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https://www.readbyqxmd.com/read/28335559/the-optimization-and-characterization-of-an-rna-cleaving-fluorogenic-dnazyme-probe-for-mda-mb-231-cell-detection
#1
Pengcheng Xue, Shengnan He, Yu Mao, Long Qu, Feng Liu, Chunyan Tan, Yuyang Jiang, Ying Tan
Breast cancer is one of the most frequently diagnosed cancers in females worldwide and lacks specific biomarkers for early detection. In a previous study, we obtained a selective RNA-cleaving Fluorogenic DNAzyme (RFD) probe against MDA-MB-231 cells, typical breast cancer cells, through the systematic evolution of ligands by exponential process (SELEX). To improve the performance of this probe for actual application, we carried out a series of optimization experiments on the pH value of a reaction buffer, the type and concentration of cofactor ions, and sequence minimization...
March 21, 2017: Sensors
https://www.readbyqxmd.com/read/28335314/effects-of-g-quadruplex-topology-on-electronic-transfer-integrals
#2
Wenming Sun, Daniele Varsano, Rosa Di Felice
G-quadruplex is a quadruple helical form of nucleic acids that can appear in guanine-rich parts of the genome. The basic unit is the G-tetrad, a planar assembly of four guanines connected by eight hydrogen bonds. Its rich topology and its possible relevance as a drug target for a number of diseases have stimulated several structural studies. The superior stiffness and electronic π-π overlap between consecutive G-tetrads suggest exploitation for nanotechnologies. Here we inspect the intimate link between the structure and the electronic properties, with focus on charge transfer parameters...
October 15, 2016: Nanomaterials
https://www.readbyqxmd.com/read/28335037/lrsam1-mediated-ubiquitylation-is-disrupted-in-axonal-charcot-marie-tooth-disease-2p
#3
Johanna E Hakonen, Vincenzo Sorrentino, Rossella Avagliano Trezza, Marit B de Wissel, Marlene van den Berg, Boris Bleijlevens, Fred van Ruissen, Ben Distel, Frank Baas, Noam Zelcer, Marian A J Weterman
Charcot-Marie-Tooth (CMT) disease type 2 is a genetically heterogeneous group of inherited neuropathies characterized by motor and sensory deficits as a result of peripheral axonal degeneration. We recently reported a frameshift mutation in the RING domain of LRSAM1 (c.2121_2122dup, p.Leu708Argfs) that encodes an E3 ubiquitin ligase, as the cause of axonal type CMT (CMT2P). However, the frequency of LRSAM1 mutations in CMT2 and the functional basis for their association with disease remains unknown. In this study we evaluated LRSAM1 mutations in two large Dutch cohorts...
March 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28335020/znhit3-is-defective-in-peho-syndrome-a-severe-encephalopathy-with-cerebellar-granule-neuron-loss
#4
Anna-Kaisa Anttonen, Anni Laari, Maria Kousi, Yawei J Yang, Tiina Jääskeläinen, Mirja Somer, Eija Siintola, Eveliina Jakkula, Mikko Muona, Saara Tegelberg, Tuula Lönnqvist, Helena Pihko, Leena Valanne, Anders Paetau, Melody P Lun, Johanna Hästbacka, Outi Kopra, Tarja Joensuu, Nicholas Katsanis, Maria K Lehtinen, Jorma J Palvimo, Anna-Elina Lehesjoki
Progressive encephalopathy with oedema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an early childhood onset, severe autosomal recessive encephalopathy characterized by extreme cerebellar atrophy due to almost total granule neuron loss. By combining homozygosity mapping in Finnish families with Sanger sequencing of positional candidate genes and with exome sequencing a homozygous missense substitution of leucine for serine at codon 31 in ZNHIT3 was identified as the primary cause of PEHO syndrome. ZNHIT3 encodes a nuclear zinc finger protein previously implicated in transcriptional regulation and in small nucleolar ribonucleoprotein particle assembly and thus possibly to pre-ribosomal RNA processing...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28334952/dnmt1-mutations-found-in-hsanie-patients-affect-interaction-with-uhrf1-and-neuronal-differentiation
#5
Martha Smets, Stephanie Link, Patricia Wolf, Katrin Schneider, Veronica Solis, Joel Ryan, Daniela Meilinger, Weihua Qin, Heinrich Leonhardt
