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Expression genomic integration

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https://www.readbyqxmd.com/read/28225754/targeting-a-car-to-the-trac-locus-with-crispr-cas9-enhances-tumour-rejection
#1
Justin Eyquem, Jorge Mansilla-Soto, Theodoros Giavridis, Sjoukje J C van der Stegen, Mohamad Hamieh, Kristen M Cunanan, Ashlesha Odak, Mithat Gönen, Michel Sadelain
Chimeric antigen receptors (CARs) are synthetic receptors that redirect and reprogram T cells to mediate tumour rejection. The most successful CARs used to date are those targeting CD19 (ref. 2), which offer the prospect of complete remission in patients with chemorefractory or relapsed B-cell malignancies. CARs are typically transduced into the T cells of a patient using γ-retroviral vectors or other randomly integrating vectors, which may result in clonal expansion, oncogenic transformation, variegated transgene expression and transcriptional silencing...
February 22, 2017: Nature
https://www.readbyqxmd.com/read/28222698/atgc-transcriptomics-a-web-based-application-to-integrate-explore-and-analyze-de-novo-transcriptomic-data
#2
Sergio Gonzalez, Bernardo Clavijo, Máximo Rivarola, Patricio Moreno, Paula Fernandez, Joaquín Dopazo, Norma Paniego
BACKGROUND: In the last years, applications based on massively parallelized RNA sequencing (RNA-seq) have become valuable approaches for studying non-model species, e.g., without a fully sequenced genome. RNA-seq is a useful tool for detecting novel transcripts and genetic variations and for evaluating differential gene expression by digital measurements. The large and complex datasets resulting from functional genomic experiments represent a challenge in data processing, management, and analysis...
February 22, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28221768/formation-of-nitrogenase-nifdk-tetramers-in-the-mitochondria-of-saccharomyces-cerevisiae
#3
Stefan Burén, Eric M Young, Elizabeth A Sweeny, Gema López-Torrejón, Marcel Veldhuizen, Christopher A Voigt, Luis M Rubio
Transferring the prokaryotic enzyme nitrogenase into a eukaryotic host with the final aim of developing N2 fixing cereal crops would revolutionize agricultural systems worldwide. Targeting it to mitochondria has potential advantages because of the organelle's high O2 consumption and the presence of bacterial-type iron-sulfur cluster biosynthetic machinery. In this study, we constructed 96 strains of Saccharomyces cerevisiae where transcriptional units comprising nine Azotobacter vinelandii nif genes (nifHDKUSMBEN) were integrated into the genome...
February 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28220024/molecular-subtypes-improve-prognostic-value-of-international-metastatic-renal-cell-carcinoma-database-consortium-prognostic-model
#4
Guillermo de Velasco, Aedín C Culhane, André P Fay, A Ari Hakimi, Martin H Voss, Nizar M Tannir, Pheroze Tamboli, Leonard J Appleman, Joaquim Bellmunt, W Kimryn Rathmell, Laurence Albiges, James J Hsieh, Daniel Y C Heng, Sabina Signoretti, Toni K Choueiri
INTRODUCTION: Gene-expression signatures for prognosis have been reported in localized renal cell carcinoma (RCC). The aim of this study was to test the predictive power of two different signatures, ClearCode34, a 34-gene signature model [Eur Urol 2014;66:77-84], and an 8-gene signature model [Eur Urol 2015;67:17-20], in the setting of systemic therapy for metastatic disease. MATERIALS AND METHODS: Metastatic RCC (mRCC) patients from five institutions who were part of TCGA were identified and clinical data were retrieved...
February 20, 2017: Oncologist
https://www.readbyqxmd.com/read/28219948/genomic-integration-of-wnt-%C3%AE-catenin-and-bmp-smad1-signaling-coordinates-foregut-and-hindgut-transcriptional-program
#5
Mariana L Stevens, Praneet Chaturvedi, Scott A Rankin, Melissa Macdonald, Sajjeev Jagannathan, Masashi Yukawa, Artem Barski, Aaron M Zorn
Digestive system development is orchestrated by combinatorial signaling interactions between endoderm and mesoderm, but how these signals are integrated in the genome is poorly understood. Here we identified the transcriptomes of Xenopus foregut and hindgut progenitors, which are conserved with mammals. Using RNA-seq and ChIP-seq we show that BMP/Smad1 regulates dorsal-ventral gene expression in both the endoderm and mesoderm, whereas Wnt/β-catenin acts as a genome-wide toggle between foregut and hindgut programs...
