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https://www.readbyqxmd.com/read/28223824/mir182-activates-the-ras-mek-erk-pathway-in-human-oral-cavity-squamous-cell-carcinoma-by-suppressing-rasa1-and-spred1
#1
Jinhui Wang, Wei Wang, Jichen Li, Liji Wu, Mei Song, Qinggang Meng
PURPOSE: The constitutive activation of the Ras-MEK-ERK signaling pathway in oral cavity squamous cell carcinoma (OSCC) has been found to be tightly controlled at multiple levels under physiological conditions. RASA1 and SPRED1 are two important negative regulators of this pathway, but the exact regulating mechanism remains unclear. In this study, we aimed to explore the potential regulating mechanisms involved in the Ras-MEK-ERK signaling pathway in OSCC. MATERIALS AND METHODS: MicroRNA (miRNA) expression was detected by quantitative reverse-transcription polymerase chain reaction...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28223461/identification-of-a-pseudomonas-aeruginosa-pao1-dna-methyltransferase-its-targets-and-physiological-roles
#2
Sebastian Doberenz, Denitsa Eckweiler, Olga Reichert, Vanessa Jensen, Boyke Bunk, Cathrin Spröer, Adrian Kordes, Emanuela Frangipani, Khai Luong, Jonas Korlach, Stephan Heeb, Jörg Overmann, Volkhard Kaever, Susanne Häussler
DNA methylation is widespread among prokaryotes, and most DNA methylation reactions are catalyzed by adenine DNA methyltransferases, which are part of restriction-modification (R-M) systems. R-M systems are known for their role in the defense against foreign DNA; however, DNA methyltransferases also play functional roles in gene regulation. In this study, we used single-molecule real-time (SMRT) sequencing to uncover the genome-wide DNA methylation pattern in the opportunistic pathogen Pseudomonas aeruginosa PAO1...
February 21, 2017: MBio
https://www.readbyqxmd.com/read/28221375/circadian-deep-sequencing-reveals-stress-response-genes-that-adopt-robust-rhythmic-expression-during-aging
#3
Rachael C Kuintzle, Eileen S Chow, Tara N Westby, Barbara O Gvakharia, Jadwiga M Giebultowicz, David A Hendrix
Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions...
February 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28214735/rna-based-control-mechanisms-of-clostridium-difficile
#4
REVIEW
Olga Soutourina
Clostridium difficile (CD)-associated diarrhoea is currently the most prevalent nosocomial diarrhoea worldwide. Many characteristics of CD pathogenicity remain poorly understood. Recent data strongly indicate the importance of an RNA network for the control of gene expression in CD. More than 200 regulatory RNAs have been identified by deep sequencing and targeted approaches, including Hfq-dependent trans riboregulators, cis-antisense RNAs, CRISPR RNAs, and c-di-GMP-responsive riboswitches. These regulatory RNAs are involved in the control of major processes in the CD infection cycle, for example motility, biofilm formation, adhesion, sporulation, stress response, and defence against bacteriophages...
February 16, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28214361/identification-of-arabidopsis-genic-and-non-genic-promoters-by-paired-end-sequencing-of-tss-tags
#5
Mutsutomo Tokizawa, Kazutaka Kusunoki, Hiroyuki Koyama, Atsushi Kurotani, Tetsuya Sakurai, Yutaka Suzuki, Tomoaki Sakamoto, Tetsuya Kurata, Yoshiharu Y Yamamoto
Information about transcription start sites (TSSs) provides foundational data for analyses of promoter architecture. In this report, we used paired- and single-end deep sequencing to analyze Arabidopsis TSS tags from several libraries prepared from roots, shoots, flowers, and etiolated seedlings. The clustering of approximately 33 million mapped TSS tags led to the identification of 324,461 promoters that covered 79.7% (21,672/27,206) of protein-coding genes in the Arabidopsis genome. In addition, we identified intragenic, antisense, and Orphan promoters that were not associated with any gene models...
February 18, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28209997/antisense-mir-132-blockade-via-the-ache-r-splice-variant-mitigates-cortical-inflammation
#6
Nibha Mishra, Lyndon Friedson, Geula Hanin, Uriya Bekenstein, Meshi Volovich, Estelle R Bennett, David S Greenberg, Hermona Soreq
MicroRNA (miR)-132 brain-to-body messages suppress inflammation by targeting acetylcholinesterase (AChE), but the target specificity of 3'-AChE splice variants and the signaling pathways involved remain unknown. Using surface plasmon resonance (SPR), we identified preferential miR-132 targeting of soluble AChE-R over synaptic-bound AChE-S, potentiating miR-132-mediated brain and body cholinergic suppression of pro-inflammatory cytokines. Inversely, bacterial lipopolysaccharide (LPS) reduced multiple miR-132 targets, suppressed AChE-S more than AChE-R and elevated inflammatory hallmarks...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209220/very-low-density-lipoprotein-associated-apolipoproteins-predict-cardiovascular-events-and-are-lowered-by-inhibition%C3%A2-of%C3%A2-apoc-iii
#7
Raimund Pechlaner, Sotirios Tsimikas, Xiaoke Yin, Peter Willeit, Ferheen Baig, Peter Santer, Friedrich Oberhollenzer, Georg Egger, Joseph L Witztum, Veronica J Alexander, Johann Willeit, Stefan Kiechl, Manuel Mayr
BACKGROUND: Routine apolipoprotein (apo) measurements for cardiovascular disease (CVD) are restricted to apoA-I and apoB. Here, the authors measured an unprecedented range of apolipoproteins in a prospective, population-based study and relate their plasma levels to risk of CVD. OBJECTIVES: This study sought to measure apolipoproteins directly by mass spectrometry and compare their associations with incident CVD and to obtain a system-level understanding of the correlations of apolipoproteins with the plasma lipidome and proteome...