DNMT1 is recruited to substrate sites by PCNA and UHRF1 to maintain DNA methylation after replication. The cell cycle dependent recruitment of DNMT1 is mediated by the PCNA-binding domain (PBD) and the targeting sequence (TS) within the N-terminal regulatory domain. The TS domain was found to be mutated in patients suffering from hereditary sensory and autonomic neuropathies with dementia and hearing loss (HSANIE) and autosomal dominant cerebellar ataxia deafness and narcolepsy (ADCA-DN) and is associated with global hypomethylation and site specific hypermethylation...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334904/genome-wide-mapping-of-infection-induced-sine-rnas-reveals-a-role-in-selective-mrna-export
#6
John Karijolich, Yang Zhao, Ravi Alla, Britt Glaunsinger
Short interspersed nuclear elements (SINEs) are retrotransposons evolutionarily derived from endogenous RNA Polymerase III RNAs. Though SINE elements have undergone exaptation into gene regulatory elements, how transcribed SINE RNA impacts transcriptional and post-transcriptional regulation is largely unknown. This is partly due to a lack of information regarding which of the loci have transcriptional potential. Here, we present an approach (short interspersed nuclear element sequencing, SINE-seq), which selectively profiles RNA Polymerase III-derived SINE RNA, thereby identifying transcriptionally active SINE loci...
March 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334903/n6-methyladenosine-alters-rna-structure-to-regulate-binding-of-a-low-complexity-protein
#7
Nian Liu, Katherine I Zhou, Marc Parisien, Qing Dai, Luda Diatchenko, Tao Pan
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic messenger RNA (mRNA), and affects almost every stage of the mRNA life cycle. The YTH-domain proteins can specifically recognize m6A modification to control mRNA maturation, translation and decay. m6A can also alter RNA structures to affect RNA-protein interactions in cells. Here, we show that m6A increases the accessibility of its surrounding RNA sequence to bind heterogeneous nuclear ribonucleoprotein G (HNRNPG). Furthermore, HNRNPG binds m6A-methylated RNAs through its C-terminal low-complexity region, which self-assembles into large particles in vitro...
February 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334889/the-primary-transcriptome-of-neisseria-meningitidis-and-its-interaction-with-the-rna-chaperone-hfq
#8
Nadja Heidrich, Saskia Bauriedl, Lars Barquist, Lei Li, Christoph Schoen, Jörg Vogel
Neisseria meningitidis is a human commensal that can also cause life-threatening meningitis and septicemia. Despite growing evidence for RNA-based regulation in meningococci, their transcriptome structure and output of regulatory small RNAs (sRNAs) are incompletely understood. Using dRNA-seq, we have mapped at single-nucleotide resolution the primary transcriptome of N. meningitidis strain 8013. Annotation of 1625 transcriptional start sites defines transcription units for most protein-coding genes but also reveals a paucity of classical σ70-type promoters, suggesting the existence of activators that compensate for the lack of -35 consensus sequences in N...
March 17, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334876/pdgfrb-gain-of-function-mutations-in-sporadic-infantile-myofibromatosis
#9
Florence A Arts, Raf Sciot, Bénédicte Brichard, Marleen Renard, Audrey de Rocca Serra, Guillaume Dachy, Laura A Noël, Amélie I Velghe, Christine Galant, Maria Debiec-Rychter, An Van Damme, Miikka Vikkula, Raphaël Helaers, Nisha Limaye, Hélène A Poirel, Jean-Baptiste Demoulin
Infantile myofibromatosis is one of the most prevalent soft tissue tumors of infancy and childhood. Multifocal nodules with visceral lesions are associated with a poor prognosis. A few familial cases have been linked to mutations in various genes including PDGFRB. In this study, we sequenced PDGFRB, which encodes a receptor tyrosine kinase, in 16 cases of myofibromatosis or solitary myofibroma. Mutations in the coding sequence of PDGFRB were identified in 6 out of 8 patients with the sporadic multicentric form of the disease and in 1 out of 8 patients with isolated myofibroma...
