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https://www.readbyqxmd.com/read/29053968/multiscale-3d-genome-rewiring-during-mouse-neural-development
#1
Boyan Bonev, Netta Mendelson Cohen, Quentin Szabo, Lauriane Fritsch, Giorgio L Papadopoulos, Yaniv Lubling, Xiaole Xu, Xiaodan Lv, Jean-Philippe Hugnot, Amos Tanay, Giacomo Cavalli
Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We comprehensively mapped 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest-resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating TAD boundaries de novo...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29053796/exome-sequencing-and-network-analysis-identifies-shared-mechanisms-underlying-spinocerebellar-ataxia
#2
Esther A R Nibbeling, Anna Duarri, Corien C Verschuuren-Bemelmans, Michiel R Fokkens, Juha M Karjalainen, Cleo J L M Smeets, Jelkje J de Boer-Bergsma, Gerben van der Vries, Dennis Dooijes, Giovana B Bampi, Cleo van Diemen, Ewout Brunt, Elly Ippel, Berry Kremer, Monique Vlak, Noam Adir, Cisca Wijmenga, Bart P C van de Warrenburg, Lude Franke, Richard J Sinke, Dineke S Verbeek
The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here, we report five novel spinocerebellar ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a combination of exome sequencing in genetically undiagnosed families and targeted resequencing of exome candidates in a cohort of singletons...
October 6, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29053464/co-expression-network-approach-to-studying-the-effects-of-botulinum-neurotoxin-a
#3
Kavitha Mukund, Samuel R Ward, Richard L Lieber, Shankar Subramaniam
Botulinum Neurotoxin A (BoNT-A) is a potent neurotoxin with several clinical applications.The goal of this study was to utilize co-expression network theory to analyze temporal transcriptional data from skeletal muscle after BoNT-A treatment. Expression data for 2000 genes (extracted using a ranking heuristic) served as the basis for this analysis. Using weighted gene co-expression network analysis (WGCNA), we identified 19 co-expressed modules, further hierarchically clustered into 5 groups. Quantifying average expression and co-expression patterns across these groups revealed temporal aspects of muscle's response to BoNT-A...
October 16, 2017: IEEE/ACM Transactions on Computational Biology and Bioinformatics
https://www.readbyqxmd.com/read/29053381/adaptive-networkprofiler-for-identifying-cancer-characteristic-specific-gene-regulatory-networks
#4
Heewon Park, Teppei Shimamura, Seiya Imoto, Satoru Miyano
There is currently much discussion about sample (patient)-specific gene regulatory network identification, since the efficiently constructed sample-specific gene networks lead to effective personalized cancer therapy. Although statistical approaches have been proposed for inferring gene regulatory networks, the methods cannot reveal sample-specific characteristics because the existing methods, such as an L1-type regularization, provide averaged results for all samples. Thus, we cannot reveal sample-specific characteristics in transcriptional regulatory networks...
October 20, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/29052199/identification-of-in-planta-protein-protein-interactions-using-ip-ms
#5
Suraj Jamge, Gerco C Angenent, Marian Bemer
Gene regulation by transcription factors involves complex protein interaction networks, which include chromatin remodeling and modifying proteins as an integral part. Decoding these protein interactions is crucial for our understanding of chromatin-mediated gene regulation. Here, we describe a method for the immunoprecipitation of in planta nuclear protein complexes followed by mass spectrometry (IP-MS) to identify interactions between transcription factors and chromatin remodelers/modifiers in plants. In addition to a step-by-step bench protocol for immunoprecipitation and subsequent mass spectrometry, we provide guidelines and pointers on necessary controls and data analysis approaches...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29051820/vqmapkkk38-is-essential-for-stilbene-accumulation-in-grapevine
#6
Yuntong Jiao, Dan Wang, Lan Wang, Changyue Jiang, Yuejin Wang
Vitis species, including grapevine, produce a class of secondary metabolites called stilbenes that are important for plant disease resistance and can have positive effects on human health. Mitogen-activated protein kinase (MAPK) signaling cascades not only play key roles in plant defense responses but also contribute to stilbene biosynthesis in grapevine. MAPKKKs function at the upper level of the MAPK network and initiate signaling through this pathway. In this study, a Raf-like MAPKKK gene, VqMAPKKK38, was identified and functionally characterized from the Chinese wild grapevine V...
