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https://www.readbyqxmd.com/read/29351168/co-regulation-of-er-stress-and-oxidative-stress-in-neuropathic-pain-and-disinhibition-of-the-spinal-nociceptive-circuitry
#1
Yanhu Ge, Yingfu Jiao, Peiying Li, Zhenghua Xiang, Zhi Li, Long Wang, Wenqian Li, Hao Gao, Jiayun Shao, Daxiang Wen, Weifeng Yu
The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen leads to ER stress, which is related to cellular reactive oxygen species (ROS) production. Neuropathic pain may result from spinal dorsal horn (SDH) ER stress. In this study, we examined the cause-effect relationship between ER stress and neuropathic pain using the spinal nerve ligation(SNL) rat model. We showed that ER stress was mutually promotive with oxidative stress during the process. We also tested the hypothesis that spinal sensitization arose from reduced activities of GABA-ergic interneurons and that spinal sensitization was mediated by SDH ER stress...
January 18, 2018: Pain
https://www.readbyqxmd.com/read/29348663/enhancer-associated-long-non-coding-rna-leene-regulates-endothelial-nitric-oxide-synthase-and-endothelial-function
#2
Yifei Miao, Nassim E Ajami, Tse-Shun Huang, Feng-Mao Lin, Chih-Hong Lou, Yun-Ting Wang, Shuai Li, Jian Kang, Hannah Munkacsi, Mano R Maurya, Shakti Gupta, Shu Chien, Shankar Subramaniam, Zhen Chen
The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE)...
January 18, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348434/identification-of-genetic-elements-in-metabolism-by-high-throughput-mouse-phenotyping
#3
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/29346778/diverse-brain-myeloid-expression-profiles-reveal-distinct-microglial-activation-states-and-aspects-of-alzheimer-s-disease-not-evident-in-mouse-models
#4
Brad A Friedman, Karpagam Srinivasan, Gai Ayalon, William J Meilandt, Han Lin, Melanie A Huntley, Yi Cao, Seung-Hye Lee, Patrick C G Haddick, Hai Ngu, Zora Modrusan, Jessica L Larson, Joshua S Kaminker, Marcel P van der Brug, David V Hansen
Microglia, the CNS-resident immune cells, play important roles in disease, but the spectrum of their possible activation states is not well understood. We derived co-regulated gene modules from transcriptional profiles of CNS myeloid cells of diverse mouse models, including new tauopathy model datasets. Using these modules to interpret single-cell data from an Alzheimer's disease (AD) model, we identified microglial subsets-distinct from previously reported "disease-associated microglia"-expressing interferon-related or proliferation modules...
January 16, 2018: Cell Reports
https://www.readbyqxmd.com/read/29346402/gene-regulation-in-kluyveromyces-marxianus-in-the-context-of-chromosomes
#5
Du Toit W P Schabort, Stephanus G Kilian, James C du Preez
Eukaryotes, including the unicellular eukaryotes such as yeasts, employ multiple levels of gene regulation. Regulation of chromatin structure through chromatin compaction cascades, and influenced by transcriptional insulators, might play a role in the coordinated regulation of genes situated at adjacent loci and expressed as a co-regulated cluster. Subtelomeric gene silencing, which has previously been described in the yeast Saccharomyces cerevisiae, is an example of this phenomenon. Transcription from a common regulatory element located around a shared intergenic region is another factor that could coordinate the transcription of genes at adjacent loci...
2018: PloS One
https://www.readbyqxmd.com/read/29343207/genome-wide-analysis-identified-a-number-of-dysregulated-long-noncoding-rna-lncrna-in-human-pancreatic-ductal-adenocarcinoma
#6
Sijie Hao, Lie Yao, Jiaxin Huang, Hang He, Feng Yang, Yang Di, Chen Jin, Deliang Fu
BACKGROUND: Long noncoding RNAs have been shown to play crucial roles in cancer biology, while the long noncoding RNA landscapes of pancreatic ductal adenocarcinoma have not been completely characterized. We aimed to determine whether long noncoding RNA could serve as early diagnostic biomarkers for pancreatic ductal adenocarcinoma. METHOD: We conducted a genome-wide microarray analysis on pancreatic ductal adenocarcinoma and their adjacent noncancerous tissues from 8 Chinese patients...
