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Expression genomic integration

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https://www.readbyqxmd.com/read/27913844/global-dna-methylation-profiling-of-manganese-exposed-human-neuroblastoma-sh-sy5y-cells-reveals-epigenetic-alterations-in-parkinson-s-disease-associated-genes
#1
Prashant Tarale, Saravanadevi Sivanesan, Atul P Daiwile, Reinhard Stöger, Amit Bafana, Pravin K Naoghare, Devendra Parmar, Tapan Chakrabarti, Krishnamurthi Kannan
Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson's disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson's disease...
December 2, 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#2
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27911271/immunoglobulin-superfamily-genes-are-novel-prognostic-biomarkers-for-breast-cancer
#3
Yue Li, Maoni Guo, Zhenkun Fu, Peng Wang, Yan Zhang, Yue Gao, Ming Yue, Shangwei Ning, Dianjun Li
Breast cancer progression is associated with dysregulated expression of the immunoglobulin superfamily (IgSF) genes that are involved in cell-cell recognition, binding and adhesion. Despite widespread evidence that many IgSF genes could serve as effective biomarkers, this potential has not been realized because the studies have focused mostly on individual genes and not the entire network. To gain a global perspective of the IgSF-related biomarkers, we constructed an IgSF-directed neighbor network (IDNN) and an IgSF-directed driver network (IDDN) by integrating multiple levels of data, including IgSF genes, breast cancer driver genes, protein-protein interaction (PPI) networks and gene expression profiling data...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27909336/c-terminal-truncated-hbv-x-promotes-hepato-oncogenesis-through-inhibition-of-tumor-suppressive-%C3%AE-catenin-bambi-signaling
#4
Seok Lee, Mi-Jin Lee, Jun Zhang, Goung-Ran Yu, Dae-Ghon Kim
C-terminal-truncated hepatitis B virus (HBV) X (HBx) (ctHBX) is frequently detected in hepatocellular carcinoma (HCC) through HBV integration into the host genome. However, the molecular mechanisms underlying ctHBx-associated oncogenic signaling have not yet been clarified. To elucidate the biological role of ctHBx in hepato-oncogenesis, we functionally analyzed ctHBx-mediated regulation of the activin membrane-bound inhibitor bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) through transforming growth factor-β (TGF-β) or β-catenin (CTNNB1) in HCC cells and in an animal model, and we compared its role to that of the full-length HBx protein...
December 2, 2016: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/27909306/rpl5-on-1p22-1-is-recurrently-deleted-in-multiple-myeloma-and-its-expression-is-linked-to-bortezomib-response
#5
I J F Hofman, M Van Duin, E De Bruyne, L Fancello, G Mulligan, E Geerdens, E Garelli, C Mancini, H Lemmens, M Delforge, P Vandenberghe, I Wlodarska, A Aspesi, L Michaux, K Vanderkerken, P Sonneveld, K De Keersmaecker
Chromosomal region 1p22 is deleted in ⩾20% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27907895/mutlbsgenedb-mutated-ligand-binding-site-gene-database
#6
Pora Kim, Junfei Zhao, Pinyi Lu, Zhongming Zhao
Mutations at the ligand binding sites (LBSs) can influence protein structure stability, binding affinity with small molecules, and drug resistance in cancer patients. Our recent analysis revealed that ligand binding residues had a significantly higher mutation rate than other parts of the protein. Here, we built mutLBSgeneDB (mutated Ligand Binding Site gene DataBase) available at http://zhaobioinfo.org/mutLBSgeneDB We collected and curated over 2300 genes (mutLBSgenes) having ∼12 000 somatic mutations at ∼10 000 LBSs across 16 cancer types and selected 744 drug targetable genes (targetable_mutLBSgenes) by incorporating kinases, transcription factors, pharmacological genes, and cancer driver genes...