February 21, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28208626/2-o-methyl-rna-ethylene-bridged-nucleic-acid-chimera-antisense-oligonucleotides-to-induce-dystrophin-exon-45-skipping
#8
REVIEW
Tomoko Lee, Hiroyuki Awano, Mariko Yagi, Masaaki Matsumoto, Nobuaki Watanabe, Ryoya Goda, Makoto Koizumi, Yasuhiro Takeshima, Masafumi Matsuo
Duchenne muscular dystrophy (DMD) is a fatal muscle-wasting disease characterized by dystrophin deficiency from mutations in the dystrophin gene. Antisense oligonucleotide (AO)-mediated exon skipping targets restoration of the dystrophin reading frame to allow production of an internally deleted dystrophin protein with functional benefit for DMD patients who have out-of-frame deletions. After accelerated US approval of eteplirsen (Exondys 51), which targets dystrophin exon 51 for skipping, efforts are now focused on targeting other exons...
February 10, 2017: Genes
https://www.readbyqxmd.com/read/28208060/rna-toxicity-and-foci-formation-in-microsatellite-expansion-diseases
#9
REVIEW
Nan Zhang, Tetsuo Ashizawa
More than 30 incurable neurological and neuromuscular diseases are caused by simple microsatellite expansions consisted of 3-6 nucleotides. These repeats can occur in non-coding regions and often result in a dominantly inherited disease phenotype that is characteristic of a toxic RNA gain-of-function. The expanded RNA adopts unusual secondary structures, sequesters various RNA binding proteins to form insoluble nuclear foci, and causes cellular defects at a multisystem level. Nuclear foci are dynamic in size, shape and colocalization of RNA binding proteins in different expansion diseases and tissue types...
February 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28196650/protective-role-of-p53-in-acetaminophen-hepatotoxicity
#10
Yazhen Huo, Shutao Yin, Mingzhu Yan, Sanda Win, Tin Aung Than, Mariam Aghajan, Hongbo Hu, Neil Kaplowitz
p53 is a tumor suppressor with a pro-death role in many conditions. However, in some contexts, evidence supports a pro-survival function. p53 has been shown to be activated in acetaminophen (APAP) toxicity but the impact of this on toxicity is uncertain. In the present study, we have found that p53 plays a protective role in APAP-induced liver injury. We inhibited p53 using three different approaches in mice, pifithrin-α (PFTα), knockdown of p53 expression with antisense oligonucleotide, and p53 knockout...
February 11, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28193854/gene-activation-of-smn-by-selective-disruption-of-lncrna-mediated-recruitment-of-prc2-for-the-treatment-of-spinal-muscular-atrophy
#11
Caroline J Woo, Verena K Maier, Roshni Davey, James Brennan, Guangde Li, John Brothers, Brian Schwartz, Susana Gordo, Anne Kasper, Trevor R Okamoto, Hans E Johansson, Berhan Mandefro, Dhruv Sareen, Peter Bialek, B Nelson Chau, Balkrishen Bhat, David Bullough, James Barsoum
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by progressive motor neuron loss and caused by mutations in SMN1 (Survival Motor Neuron 1). The disease severity inversely correlates with the copy number of SMN2, a duplicated gene that is nearly identical to SMN1. We have delineated a mechanism of transcriptional regulation in the SMN2 locus. A previously uncharacterized long noncoding RNA (lncRNA), SMN-antisense 1 (SMN-AS1), represses SMN2 expression by recruiting the Polycomb Repressive Complex 2 (PRC2) to its locus...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193768/exploiting-the-p53-pathway-for-therapy
#12
Chit Fang Cheok, David Philip Lane
The excitement around the entry into the clinic of the first generation of p53-specific drugs has become muted as the hoped-for dramatic clinical responses have not yet been seen. However, these pioneer molecules have become exceptionally powerful tools in the analysis of the p53 pathway and, as a result, a whole spectrum of new interventions are being explored. These include entirely novel and innovative approaches to drug discovery, such as the use of exon-skipping antisense oligonucleotides and T-cell-receptor-based molecules...