January 1, 2018: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29335020/ensemble-genomic-analysis-in-human-lung-tissue-identifies-novel-genes-for-chronic-obstructive-pulmonary-disease
#7
Jarrett D Morrow, Michael H Cho, John Platig, Xiaobo Zhou, Dawn L DeMeo, Weiliang Qiu, Bartholome Celli, Nathaniel Marchetti, Gerard J Criner, Raphael Bueno, George R Washko, Kimberly Glass, John Quackenbush, Edwin K Silverman, Craig P Hersh
BACKGROUND: Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) significantly associated with chronic obstructive pulmonary disease (COPD). However, many genetic variants show suggestive evidence for association but do not meet the strict threshold for genome-wide significance. Integrative analysis of multiple omics datasets has the potential to identify novel genes involved in disease pathogenesis by leveraging these variants in a functional, regulatory context...
January 15, 2018: Human Genomics
https://www.readbyqxmd.com/read/29330297/characterization-and-evidence-of-the-mir-888-cluster-as-a-novel-cancer-network-in-prostate
#8
Tsuyoshi Hasegawa, Garrison Glavich, Mary Pahuski, Aleena M Short, Oliver John Semmes, Lifang Yang, Vitold Galkin, Richard R Drake, Aurora Esquela-Kerscher
Prostate cancer afflicts 1 in 7 men and is the second leading cause of male cancer-related deaths in the United States. MicroRNAs (miRNAs), an extensive class of ~22 nucleotide non-coding RNAs, are often aberrantly expressed in tissues and fluids from prostate cancer patients but the mechanism of how specific miRNAs regulate prostate tumorigenesis and metastasis are poorly understood. Here, miR-888 was identified as a novel prostate factor that promotes proliferation and migration. miR-888 resides within a genomic cluster of 7 miRNA genes (mir-892c, mir-890, mir-888, mir-892a, mir-892b, mir-891b, mir-891a) on human chromosome Xq27...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29323242/adipose-specific-lipin1-overexpression-in-mice-protects-against-alcohol-induced-liver-injury
#9
Wenliang Zhang, Wei Zhong, Qian Sun, Xinguo Sun, Zhanxiang Zhou
Excessive fatty acid release from the white adipose tissue (WAT) contributes to the development of alcoholic liver disease (ALD). Lipin1 (LPIN1), as a co-regulator of DNA-bound transcription factors and a phosphatidic acid (PA) phosphatase (PAP) enzyme that dephosphorylates PA to form diacylglycerol (DAG), is dramatically reduced by alcohol in the WAT. This study aimed at determining the role of adipose LPIN1 in alcohol-induced lipodystrophy and the development of ALD. Transgenic mice overexpressing LPIN1 in adipose tissue (LPIN1-Tg) and wild type (WT) mice were fed a Lieber-DeCarli alcohol or isocaloric maltose dextrin control liquid diet for 8 weeks...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317749/determining-direct-binders-of-the-androgen-receptor-using-a-high-throughput-cellular-thermal-shift-assay
#10
Joseph Shaw, Mathew Leveridge, Charlotta Norling, Jakob Karén, Daniel Martinez Molina, Daniel O'Neill, James E Dowling, Paul Davey, Suzanna Cowan, Michael Dabrowski, Martin Main, Davide Gianni
Androgen Receptor (AR) is a key driver in prostate cancer. Direct targeting of AR has valuable therapeutic potential. However, the lack of disease relevant cellular methodologies capable of discriminating between inhibitors that directly bind AR and those that instead act on AR co-regulators has made identification of novel antagonists challenging. The Cellular Thermal Shift Assay (CETSA) is a technology enabling confirmation of direct target engagement with label-free, endogenous protein in living cells. We report the development of the first high-throughput CETSA assay (CETSA HT) to identify direct AR binders in a prostate cancer cell line endogenously expressing AR...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313809/parp1-facilitates-ep300-recruitment-to-the-promoters-of-the-subset-of-rbl2-dependent-genes
#11
Agnieszka Robaszkiewicz, Ewelina Wiśnik, Zsolt Regdon, Kinga Chmielewska, László Virág
Differentiation of human monocytes is associated with proliferation arrest resulting from activation of the inter alia retinoblastoma protein family of gene repressors, which target gene promoters in an E2F-dependent manner. To investigate RBL2 contribution to defining monocyte phenotype and function, we used primer libraries. We identified genes encoding two surface receptors (CXCR1 and IL17RE) and two TLR signaling mediators (CD86 and NFKB2) that are repressed by the RBL2-E2F4-HDAC1-BRM complex. Surprisingly, PARP1 co-regulated 24 out of the 28 identified genes controlled by RBL2...