February 20, 2017: Development
https://www.readbyqxmd.com/read/28218261/pneumococcal-prophages-are-diverse-but-not-without-structure-or-history
#6
Angela B Brueggemann, Caroline L Harrold, Reza Rezaei Javan, Andries J van Tonder, Angus J McDonnell, Ben A Edwards
Bacteriophages (phages) infect many bacterial species, but little is known about the diversity of phages among the pneumococcus, a leading global pathogen. The objectives of this study were to determine the prevalence, diversity and molecular epidemiology of prophages (phage DNA integrated within the bacterial genome) among pneumococci isolated over the past 90 years. Nearly 500 pneumococcal genomes were investigated and RNA sequencing was used to explore prophage gene expression. We revealed that every pneumococcal genome contained prophage DNA...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217746/integrated-regulatory-and-metabolic-networks-of-the-marine-diatom-phaeodactylum-tricornutum-predict-the-response-to-rising-co2-levels
#7
Jennifer Levering, Christopher L Dupont, Andrew E Allen, Bernhard O Palsson, Karsten Zengler
Diatoms are eukaryotic microalgae that are responsible for up to 40% of the ocean's primary productivity. How diatoms respond to environmental perturbations such as elevated carbon concentrations in the atmosphere is currently poorly understood. We developed a transcriptional regulatory network based on various transcriptome sequencing expression libraries for different environmental responses to gain insight into the marine diatom's metabolic and regulatory interactions and provide a comprehensive framework of responses to increasing atmospheric carbon levels...
January 2017: MSystems
https://www.readbyqxmd.com/read/28217257/regulation-of-hepatic-microrna-expression-by-hepatocyte-nuclear-factor-4-alpha
#8
Hong Lu, Xiaohong Lei, Jerry Liu, Curtis Klaassen
AIM: To uncover the role of hepatocyte nuclear factor 4 alpha (HNF4α) in regulating hepatic expression of microRNAs. METHODS: Microarray and real-time PCR were used to determine hepatic expression of microRNAs in young-adult mice lacking Hnf4α expression in liver (Hnf4α-LivKO). Integrative genomics viewer software was used to analyze the public chromatin immunoprecipitation-sequencing datasets for DNA-binding of HNF4α, RNA polymerase-II, and histone modifications to loci of microRNAs in mouse liver and human hepatoma cells...
February 8, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#9
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213501/immature-lymphocytes-inhibit-rag1-and-rag2-transcription-and-v-d-j-recombination-in-response-to-dna-double-strand-breaks
#10
Megan R Fisher, Adrian Rivera-Reyes, Noah B Bloch, David G Schatz, Craig H Bassing
Mammalian cells have evolved a common DNA damage response (DDR) that sustains cellular function, maintains genomic integrity, and suppresses malignant transformation. In pre-B cells, DNA double-strand breaks (DSBs) induced at Igκ loci by the Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes. We previously reported that RAG DSBs induced at one Igκ allele signal through the ataxia telangiectasia mutated (ATM) kinase to feedback-inhibit RAG expression and RAG cleavage of the other Igκ allele...
February 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#11
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212550/plcb4-copy-gain-and-plc%C3%A3-4-overexpression-in-primary-gastrointestinal-stromal-tumors-integrative-characterization-of-a-lipid-catabolizing-enzyme-associated-with-worse-disease-free-survival
#12
Chien-Feng Li, Ting-Ting Liu, I-Chieh Chuang, Yen-Yang Chen, Fu-Min Fang, Ti-Chun Chan, Wan-Shan Li, Hsuan-Ying Huang
To explore the implications of lipid catabolism-associated genes in gastrointestinal stromal tumors, we reappraised transcriptomic and genomic datasets and identified copy-gained and differentially upregulated PLCB4 gene associated with tumor progression. On full sections, PLCB4 mRNA abundance and PLCß4 immunoexpression were validated in 70 cases. On tissue microarrays, PLCB4 gene copies and PLCß4 immunoexpression were both informative in 350 cases with KIT/PDGFRA/BRAF genotypes noted in 213. In GIST48 cell line, we stably silenced PLCB4 and YAP1 to characterize their functional effects and regulatory link...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212413/scarless-deletion-of-up-to-seven-methyl-accepting-chemotaxis-genes-with-an-optimized-method-highlights-key-function-of-chem-in-salmonella-typhimurium
#13
Stefanie Hoffmann, Christiane Schmidt, Steffi Walter, Jennifer K Bender, Roman G Gerlach
Site-directed scarless mutagenesis is an essential tool of modern pathogenesis research. We describe an optimized two-step protocol for genome editing in Salmonella enterica serovar Typhimurium to enable multiple sequential mutagenesis steps in a single strain. The system is based on the λ Red recombinase-catalyzed integration of a selectable antibiotics resistance marker followed by replacement of this cassette. Markerless mutants are selected by expressing the meganuclease I-SceI which induces double-strand breaks in bacteria still harboring the resistance locus...