March 3, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334865/structure-of-human-pofut1-its-requirement-in-ligand-independent-oncogenic-notch-signaling-and-functional-effects-of-dowling-degos-mutations
#10
Brian J McMillan, Brandon Zimmerman, Emily D Egan, Michael Lofgren, Xiang Xu, Anthony Hesser, Stephen C Blacklow
Protein O-fucosyltransferase-1 (POFUT1), which transfers fucose residues to acceptor sites on serine and threonine residues of epidermal growth factor-like repeats of recipient proteins, is essential for Notch signal transduction in mammals. Here, we examine the consequences of POFUT1 loss on the oncogenic signaling associated with certain leukemia-associated mutations of human Notch1, report the structures of human POFUT1 in free and GDP-fucose bound states, and assess the effects of Dowling-Degos mutations on human POFUT1 function...
March 17, 2017: Glycobiology
https://www.readbyqxmd.com/read/28334833/chip-seq-analysis-of-the-luxr-type-regulator-vjbr-reveals-novel-insights-into-the-brucella-virulence-gene-expression-network
#11
Claudia L Kleinman, Gabriela Sycz, Hernán R Bonomi, Romina M Rodríguez, Angeles Zorreguieta, Rodrigo Sieira
LuxR-type transcription factors control diverse physiological functions necessary for bacterial adaptation to environmental changes. In the intracellular pathogen Brucella, the LuxR homolog VjbR has been shown to regulate the expression of virulence factors acting at early stages of the intracellular infection and, directly or indirectly, hundreds of additional genes. However, the precise determination of VjbR direct targets has so far proved elusive. Here, we performed chromatin immunoprecipitation of VjbR followed by next-generation sequencing (ChIP-seq)...
March 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334828/flexible-crispr-library-construction-using-parallel-oligonucleotide-retrieval
#12
Abigail Read, Shaojian Gao, Eric Batchelor, Ji Luo
CRISPR/Cas9-based gene knockout libraries have emerged as a powerful tool for functional screens. We present here a set of pre-designed human and mouse sgRNA sequences that are optimized for both high on-target potency and low off-target effect. To maximize the chance of target gene inactivation, sgRNAs were curated to target both 5΄ constitutive exons and exons that encode conserved protein domains. We describe here a robust and cost-effective method to construct multiple small sized CRISPR library from a single oligo pool generated by array synthesis using parallel oligonucleotide retrieval...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334803/statistical-analysis-of-genetic-interactions-in-tn-seq-data
#13
Michael A DeJesus, Subhalaxmi Nambi, Clare M Smith, Richard E Baker, Christopher M Sassetti, Thomas R Ioerger
Tn-Seq is an experimental method for probing the functions of genes through construction of complex random transposon insertion libraries and quantification of each mutant's abundance using next-generation sequencing. An important emerging application of Tn-Seq is for identifying genetic interactions, which involves comparing Tn mutant libraries generated in different genetic backgrounds (e.g. wild-type strain versus knockout strain). Several analytical methods have been proposed for analyzing Tn-Seq data to identify genetic interactions, including estimating relative fitness ratios and fitting a generalized linear model...
February 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334774/high-tolerance-to-self-targeting-of-the-genome-by-the-endogenous-crispr-cas-system-in-an-archaeon
#14
Aris-Edda Stachler, Israela Turgeman-Grott, Ella Shtifman-Segal, Thorsten Allers, Anita Marchfelder, Uri Gophna
CRISPR-Cas systems allow bacteria and archaea to acquire sequence-specific immunity against selfish genetic elements such as viruses and plasmids, by specific degradation of invader DNA or RNA. However, this involves the risk of autoimmunity if immune memory against host DNA is mistakenly acquired. Such autoimmunity has been shown to be highly toxic in several bacteria and is believed to be one of the major costs of maintaining these defense systems. Here we generated an experimental system in which a non-essential gene, required for pigment production and the reddish colony color, is targeted by the CRISPR-Cas I-B system of the halophilic archaeon Haloferax volcanii...