2017: Horticulture Research
https://www.readbyqxmd.com/read/29051608/transcription-factors-and-stress-response-gene-alterations-in-human-keratinocytes-following-solar-simulated-ultra-violet-radiation
#7
Thomas L Des Marais, Thomas Kluz, Dazhong Xu, Xiaoru Zhang, Lisa Gesumaria, Mary S Matsui, Max Costa, Hong Sun
Ultraviolet radiation (UVR) from sunlight is the major effector for skin aging and carcinogenesis. However, genes and pathways altered by solar-simulated UVR (ssUVR), a mixture of UVA and UVB, are not well characterized. Here we report global changes in gene expression as well as associated pathways and upstream transcription factors in human keratinocytes exposed to ssUVR. Human HaCaT keratinocytes were exposed to either a single dose or 5 repetitive doses of ssUVR. Comprehensive analyses of gene expression profiles as well as functional annotation were performed at 24 hours post irradiation...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051564/network-analysis-of-emt-and-met-micro-rna-regulation-in-breast-cancer
#8
Diana Drago-García, Jesús Espinal-Enríquez, Enrique Hernández-Lemus
Over the last years, microRNAs (miRs) have shown to be crucial for breast tumour establishment and progression. To understand the influence that miRs have over transcriptional regulation in breast cancer, we constructed mutual information networks from 86 TCGA matched breast invasive carcinoma and control tissue RNA-Seq and miRNA-Seq sequencing data. We show that miRs are determinant for tumour and control data network structure. In tumour data network, miR-200, miR-199 and neighbour miRs seem to cooperate on the regulation of the acquisition of epithelial and mesenchymal traits by the biological processes: Epithelial-Mesenchymal Transition (EMT) and Mesenchymal to Epithelial Transition (MET)...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051502/comparative-transcriptomics-reveal-developmental-turning-points-during-embryogenesis-of-a-hemimetabolous-insect-the-damselfly-ischnura-elegans
#9
Sabrina Simon, Sven Sagasser, Edoardo Saccenti, Mercer R Brugler, M Eric Schranz, Heike Hadrys, George Amato, Rob DeSalle
Identifying transcriptional changes during embryogenesis is of crucial importance for unravelling evolutionary, molecular and cellular mechanisms that underpin patterning and morphogenesis. However, comparative studies focusing on early/embryonic stages during insect development are limited to a few taxa. Drosophila melanogaster is the paradigm for insect development, whereas comparative transcriptomic studies of embryonic stages of hemimetabolous insects are completely lacking. We reconstructed the first comparative transcriptome covering the daily embryonic developmental progression of the blue-tailed damselfly Ischnura elegans (Odonata), an ancient hemimetabolous representative...
October 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29051499/an-integrative-method-to-decode-regulatory-logics-in-gene-transcription
#10
Bin Yan, Daogang Guan, Chao Wang, Junwen Wang, Bing He, Jing Qin, Kenneth R Boheler, Aiping Lu, Ge Zhang, Hailong Zhu
Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF-TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs...