February 13, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28192937/amplification-and-quantification-of-an-antisense-oligonucleotide-from-target-microrna-using-programmable-dna-and-a-biological-nanopore
#13
Moe Hiratani, Masayuki Ohara, Ryuji Kawano
This paper describes a strategy for autonomous diagnoses of cancers using microRNA (miRNA) and therapy for tumor cells by DNA computing techniques and nanopore measurement. Theranostics, which involves the combination of diagnosis and therapy, has emerged as an approach for personalized medicine or point-of-care cancer diagnostics. DNA computing will become a potent tool for theranostics because it functions completely autonomously without the need for external regulations. However, conventional theranostics using DNA computing involves a one-to-one reaction in which a single input molecule generates a single output molecule; the concentration of the antisense drug is insufficient for the therapy in this type of reaction...
February 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28192799/cyp1b1-regulates-ocular-fissure-closure-through-a-retinoic-acid-independent-pathway
#14
Antionette L Williams, Jessica Eason, Bahaar Chawla, Brenda L Bohnsack
Purpose: Mutations in the CYP1B1 gene are the most commonly identified genetic causes of primary infantile-onset glaucoma. Despite this disease association, the role of CYP1B1 in eye development and its in vivo substrate remain unknown. In the present study, we used zebrafish to elucidate the mechanism by which cyp1b1 regulates eye development. Methods: Zebrafish eye and neural crest development were analyzed using live imaging of transgenic zebrafish embryos, in situ hybridization, immunostaining, TUNEL assay, and methylacrylate sections...
February 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28192479/comparison-of-zebrafish-tmem88a-mutant-and-morpholino-knockdown-phenotypes
#15
Alexander M J Eve, Elsie S Place, James C Smith
Tmem88a is a transmembrane protein that is thought to be a negative regulator of the Wnt signalling pathway. Several groups have used antisense morpholino oligonucleotides in an effort to characterise the role of tmem88a in zebrafish cardiovascular development, but they have not obtained consistent results. Here, we generate an 8 bp deletion in the coding region of the tmem88a locus using TALENs, and we have gone on to establish a viable homozygous tmem88aΔ8 mutant line. Although tmem88aΔ8 mutants have reduced expression of some key haematopoietic genes, differentiation of erythrocytes and neutrophils is unaffected, contradicting our previous study using antisense morpholino oligonucleotides...
2017: PloS One
https://www.readbyqxmd.com/read/28192393/nusinersen-an-antisense-oligonucleotide-drug-for-spinal-muscular-atrophy
#16
David R Corey
No abstract text is available yet for this article.
February 13, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28192196/quantification-of-various-app-mrna-isoforms-and-epistasis-in-lesch-nyhan-disease
#17
Khue Vu Nguyen, William L Nyhan
The present work is the development of a simple and specific kinetic method based on RT-PCR technique coupled with direct sequencing for quantification of various amyloid precursor protein-mRNA isoforms (APP-mRNA isoforms) in biological samples, especially for identifying the most abundant one that may decisive for the normal status or disease risk. Application of this kinetic method to the Lesch-Nyhan disease (LND) was performed and results indicated an epistasis between mutated hypoxanthine phosphoribosyltransferase1 (HPRT1) and APP genes...
February 10, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188287/a-to-i-rna-editing-up-regulates-human-dihydrofolate-reductase-in-breast-cancer
#18
Masataka Nakano, Tatsuki Fukami, Saki Gotoh, Miki Nakajima
Dihydrofolate reductase (DHFR) plays a key role in folate metabolism and is a target molecule of methotrexate. An increase in the cellular expression level of DHFR is one of the mechanisms of tumor resistance to methotrexate. The present study investigated the possibility that adenosine-to-inosine RNA editing, which causes nucleotide conversion by adenosine deaminase acting on RNA (ADAR) enzymes, might modulate DHFR expression. In human breast adenocarcinoma-derived MCF-7 cells, 26 RNA editing sites were identified in the 3'-UTR of DHFR...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28188264/immortalized-human-myotonic-dystrophy-muscle-cell-lines-to-assess-therapeutic-compounds
#19
Arandel Ludovic, Polay-Espinosa Micaela, Matloka Magdalena, Bazinet Audrey, De Dea Diniz Damily, Naouar Naïra, Rau Frédérique, Jollet Arnaud, Edom-Vovard Frédérique, Mamchaoui Kamel, Tarnopolsky Mark, Puymirat Jack, Battail Christophe, Boland Anne, Deleuze Jean-Francois, Mouly Vincent, Klein F Arnaud, Furling Denis
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA-aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared to control and DM2 cells...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28187742/regulatory-role-of-cytosolic-phospholipase-a2-alpha-in-the-induction-of-cd40-in-microglia
#20
Yafa Fetfet Malada-Edelstein, Nurit Hadad, Rachel Levy
BACKGROUND: The aberrant expression of CD40, a co-stimulatory receptor found on the antigen-presenting cells, is involved in the pathogenesis of various degenerative diseases. Our previous study demonstrated that the reduction of cytosolic phospholipase A2 alpha (cPLA2α) protein overexpression and activation in the spinal cord of a mouse model of ALS, hmSOD1 G93A, inhibited CD40 upregulation in microglia. The present study was designed to determine whether cPLA2α has a direct, participatory role in the molecular events leading to CD40 induction...
February 10, 2017: Journal of Neuroinflammation
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