October 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27907891/analysis-of-translation-using-polysome-profiling
#7
Héloïse Chassé, Sandrine Boulben, Vlad Costache, Patrick Cormier, Julia Morales
During the past decade, there has been growing interest in the role of translational regulation of gene expression in many organisms. Polysome profiling has been developed to infer the translational status of a specific mRNA species or to analyze the translatome, i.e. the subset of mRNAs actively translated in a cell. Polysome profiling is especially suitable for emergent model organisms for which genomic data are limited. In this paper, we describe an optimized protocol for the purification of sea urchin polysomes and highlight the critical steps involved in polysome purification...
October 7, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27907186/inter-tissue-gene-co-expression-networks-between-metabolically-healthy-and-unhealthy-obese-individuals
#8
Lisette J A Kogelman, Jingyuan Fu, Lude Franke, Jan Willem Greve, Marten Hofker, Sander S Rensen, Haja N Kadarmideen
BACKGROUND: Obesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10-25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development...
2016: PloS One
https://www.readbyqxmd.com/read/27907029/long-term-stable-and-tightly-controlled-expression-of-recombinant-proteins-in-antibiotics-free-conditions
#9
Soo-Jin Yeom, Dae-Hee Lee, Yu Jung Kim, Jeongmin Lee, Kil Koang Kwon, Gui Hwan Han, Haseong Kim, Hak-Sung Kim, Seung-Goo Lee
Plasmid-based gene expression is a fundamental tool in the field of biotechnology. However, overexpression of genes of interest with multi-copy plasmids often causes detrimental effects on host cells. To overcome this problem, chromosomal integration of target genes has been used for decades; however, insufficient protein expression occurred with this method. In this study, we developed a novel cloning and expression system named the chromosomal vector (ChroV) system, that has features of stable and high expression of target genes on the F' plasmid in the Escherichia coli JM109(DE3) strain...
2016: PloS One
https://www.readbyqxmd.com/read/27906459/integrative-genomic-analysis-identifies-ancestry-related-expression-quantitative-trait-loci-on-dna-polymerase-%C3%AE-and-supports-the-association-of-genetic-ancestry-with-survival-disparities-in-head-and-neck-squamous-cell-carcinoma
#10
Meganathan P Ramakodi, Karthik Devarajan, Elizabeth Blackman, Denise Gibbs, Danièle Luce, Jacqueline Deloumeaux, Suzy Duflo, Jeffrey C Liu, Ranee Mehra, Rob J Kulathinal, Camille C Ragin
BACKGROUND: African Americans with head and neck squamous cell carcinoma (HNSCC) have a lower survival rate than whites. This study investigated the functional importance of ancestry-informative single-nucleotide polymorphisms (SNPs) in HNSCC and also examined the effect of functionally important genetic elements on racial disparities in HNSCC survival. METHODS: Ancestry-informative SNPs, RNA sequencing, methylation, and copy number variation data for 316 oral cavity and laryngeal cancer patients were analyzed across 178 DNA repair genes...
December 1, 2016: Cancer
https://www.readbyqxmd.com/read/27906112/chromatin-wide-and-transcriptome-profiling-integration-uncovers-p38%C3%AE-mapk-as-a-global-regulator-of-skeletal-muscle-differentiation
#11
Jessica Segalés, Abul B M M K Islam, Roshan Kumar, Qi-Cai Liu, Pedro Sousa-Victor, F Jeffrey Dilworth, Esteban Ballestar, Eusebio Perdiguero, Pura Muñoz-Cánoves
BACKGROUND: Extracellular stimuli induce gene expression responses through intracellular signaling mediators. The p38 signaling pathway is a paradigm of the mitogen-activated protein kinase (MAPK) family that, although originally identified as stress-response mediator, contributes to establishing stem cell differentiation fates. p38α is central for induction of the differentiation fate of the skeletal muscle stem cells (satellite cells) through not fully characterized mechanisms. METHODS: To investigate the global gene transcription program regulated by p38α during satellite cell differentiation (myogenesis), and to specifically address whether this regulation occurs through direct action of p38α on gene promoters, we performed a combination of microarray gene expression and genome-wide binding analyses...