October 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/29050232/progressive-modulation-of-the-human-olfactory-bulb-transcriptome-during-alzheimer%C3%A2-s-disease-evolution-novel-insights-into-the-olfactory-signaling-across-proteinopathies
#11
Mercedes Lachen-Montes, María Victoria Zelaya, Víctor Segura, Joaquín Fernández-Irigoyen, Enrique Santamaría
Alzheimer´s disease (AD) is characterized by progressive dementia, initially presenting olfactory dysfunction. Despite the olfactory bulb (OB) is the first central structure of the olfactory pathway, we lack a complete molecular characterization of the transcriptional events that occurs in this olfactory area during AD progression. To address this gap in knowledge, we have assessed the genome-wide expression in postmortem OBs from subjects with varying degree of AD pathology. A stage-dependent deregulation of specific pathways was observed, revealing transmembrane transport, and neuroinflammation as part of the functional modules that are disrupted across AD grading...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29049853/nutrient-driven-o-glcnac-in-proteostasis-and-neurodegeneration
#12
REVIEW
Ilhan Akan, Stephanie Olivier-Van Stichelen, Michelle R Bond, John A Hanover
Proteostasis is essential in the mammalian brain where post-mitotic cells must function for decades to maintain synaptic contacts and memory. The brain is dependent on glucose and other metabolites for proper function and is spared from metabolic deficits even during starvation. In this review, we outline how the nutrient sensitive nucleocytoplasmic posttranslational modification O-linked N-acetylglucosamine (O-GlcNAc) regulates protein homeostasis. The O-GlcNAc modification is highly abundant in the mammalian brain, and has been linked to proteopathies, including neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's...
October 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29049397/the-transcriptional-regulator-lysg-rv1985c-of-mycobacterium-tuberculosis-activates-lyse-rv1986-in-a-lysine-dependent-manner
#13
Marie Schneefeld, Tobias Busche, Robert Geffers, Jörn Kalinowski, Franz-Christoph Bange
The Mycobacterium tuberculosis protein encoded by the Rv1986 gene is a target for memory T cells in patients with tuberculosis, and shows strong similarities to a lysine exporter LysE of Corynebacterium glutamicum. During infection, the pathogen Mycobacterium tuberculosis adapts its metabolism to environmental changes. In this study, we found that the expression of Rv1986 is controlled by Rv1985c. Rv1985c is located directly upstream of Rv1986 with an overlapping promoter region between both genes. Semiquantitative reverse transcription PCR using an isogenic mutant of Mycobacterium tuberculosis lacking Rv1985c showed that in the presence of lysine, Rv1985c protein positively upregulated the expression of Rv1986...
2017: PloS One
https://www.readbyqxmd.com/read/29049183/identifying-key-genes-associated-with-acute-myocardial-infarction
#14
Ming Cheng, Shoukuan An, Junquan Li
BACKGROUND: This study aimed to identify key genes associated with acute myocardial infarction (AMI) by reanalyzing microarray data. METHODS: Three gene expression profile datasets GSE66360, GSE34198, and GSE48060 were downloaded from GEO database. After data preprocessing, genes without heterogeneity across different platforms were subjected to differential expression analysis between the AMI group and the control group using metaDE package. P < .05 was used as the cutoff for a differentially expressed gene (DEG)...
October 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29046998/metabolite-profiling-and-associated-gene-expression-reveal-two-metabolic-shifts-during-the-seed-to-seedling-transition-in-arabidopsis-thaliana
#15
Anderson Tadeu Silva, Wilco Ligterink, Henk W M Hilhorst
Metabolic and transcriptomic correlation analysis identified two distinctive profiles involved in the metabolic preparation for seed germination and seedling establishment, respectively. Transcripts were identified that may control metabolic fluxes. The transition from a quiescent metabolic state (dry seed) to the active state of a vigorous seedling is crucial in the plant's life cycle. We analysed this complex physiological trait by measuring the changes in primary metabolism that occur during the transition in order to determine which metabolic networks are operational...