2017: PloS One
https://www.readbyqxmd.com/read/28212312/genome-wide-prediction-of-dna-methylation-using-dna-composition-and-sequence-complexity-in-human
#14
Chengchao Wu, Shixin Yao, Xinghao Li, Chujia Chen, Xuehai Hu
DNA methylation plays a significant role in transcriptional regulation by repressing activity. Change of the DNA methylation level is an important factor affecting the expression of target genes and downstream phenotypes. Because current experimental technologies can only assay a small proportion of CpG sites in the human genome, it is urgent to develop reliable computational models for predicting genome-wide DNA methylation. Here, we proposed a novel algorithm that accurately extracted sequence complexity features (seven features) and developed a support-vector-machine-based prediction model with integration of the reported DNA composition features (trinucleotide frequency and GC content, 65 features) by utilizing the methylation profiles of embryonic stem cells in human...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28212305/epigenetic-landscape-during-coronavirus-infection
#15
Alexandra Schäfer, Ralph S Baric
Coronaviruses (CoV) comprise a large group of emerging human and animal pathogens, including the highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) strains. The molecular mechanisms regulating emerging coronavirus pathogenesis are complex and include virus-host interactions associated with entry, replication, egress and innate immune control. Epigenetics research investigates the genetic and non-genetic factors that regulate phenotypic variation, usually caused by external and environmental factors that alter host expression patterns and performance without any change in the underlying genotype...
February 15, 2017: Pathogens
https://www.readbyqxmd.com/read/28209772/maternal-smoke-exposure-decreases-mesenchymal-proliferation-and-modulates-rho-gtpase-dependent-actin-cytoskeletal-signaling-in-fetal-lungs
#16
Uchenna Unachukwu, Jordis Trischler, Monica Goldklang, Rui Xiao, Jeanine D'Armiento
The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m(3)) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28209199/making-life-difficult-for-clostridium-difficile-augmenting-the-pathogen-s-metabolic-model-with-transcriptomic-and-codon-usage-data-for-better-therapeutic-target-characterization
#17
Sara Saheb Kashaf, Claudio Angione, Pietro Lió
BACKGROUND: Clostridium difficile is a bacterium which can infect various animal species, including humans. Infection with this bacterium is a leading healthcare-associated illness. A better understanding of this organism and the relationship between its genotype and phenotype is essential to the search for an effective treatment. Genome-scale metabolic models contain all known biochemical reactions of a microorganism and can be used to investigate this relationship. RESULTS: We present icdf834, an updated metabolic network of C...
February 16, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28209150/penicillin-production-in-industrial-strain-penicillium-chrysogenum-p2niad18-is-not-dependent-on-the-copy-number-of-biosynthesis-genes
#18
Sandra Ziemons, Katerina Koutsantas, Kordula Becker, Tim Dahlmann, Ulrich Kück
BACKGROUND: Multi-copy gene integration into microbial genomes is a conventional tool for obtaining improved gene expression. For Penicillium chrysogenum, the fungal producer of the beta-lactam antibiotic penicillin, many production strains carry multiple copies of the penicillin biosynthesis gene cluster. This discovery led to the generally accepted view that high penicillin titers are the result of multiple copies of penicillin genes. Here we investigated strain P2niaD18, a production line that carries only two copies of the penicillin gene cluster...
February 16, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/28206814/biomarkers-in-tumor-microenvironment-upregulation-of-fibroblast-activation-protein-%C3%AE-correlates-with-gastric-cancer-progression-and-poor-prognosis
#19
Mengmou Hu, Chengjia Qian, Ziwei Hu, Bojian Fei, Haibo Zhou
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recent evidence points to importance of cross talk between cancer cells and the surrounding stroma on gastric cancer progression. Tumor microenvironment biomarkers thus represent a new opportunity for diagnostics innovation. Reactive stromal fibroblasts selectively express the fibroblast activation protein alpha (FAP-α), a homodimeric integral membrane gelatinase that belongs to the serine protease family. We report here that FAP-α expression is significantly elevated in gastric cancer samples by more than fivefold (p < 0...
January 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28205537/her2-alterations-in-muscle-invasive-bladder-cancer-patient-selection-beyond-protein-expression-for-targeted-therapy
#20
Bernhard Kiss, Alexander W Wyatt, James Douglas, Veronika Skuginna, Fan Mo, Shawn Anderson, Diana Rotzer, Achim Fleischmann, Vera Genitsch, Tetsutaro Hayashi, Maja Neuenschwander, Christine Buerki, Elai Davicioni, Colin Collins, George N Thalmann, Peter C Black, Roland Seiler
Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC...
February 16, 2017: Scientific Reports
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