March 15, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27905489/the-mammalian-linc-complex-regulates-genome-transcriptional-responses-to-substrate-rigidity
#12
Samer G Alam, Qiao Zhang, Nripesh Prasad, Yuan Li, Srikar Chamala, Ram Kuchibhotla, Birendra Kc, Varun Aggarwal, Shristi Shrestha, Angela L Jones, Shawn E Levy, Kyle J Roux, Jeffrey A Nickerson, Tanmay P Lele
Mechanical integration of the nucleus with the extracellular matrix (ECM) is established by linkage between the cytoskeleton and the nucleus. This integration is hypothesized to mediate sensing of ECM rigidity, but parsing the function of nucleus-cytoskeleton linkage from other mechanisms has remained a central challenge. Here we took advantage of the fact that the LINC (linker of nucleoskeleton and cytoskeleton) complex is a known molecular linker of the nucleus to the cytoskeleton, and asked how it regulates the sensitivity of genome-wide transcription to substratum rigidity...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905394/uvr2-ensures-transgenerational-genome-stability-under-simulated-natural-uv-b-in-arabidopsis-thaliana
#13
Eva-Maria Willing, Thomas Piofczyk, Andreas Albert, J Barbro Winkler, Korbinian Schneeberger, Ales Pecinka
Ground levels of solar UV-B radiation induce DNA damage. Sessile phototrophic organisms such as vascular plants are recurrently exposed to sunlight and require UV-B photoreception, flavonols shielding, direct reversal of pyrimidine dimers and nucleotide excision repair for resistance against UV-B radiation. However, the frequency of UV-B-induced mutations is unknown in plants. Here we quantify the amount and types of mutations in the offspring of Arabidopsis thaliana wild-type and UV-B-hypersensitive mutants exposed to simulated natural UV-B over their entire life cycle...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27902435/overexpression-of-the-fratricide-immunity-protein-comm-leads-to-growth-inhibition-and-morphological-abnormalities-in-streptococcus-pneumoniae
#14
Daniel Straume, Gro Anita Stamsås, Zhian Salehian, Leiv Sigve Håvarstein
The important human pathogen Streptococcus pneumoniae is a naturally transformable species. When developing the competent state, it expresses proteins involved in DNA-uptake, DNA-processing and homologous recombination. In addition to the proteins required for the transformation process, competent pneumococci express proteins involved in a predatory DNA-acquisition-mechanism termed fratricide. This is a mechanism by which the competent pneumococci secrete a muralytic fratricin termed CbpD, which lyse susceptible sister cells or closely related streptococcal species...