October 18, 2017: Plant Molecular Biology
https://www.readbyqxmd.com/read/29046873/embryonic-stem-cell-like-subpopulations-in-venous-malformation
#16
Elysia M S Tan, Sam Duro Siljee, Helen D Brasch, Susana Enriquez, Swee T Tan, Tinte Itinteang
BACKGROUND: Venous malformation (VM) consists of a network of ectatic anomalous thin-walled venous channels. A role for an activating TIE2 mutation in the development of the dilated luminal vessels in VM, and its proposed involvement of embryonic stem cells (ESCs), led us to investigate the expression of ESC markers in subcutaneous VM (SCVM) and intramuscular VM (IMVM). METHODS: Formalin-fixed paraffin-embedded sections of SCVM from seven patients and IMVM samples from seven patients were analyzed for the expression of Nanog, pSTAT3, OCT4, SOX2, SALL4, and CD44, using 3,3'-diaminobenzidine (DAB) immunohistochemical (IHC) staining...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29046437/modulation-of-global-transcriptional-regulatory-networks-as-a-strategy-for-increasing-kanamycin-resistance-of-the-translational-elongation-factor-g-mutants-in-escherichia-coli
#17
Aalap Mogre, Reshma T V, Aswin Sai Narain Seshasayee
Evolve and resequence experiments have provided us a tool to understand bacterial adaptation to antibiotics. In our previous work, we had used short term evolution to isolate mutants resistant to the ribosome targeting antibiotic kanamycin, and reported that Escherichia coli develops low cost resistance to kanamycin via  different point mutations in the translation Elongation Factor-G (EF-G). Furthermore, we had shown that the resistance of EF-G mutants could be increased by second site mutations in the genes rpoD / cpxA / topA / cyaA Mutations in three of these genes had been discovered in earlier screens for aminoglycoside resistance...
October 18, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29046401/reconstructing-the-molecular-function-of-genetic-variation-in-regulatory-networks
#18
Roni Wilentzik, Chun Jimmie Ye, Irit Gat-Viks
During the past decade, genetic studies have recognized hundreds of polymorphic DNA loci ('reQTLs') as potential contributors to inter-individual variation in transcriptional response to stimulations. Such reQTLs commonly affect the transduction of signals along the regulatory network that controls gene transcription. Identifying the pathways through which reQTLs perturb the underlying network has been a major challenge. Here we present GEVIN, a methodology that simultaneously identifies a reQTL and the particular pathway at which the reQTL affects downstream signal transduction along the network...
October 18, 2017: Genetics
https://www.readbyqxmd.com/read/29046293/exercise-induces-tfeb-expression-and-activity-in-skeletal-muscle-in-a-pgc-1%C3%AE-dependent-manner
#19
Avigail T Erlich, Diane M Brownlee, Kaitlyn Beyfuss, David A Hood
The mitochondrial network in muscle is controlled by the opposing processes of mitochondrial biogenesis and mitophagy. The coactivator PGC-1α regulates biogenesis, while the transcription of mitophagy-related genes is controlled by transcription factor EB (TFEB). PGC-1α activation is induced with exercise, however the effect of exercise on TFEB is not fully known. We investigated the interplay between PGC-1α and TFEB on mitochondria in response to acute contractile activity in C2C12 myotubes, and following exercise in WT and PGC-1α KO mice...
October 18, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29045833/intestinal-fork-head-regulates-nutrient-absorption-and-promotes-longevity
#20
Ekin Bolukbasi, Mobina Khericha, Jennifer C Regan, Dobril K Ivanov, Jennifer Adcott, Miranda C Dyson, Tobias Nespital, Janet M Thornton, Nazif Alic, Linda Partridge
Reduced activity of nutrient-sensing signaling networks can extend organismal lifespan, yet the underlying biology remains unclear. We show that the anti-aging effects of rapamycin and reduced intestinal insulin/insulin growth factor (IGF) signaling (IIS) require the Drosophila FoxA transcription factor homolog Fork Head (FKH). Intestinal FKH induction extends lifespan, highlighting a role for the gut. FKH binds to and is phosphorylated by AKT and Target of Rapamycin. Gut-specific FKH upregulation improves gut barrier function in aged flies...
October 17, 2017: Cell Reports
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