation-of-distinct-organ-fates-from-a-precursor-field-requires-a-shift-in-expression-and-function-of-gene-regulatory-networks
#3
Sneha Palliyil, Jinjin Zhu, Luke R Baker, Sarah D Neuman, Arash Bashirullah, Justin P Kumar
A common occurrence in metazoan development is the rise of multiple tissues/organs from a single uniform precursor field. One example is the anterior forebrain of vertebrates, which produces the eyes, hypothalamus, diencephalon, and telencephalon. Another instance is the Drosophila wing disc, which generates the adult wing blade, the hinge, and the thorax. Gene regulatory networks (GRNs) that are comprised of signaling pathways and batteries of transcription factors parcel the undifferentiated field into discrete territories...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29349904/lysosome-remodelling-and-adaptation-during-phagocyte-activation
#4
REVIEW
Victoria E B Hipolito, Erika Ospina-Escobar, Roberto J Botelho
Lysosomes are acidic and hydrolytic organelles responsible for receiving and digesting cargo acquired during endocytosis, phagocytosis, and autophagy. For macrophages and dendritic cells, the lysosome is kingpin, playing a direct role in microbe killing and antigen processing for presentation. Strikingly, the historic view that lysosomes are homogeneous and static organelles is being replaced with a more elegant paradigm, in which lysosomes are heterogeneous, dynamic and respond to cellular needs. For example, lysosomes are signaling platforms that integrate stress detection and molecular decision hubs like mTORC1 and AMPK to modulate cellular activity...
January 19, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29348878/identification-of-cancer-prognosis-associated-functional-modules-using-differential-co-expression-networks
#5
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348628/fezf1-as1-mir-107-znf312b-axis-facilitates-progression-and-warburg-effect-in-pancreatic-ductal-adenocarcinoma
#6
Huilin Ye, Quanbo Zhou, Shangyou Zheng, Guolin Li, Qing Lin, Liangtao Ye, Yingxue Wang, Lusheng Wei, Xiaohui Zhao, Wenzhu Li, Zhiqiang Fu, Yimin Liu, Zhihua Li, Rufu Chen
Long non-coding RNAs (lncRNAs) play a pivotal role in pathological processes. However, little information has been published regarding the underlying functions and mechanisms of lncRNAs in pancreatic ductal adenocarcinoma (PDAC). A novel lncRNA FEZF1-AS1 and its sense-cognate gene ZNF312B were found to be highly expressed in human PDAC tissues and cell lines, which is associated with disease progression and predicts clinical outcome in PDAC patients. Of note, bioinformatics analysis, luciferase assays and RNA immunoprecipitation assays indicated that FEZF1-AS1 may act as an endogenous sponge by competing for miR-107, thereby modulating the derepression of ZNF312B...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348497/rna-binding-proteins-control-gene-expression-and-cell-fate-in-the-immune-system
#7
REVIEW
Martin Turner, Manuel D Díaz-Muñoz
RNA-binding proteins (RBPs) are essential for the development and function of the immune system. They interact dynamically with RNA to control its biogenesis and turnover by transcription-dependent and transcription-independent mechanisms. In this Review, we discuss the molecular mechanisms by which RBPs allow gene expression changes to occur at different speeds and to varying degrees, and which RBPs regulate the diversity of the transcriptome and proteome. These proteins are nodes for integration of transcriptional and signaling networks and are intimately linked to intermediary metabolism...
January 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29348434/identification-of-genetic-elements-in-metabolism-by-high-throughput-mouse-phenotyping
#8
Jan Rozman, Birgit Rathkolb, Manuela A Oestereicher, Christine Schütt, Aakash Chavan Ravindranath, Stefanie Leuchtenberger, Sapna Sharma, Martin Kistler, Monja Willershäuser, Robert Brommage, Terrence F Meehan, Jeremy Mason, Hamed Haselimashhadi, Tertius Hough, Ann-Marie Mallon, Sara Wells, Luis Santos, Christopher J Lelliott, Jacqueline K White, Tania Sorg, Marie-France Champy, Lynette R Bower, Corey L Reynolds, Ann M Flenniken, Stephen A Murray, Lauryl M J Nutter, Karen L Svenson, David West, Glauco P Tocchini-Valentini, Arthur L Beaudet, Fatima Bosch, Robert B Braun, Michael S Dobbie, Xiang Gao, Yann Herault, Ala Moshiri, Bret A Moore, K C Kent Lloyd, Colin McKerlie, Hiroshi Masuya, Nobuhiko Tanaka, Paul Flicek, Helen E Parkinson, Radislav Sedlacek, Je Kyung Seong, Chi-Kuang Leo Wang, Mark Moore, Steve D Brown, Matthias H Tschöp, Wolfgang Wurst, Martin Klingenspor, Eckhard Wolf, Johannes Beckers, Fausto Machicao, Andreas Peter, Harald Staiger, Hans-Ulrich Häring, Harald Grallert, Monica Campillos, Holger Maier, Helmut Fuchs, Valerie Gailus-Durner, Thomas Werner, Martin Hrabe de Angelis
Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348408/nipbl-haploinsufficiency-reveals-a-constellation-of-transcriptome-disruptions-in-the-pluripotent-and-cardiac-states