November 28, 2016: Microbiology
https://www.readbyqxmd.com/read/27901072/characterisation-of-functional-domains-in-fission-yeast-ams2-that-are-required-for-core-histone-gene-transcription
#15
Yuko Takayama, Masaki Shirai, Fumie Masuda
Histone gene expression is regulated in a cell cycle-dependent manner, with a peak at S phase, which is crucial for cell division and genome integrity. However, the detailed mechanisms by which expression of histone genes are tightly regulated remain largely unknown. Fission yeast Ams2, a GATA-type zinc finger motif-containing factor, is required for activation of S phase-specific core histone gene transcription. Here we report the molecular characterisation of Ams2. We show that the zinc finger motif in Ams2 is necessary to bind the histone gene promoter region and to activate histone gene transcription...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27901069/molecular-profiling-of-circulating-tumour-cells-identifies-notch1-as-a-principal-regulator-in-advanced-non-small-cell-lung-cancer
#16
Javier Mariscal, Marta Alonso-Nocelo, Laura Muinelo-Romay, Jorge Barbazan, Maria Vieito, Alicia Abalo, Antonio Gomez-Tato, Casares de Cal Maria de Los Angeles, Tomas Garcia-Caballero, Carmela Rodriguez, Elena Brozos, Francisco Baron, Rafael Lopez-Lopez, Miguel Abal
Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27900687/cloning-and-expression-of-metagenomic-dna-in-streptomyces-lividans-and-subsequent-fermentation-for-optimized-production
#17
Yuriy Rebets, Jan Kormanec, Andriy Lutzhetskyy, Kristel Bernaerts, Jozef Anné
The choice of an expression system for the metagenomic DNA of interest is of vital importance for the detection of any particular gene or gene cluster. Most of the screens to date have used the gram-negative bacterium Escherichia coli as a host for metagenomic gene libraries. However, the use of E. coli introduces a potential host bias since only 40 % of the enzymatic activities may be readily recovered by random cloning in E. coli. To recover some of the remaining 60 %, alternative cloning hosts such as Streptomyces spp...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27900363/integration-of-genomics-and-histology-revises-diagnosis-and-enables-effective-therapy-of-refractory-cancer-of-unknown-primary-with-pdl1-amplification
#18
Stefan Gröschel, Martin Bommer, Barbara Hutter, Jan Budczies, David Bonekamp, Christoph Heining, Peter Horak, Martina Fröhlich, Sebastian Uhrig, Daniel Hübschmann, Christina Geörg, Daniela Richter, Nicole Pfarr, Katrin Pfütze, Stephan Wolf, Peter Schirmacher, Dirk Jäger, Christof von Kalle, Benedikt Brors, Hanno Glimm, Wilko Weichert, Albrecht Stenzinger, Stefan Fröhling
Identification of the tissue of origin in cancer of unknown primary (CUP) poses a diagnostic challenge and is critical for directing site-specific therapy. Currently, clinical decision-making in patients with CUP primarily relies on histopathology and clinical features. Comprehensive molecular profiling has the potential to contribute to diagnostic categorization and, most importantly, guide CUP therapy through identification of actionable lesions. We here report the case of an advanced-stage malignancy initially mimicking poorly differentiated soft-tissue sarcoma that did not respond to multiagent chemotherapy...
November 2016: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/27899677/the-mouse-gene-expression-database-gxd-2017-update
#19
Jacqueline H Finger, Constance M Smith, Terry F Hayamizu, Ingeborg J McCright, Jingxia Xu, Meiyee Law, David R Shaw, Richard M Baldarelli, Jon S Beal, Olin Blodgett, Jeff W Campbell, Lori E Corbani, Jill R Lewis, Kim L Forthofer, Pete J Frost, Sharon C Giannatto, Lucie N Hutchins, Dave B Miers, Howie Motenko, Kevin R Stone, Janan T Eppig, James A Kadin, Joel E Richardson, Martin Ringwald
The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. Through curation of the scientific literature and by collaborations with large-scale expression projects, GXD collects and integrates data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. Expression data from both wild-type and mutant mice are included. The expression data are combined with genetic and phenotypic data in Mouse Genome Informatics (MGI) and made readily accessible to many types of database searches...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899664/integration-defective-lentiviral-vector-mediates-efficient-gene-editing-through-homology-directed-repair-in-human-embryonic-stem-cells
#20
Yebo Wang, Yingjia Wang, Tammy Chang, He Huang, Jiing-Kuan Yee
Human embryonic stem cells (hESCs) are used as platforms for disease study, drug screening and cell-based therapy. To facilitate these applications, it is frequently necessary to genetically manipulate the hESC genome. Gene editing with engineered nucleases enables site-specific genetic modification of the human genome through homology-directed repair (HDR). However, the frequency of HDR remains low in hESCs. We combined efficient expression of engineered nucleases and integration-defective lentiviral vector (IDLV) transduction for donor template delivery to mediate HDR in hESC line WA09...
November 28, 2016: Nucleic Acids Research
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