December 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29301495/cattle-infection-response-network-and-its-functional-modules
#12
Hamid Beiki, Abbas Pakdel, Ardeshir Nejati Javaremi, Ali Masoudi-Nejad, James M Reecy
BACKGROUND: Weighted Gene Co-expression Network analysis, a powerful technique used to extract co-expressed gene pattern from mRNA expression data, was constructed to infer common immune strategies used by cattle in response to five different bacterial species (Escherichia coli, Mycobacterium avium, Mycobacterium bovis, Salmonella and Staphylococcus aureus) and a protozoa (Trypanosoma Congolense) using 604 publicly available gene expression microarrays from 12 cattle infection experiments...
January 5, 2018: BMC Immunology
https://www.readbyqxmd.com/read/29288621/arabidopsis-acyl-coa-binding-protein1-interacts-with-sterol-c4-methyl-oxidase1-2-to-modulate-gene-expression-of-homeodomain-leucine-zipper-iv-transcription-factors
#13
Shiu-Cheung Lung, Pan Liao, Edward C Yeung, An-Shan Hsiao, Yan Xue, Mee-Len Chye
Fatty acids (FAs) and sterols constitute building blocks of eukaryotic membranes and lipid signals. Co-regulation of FA and sterol synthesis is mediated by sterol regulatory element-binding proteins in animals but remains elusive in plants. We reported recently that Arabidopsis ACYL-COA-BINDING PROTEIN1 (ACBP1) modulates sterol synthesis via protein-protein interaction with STEROL C4-METHYL OXIDASE1-1 (SMO1-1). Herein, ACBP1 was demonstrated to co-express and interact with SMO1-2 by yeast two-hybrid, co-localization, pull-down, co-immunoprecipitation and β-glucuronidase assays...
December 30, 2017: New Phytologist
https://www.readbyqxmd.com/read/29288409/gene-expression-analysis-to-identify-mechanisms-underlying-heart-failure-susceptibility-in-mice-and-humans
#14
Christoph Koentges, Mark E Pepin, Carolyn Müsse, Katharina Pfeil, Sonia V Viteri Alvarez, Natalie Hoppe, Michael M Hoffmann, Katja E Odening, Samuel Sossalla, Andreas Zirlik, Lutz Hein, Christoph Bode, Adam R Wende, Heiko Bugger
Genetic factors are known to modulate cardiac susceptibility to ventricular hypertrophy and failure. To determine how strain influences the transcriptional response to pressure overload-induced heart failure (HF) and which of these changes accurately reflect the human disease, we analyzed the myocardial transcriptional profile of mouse strains with high (C57BL/6J) and low (129S1/SvImJ) susceptibility for HF development, which we compared to that of human failing hearts. Following transverse aortic constriction (TAC), C57BL/6J mice developed overt HF while 129S1/SvImJ did not...
December 29, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29284404/multiple-functions-of-creb-binding-protein-during-postembryonic-development-identification-of-target-genes
#15
Amit Roy, Smitha George, Subba Reddy Palli
BACKGROUND: Juvenile hormones (JH) and ecdysteroids control postembryonic development in insects. They serve as valuable targets for pest management. Hence, understanding the molecular mechanisms of their action is of crucial importance. CREB-binding protein (CBP) is a universal transcriptional co-regulator. It controls the expression of several genes including those from hormone signaling pathways through co-activation of many transcription factors. However, the role of CBP during postembryonic development in insects is not well understood...