#9
Jason A Mills, Pamela S Herrera, Maninder Kaur, Lanfranco Leo, Deborah McEldrew, Jesus A Tintos-Hernandez, Ramakrishnan Rajagopalan, Alyssa Gagne, Zhe Zhang, Xilma R Ortiz-Gonzalez, Ian D Krantz
Cornelia de Lange syndrome (CdLS) is a complex disorder with multiple structural and developmental defects caused by mutations in structural and regulatory proteins involved in the cohesin complex. NIPBL, a cohesin regulatory protein, has been identified as a critical protein responsible for the orchestration of transcriptomic regulatory networks necessary for embryonic development. Mutations in NIPBL are responsible for the majority of cases of CdLS. Through RNA-sequencing of human induced pluripotent stem cells and in vitro-derived cardiomyocytes, we identified hundreds of mRNAs, pseudogenes, and non-coding RNAs with altered expression in NIPBL+/- patient-derived cells...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29347911/micrornas-associated-with-early-neural-crest-development-in-xenopus-laevis
#10
Nicole J Ward, Darrell Green, Janet Higgins, Tamas Dalmay, Andrea Münsterberg, Simon Moxon, Grant N Wheeler
BACKGROUND: The neural crest (NC) is a class of transitory stem cell-like cells unique to vertebrate embryos. NC cells arise within the dorsal neural tube where they undergo an epithelial to mesenchymal transition in order to migrate and differentiate throughout the developing embryo. The derivative cell types give rise to multiple tissues, including the craniofacial skeleton, peripheral nervous system and skin pigment cells. Several well-studied gene regulatory networks underpin NC development, which when disrupted can lead to various neurocristopathies such as craniofrontonasal dysplasia, DiGeorge syndrome and some forms of cancer...
January 18, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29346554/functional-roles-of-sex-biased-growth-hormone-regulated-micrornas-mir-1948-and-mir-802-in-young-adult-mouse-liver
#11
Pengying Hao, David J Waxman
Sex-specific temporal patterns of pituitary GH secretion determine the sex-biased transcription of hundreds of genes in the liver and impart significant sex differences in liver physiology, metabolism and disease. Sex differences in hepatic gene expression vary widely, ranging from <2-fold to >1,000-fold in the mouse. Here, we use small RNA sequencing to discover 24 sex-biased mouse liver miRNAs, and then investigate the roles of two of these miRNAs in GH-regulated liver sex differences. Studies in pre-pubertal and young adult mice, and in mice where pituitary hormones are ablated or where sex-specific hepatic GH signaling is dysregulated, demonstrated that the male-biased miR-1948 and the female-biased miR-802 are both regulated by sex-specific pituitary GH secretory patterns, acquire sex specificity at puberty, and are dependent on the GH-activated transcription factor STAT5 for their sex-specific expression...
January 16, 2018: Endocrinology
https://www.readbyqxmd.com/read/29346292/isoform-sequencing-and-state-of-art-applications-for-unravelling-complexity-of-plant-transcriptomes
#12
REVIEW
Dong An, Hieu X Cao, Changsheng Li, Klaus Humbeck, Wenqin Wang
Single-molecule real-time (SMRT) sequencing developed by PacBio, also called third-generation sequencing (TGS), offers longer reads than the second-generation sequencing (SGS). Given its ability to obtain full-length transcripts without assembly, isoform sequencing (Iso-Seq) of transcriptomes by PacBio is advantageous for genome annotation, identification of novel genes and isoforms, as well as the discovery of long non-coding RNA (lncRNA). In addition, Iso-Seq gives access to the direct detection of alternative splicing, alternative polyadenylation (APA), gene fusion, and DNA modifications...
January 18, 2018: Genes
https://www.readbyqxmd.com/read/29344146/integrated-microrna-mrna-analyses-of-distinct-expression-profiles-in-follicular-thyroid-tumors
#13
Jiadong Chi, Xiangqian Zheng, Ming Gao, Jingzhu Zhao, Dapeng Li, Jiansen Li, Li Dong, Xianhui Ruan
MicroRNAs (miRNAs/miRs) are small non-coding RNAs identified in plants, animals and certain viruses; they function in RNA silencing and post-transcriptional regulation of gene expression. miRNAs also serve an important role in the pathogenesis, diagnosis and treatment of tumors. However, few studies have investigated the role of miRNAs in thyroid tumors. In the present study, the expression of miRNA and mRNA was compared between follicular thyroid carcinoma (FTC) and follicular thyroid adenoma (FA) samples, and then miRNA-mRNA regulatory network analysis was performed...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29343631/stochastic-resonances-in-a-distributed-genetic-broadcasting-system-the-nf%C3%AE%C2%BAb-i%C3%AE%C2%BAb-paradigm
#14
Zhipeng Wang, Davit A Potoyan, Peter G Wolynes
Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites...