March 2, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334741/benchmarks-for-measurement-of-duplicate-detection-methods-in-nucleotide-databases
#15
Qingyu Chen, Justin Zobel, Karin Verspoor
Duplication of information in databases is a major data quality challenge. The presence of duplicates, implying either redundancy or inconsistency, can have a range of impacts on the quality of analyses that use the data. To provide a sound basis for research on this issue in databases of nucleotide sequences, we have developed new, large-scale validated collections of duplicates, which can be used to test the effectiveness of duplicate detection methods. Previous collections were either designed primarily to test efficiency, or contained only a limited number of duplicates of limited kinds...
January 8, 2017: Database: the Journal of Biological Databases and Curation
https://www.readbyqxmd.com/read/28334523/transformable-nanomaterials-as-artificial-extracellular-matrix-for-inhibiting-tumor-invasion-and-metastasis
#16
Xiao-Xue Hu, Ping-Ping He, Guo-Bin Qi, Yu-Juan Gao, Yao-Xin Lin, Chao Yang, Pei-Pei Yang, Hongxun Hao, Lei Wang, Hao Wang
Tumor metastasis is one of the big challenges in cancer treatment and is often associated with high patient mortality. Until now, there is an agreement that tumor invasion and metastasis are related to degradation of extracellular matrix (ECM) by enzymes. Inspired by the formation of natural ECM and the in situ self-assembly strategy developed in our group, herein, we in situ constructed an artificial extracellular matrix (AECM) based on transformable Laminin (LN)-mimic peptide 1 (BP-KLVFFK-GGDGR-YIGSR) for inhibition of tumor invasion and metastasis...
March 23, 2017: ACS Nano
https://www.readbyqxmd.com/read/28334484/amine-transaminase-engineering-for-spatially-bulky-substrate-acceptance
#17
Uwe Bornscheuer, Martin S Weiß, Ioannis V Pavlidis, Paul Spur, Steven P Hanlon, Beat Wirz, Hans Iding
Amine transaminase (ATA) catalysing stereoselective amination of prochiral ketones is an attractive alternative to transition metal catalysis. As wild-type ATAs accept only non-sterically hindered ketones, efforts to widen the substrate scope to more challenging targets are of general interest. We recently designed ATAs to accept aromatic and thus planar bulky amines, via a sequenced based motif that supports the identification of novel enzymes. However, these variants were not active against 2,2-dimethyl-1-phenyl-propan-1-one, which carries a spatially bulky tert-butyl substituent adjacent to the carbonyl function...
March 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28334268/an-algorithmic-perspective-of-de-novo-cis-regulatory-motif-finding-based-on-chip-seq-data
#18
Bingqiang Liu, Jinyu Yang, Yang Li, Adam McDermaid, Qin Ma
Transcription factors are proteins that bind to specific DNA sequences and play important roles in controlling the expression levels of their target genes. Hence, prediction of transcription factor binding sites (TFBSs) provides a solid foundation for inferring gene regulatory mechanisms and building regulatory networks for a genome. Chromatin immunoprecipitation sequencing (ChIP-seq) technology can generate large-scale experimental data for such protein-DNA interactions, providing an unprecedented opportunity to identify TFBSs (a...
March 8, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28334262/discriminating-the-reaction-types-of-plant-type-iii-polyketide-synthases
#19
Yugo Shimizu, Hiroyuki Ogata, Susumu Goto
Motivation: Functional prediction of paralogs is challenging in bioinformatics because of rapid functional diversification after gene duplication events combined with parallel acquisitions of similar functions by different paralogs. Plant type III polyketide synthases (PKSs), producing various secondary metabolites, represent a paralogous family that has undergone gene duplication and functional alteration. Currently, there is no computational method available for the functional prediction of type III PKSs...
March 6, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334201/critical-evaluation-of-bioinformatics-tools-for-the-prediction-of-protein-crystallization-propensity
#20
Huilin Wang, Liubin Feng, Geoffrey I Webb, Lukasz Kurgan, Jiangning Song, Donghai Lin
X-ray crystallography is the main tool for structural determination of proteins. Yet, the underlying crystallization process is costly, has a high attrition rate and involves a series of trial-and-error attempts to obtain diffraction-quality crystals. The Structural Genomics Consortium aims to systematically solve representative structures of major protein-fold classes using primarily high-throughput X-ray crystallography. The attrition rate of these efforts can be improved by selection of proteins that are potentially easier to be crystallized...
February 27, 2017: Briefings in Bioinformatics
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