December 29, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29275167/abscisic-acid-signaling-inhibits-brassinosteroid-signaling-through-dampening-the-dephosphorylation-of-bin2-by-abi1-and-abi2
#16
Haijiao Wang, Jie Tang, Jing Liu, Jin Hu, Jingjing Liu, Yuxiao Chen, Zhenying Cai, Xuelu Wang
Abscisic acid (ABA) and brassinosteroid (BR) antagonistically regulate many aspects of plant growth and development. A physiological study revealed that the inhibition of BR signaling by ABA is largely dependent on ABI1 and ABI2, but genetic and molecular evidence is lacking. In the BR signaling, their crosstalk occurs after BR receptor complex, but upstream of BIN2. However, which components act as the hub to directly mediate their crosstalk has remains a big mystery. Here, we found that ABI1 and ABI2 interact with BIN2, and dephosphorylate BIN2 to regulate its activity on the phosphorylation of BES1...
December 21, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29275164/genome-wide-analysis-of-transcriptional-variability-in-a-large-maize-teosinte-population
#17
Xufeng Wang, Qiuyue Chen, Yaoyao Wu, Zachary H Lemmon, Guanghui Xu, Cheng Huang, Yameng Liang, Dingyi Xu, Dan Li, John F Doebley, Feng Tian
The regulation of gene expression plays an important role in controlling plant phenotypes and adaptation. Here, we report a comprehensive assessment of gene expression variation by sequencing the transcriptome of a large maize-teosinte experimental population. Genome-wide mapping identified 25,660 expression quantitative trait loci (eQTL) for 17,311 genes, capturing an unprecedented range of expression variation. We found that local-eQTL more frequently mapped to adjacent genes, displaying a mode of expression piggybacking, which consequently created co-regulated gene clusters...
December 21, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29273203/transcriptome-wide-identification-and-validation-of-interactions-between-the-mirna-machinery-and-hur-on-mrna-targets
#18
Yahui Li, Jason A Estep, Fedor V Karginov
The 3' UTR of mRNAs is the primary regulatory region that mediates post-transcriptional control by microRNAs and RNA-binding proteins (RBPs) in the cytoplasm. Aside from individual sequence-specific binding and regulation, examples of interaction between these factors at particular 3' UTR sites have emerged. However, the whole picture of such higher-order regulatory modules across the transcriptome is lacking. Here, we investigate the interactions between HuR, a ubiquitous RBP, and Ago2, a core effector of the miRNA pathway, at the transcriptome-wide level...
December 20, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29273066/co-regulation-of-transcription-by-brg1-and-brm-two-mutually-exclusive-swi-snf-atpase-subunits
#19
Jesse R Raab, John S Runge, Camarie C Spear, Terry Magnuson
BACKGROUND: SWI/SNF is a large heterogeneous multi-subunit chromatin remodeling complex. It consists of multiple sets of mutually exclusive components. Understanding how loss of one sibling of a mutually exclusive pair affects the occupancy and function of the remaining complex is needed to understand how mutations in a particular subunit might affect tumor formation. Recently, we showed that the members of the ARID family of SWI/SNF subunits (ARID1A, ARID1B and ARID2) had complex transcriptional relationships including both antagonism and cooperativity...
December 22, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29249668/gcn5-regulates-fgf-signaling-and-activates-selective-myc-target-genes-during-early-embryoid-body-differentiation
#20
Li Wang, Evangelia Koutelou, Calley Hirsch, Ryan McCarthy, Andria Schibler, Kevin Lin, Yue Lu, Collene Jeter, Jianjun Shen, Michelle C Barton, Sharon Y R Dent
Precise control of gene expression during development is orchestrated by transcription factors and co-regulators including chromatin modifiers. How particular chromatin-modifying enzymes affect specific developmental processes is not well defined. Here, we report that GCN5, a histone acetyltransferase essential for embryonic development, is required for proper expression of multiple genes encoding components of the fibroblast growth factor (FGF) signaling pathway in early embryoid bodies (EBs). Gcn5-/- EBs display deficient activation of ERK and p38, mislocalization of cytoskeletal components, and compromised capacity to differentiate toward mesodermal lineage...
December 12, 2017: Stem Cell Reports
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