January 2018: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/29342231/mapping-gene-regulatory-networks-from-single-cell-omics-data
#15
Mark W E J Fiers, Liesbeth Minnoye, Sara Aibar, Carmen Bravo González-Blas, Zeynep Kalender Atak, Stein Aerts
Single-cell techniques are advancing rapidly and are yielding unprecedented insight into cellular heterogeneity. Mapping the gene regulatory networks (GRNs) underlying cell states provides attractive opportunities to mechanistically understand this heterogeneity. In this review, we discuss recently emerging methods to map GRNs from single-cell transcriptomics data, tackling the challenge of increased noise levels and data sparsity compared with bulk data, alongside increasing data volumes. Next, we discuss how new techniques for single-cell epigenomics, such as single-cell ATAC-seq and single-cell DNA methylation profiling, can be used to decipher gene regulatory programmes...
January 12, 2018: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/29340052/gene-expression-profiling-and-construction-of-a-putative-gene-regulatory-network-of-bladder-cancer-tumor-initiating-cells
#16
Zhuoyuan Xin, Zhao Yang, Jianting Xu, Chaoying Li, Tong Shao, Guoqing Wang, Chong Li
Human bladder cancer tumors have been shown to contain a subpopulation of cells with stem-like characteristics that may trigger tumor growth, recurrence, and metastasis. These cells, known as tumor-initiating cells (TICs), would be effective diagnostic tools and valuable therapeutic targets. Here, we report the isolation of TICs from seven bladder cancer cell lines and show that TICs from different sources vary on their ability to form tumorspheres in vitro and generate xenografts in vivo, which suggest they are remarkably heterogeneous...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340016/mir-19-regulates-the-proliferation-and-invasion-of-glioma-by-runx3-via-%C3%AE-catenin-tcf-4-signaling
#17
Jikui Sun, Zhifan Jia, Banban Li, Anling Zhang, Guangxiu Wang, Peiyu Pu, Zhijuan Chen, Zengguang Wang, Weidong Yang
Accumulating data demonstrates that the network dysregulation of microRNA-medicated target genes is involved in glioma. We have previously found miR-19a/b overexpression in glioma cell lines and specimens with various tumour grades. However, there was no report on the function and regulatory mechanism of miR-19a/b in glioma. In this study, based on our previous research data, we first determine the inverse relationship between miR-19 (miR-19a and miR-19b) and RUNX3 which is also identified the reduced expression in tumour tissues by real-time PCR and IHC...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339519/evidence-for-convergent-evolution-of-sine-directed-staufen-mediated-mrna-decay
#18
Bronwyn A Lucas, Eitan Lavi, Lily Shiue, Hana Cho, Sol Katzman, Keita Miyoshi, Mikiko C Siomi, Liran Carmel, Manuel Ares, Lynne E Maquat
Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29339459/a-novel-two-component-system-of-streptococcus-sanguinis-affecting-functions-associated-with-viability-in-saliva-and-biofilm-formation
#19
Tarsila M Camargo, Rafael N Stipp, Lívia A Alves, Erika N Harth-Chu, José F Höfling, Renata O Mattos-Graner
Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, SptRS Ss , affecting S. sanguinis survival in saliva and biofilm formation. Isogenic mutants of sptRSs (SKsptR) and sptSSs (SKsptS) showed reduced cell counts in ex vivo assays of viability in saliva, compared to parent strain SK36 and complemented mutants. Reduced counts of the mutants in saliva were associated with reduced growth rates in poor nutrient medium (RPMI) and increased susceptibility to deposition of C3b and MAC of the complement system, a defense component of saliva and serum...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339339/proteomics-and-genetic-analyses-reveal-the-effects-of-arsenite-oxidation-on-metabolic-pathways-and-the-roles-of-aior-in-agrobacterium-tumefaciens-gw4
#20
Kaixiang Shi, Qian Wang, Xia Fan, Gejiao Wang
A heterotrophic arsenite [As(III)]-oxidizing bacterium Agrobacterium tumefaciens GW4 isolated from As(III)-rich groundwater sediment showed high As(III) resistance and could oxidize As(III) to As(V). The As(III) oxidation could generate energy and enhance growth, and AioR was the regulator for As(III) oxidase. To determine the related metabolic pathways mediated by As(III) oxidation and whether AioR regulated other cellular responses to As(III), isobaric tags for relative and absolute quantitation (iTRAQ) was performed in four treatments, GW4 (+AsIII)/GW4 (-AsIII), GW4-ΔaioR (+AsIII)/GW4-ΔaioR (-AsIII), GW4-ΔaioR (-AsIII)/GW4 (-AsIII) and GW4-ΔaioR (+AsIII)/GW4 (+AsIII)...
January 12, 2018: Environmental Pollution
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