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https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#1
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149299/twj-screen-an-isothermal-screening-assay-to-assess-ligand-dna-junction-interactions-in-vitro
#2
Ludivine Guyon, Marc Pirrotta, Katerina Duskova, Anton Granzhan, Marie-Paule Teulade-Fichou, David Monchaud
The quest for chemicals able to operate at selected genomic loci in a spatiotemporally controlled manner is desirable to create manageable DNA damages. Mounting evidence now shows that alternative DNA structures, including G-quadruplexes and branched DNA (or DNA junctions), might hamper proper progression of replication fork, thus triggering DNA damages and genomic instability. Therefore, small molecules that stabilize these DNA structures are currently scrutinized as a promising way to create genomic defects that cannot be dealt with properly by cancer cells...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29149199/epidemiology-and-clinical-profile-of-pathogens-responsible-for-the-hospitalization-of-children-in-sousse-area-tunisia
#3
Ines Brini, Aida Guerrero, Naila Hannachi, Jihene Bouguila, Dorothea Orth-Höller, Amira Bouhlel, Lamia Boughamoura, Benjamin Hetzer, Wegene Borena, Britta Schiela, Dorothee Von Laer, Jalel Boukadida, Heribert Stoiber
This study aimed to identify a broad spectrum of respiratory pathogens from hospitalized and not-preselected children with acute respiratory tract infections in the Farhat Hached University-hospital of Sousse, Tunisia. Between September 2013 and December 2014, samples from 372 children aged between 1 month and 5 years were collected, and tested using multiplex real-time RT-PCR by a commercial assay for 21 respiratory pathogens. In addition, samples were screened for the presence of Streptococcus pneumoniae 16S rDNA using real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/29148755/novel-anti-tubercular-6-dialkylaminopyrimidine-carboxamides-from-phenotypic-whole-cell-high-throughput-screening-of-a-softfocus-library-structure-activity-relationship-and-target-identification-studies
#4
Colin R Wilson, Richard K Gessner, Atica Moosa, Ronnett Seldon, Digby F Warner, Valerie Mizrahi, Candice Soares de Melo, Sandile B Simelane, Aloysius T Nchinda, Efrem Abay, Dale Taylor, Mathew Njoroge, Christel Brunschwig, Nina Lawrence, Helena I M Boshoff, Clifton E Barry, Frederick A Sirgel, Paul van Helden, C John Harris, Richard Gordon, Sonja Ghidelli-Disse, Hannah Pflaumer, Markus Boesche, Gerard Drewes, Olalla Sanz, Gracia Santos, Maria José Rebollo-Lopez, Beatriz Urones, Carolyn Selenski, Maria Jose Lafuente-Monasterio, Matthew Axtman, Joël Lelièvre, Lluis Ballell, Rudolf Mueller, Leslie J Street, Sandeep R Ghorpade, Kelly Chibale
A BioFocus DPI SoftFocus library of ~35,000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with anti-tubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell-wall homeostasis, and DNA damage. Among the hits which passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29148714/evaluating-the-rate-and-substrate-specificity-of-laboratory-evolved-xna-polymerases
#5
Ali Nikoomanzar, Matthew R Dunn, John C Chaput
Engineered polymerases that can copy genetic information between DNA and xeno-nucleic acids (XNA) hold tremendous value as reagents in future bio-technology applications. However, current XNA poly-merases function with inferior activity relative to their natural counterparts, indicating that current polymerase engineering efforts would benefit from new benchmark-ing assays. Here, we describe a highly parallel, low cost method for measuring the average rate and substrate specificity of XNA polymerases in a standard qPCR instrument...
November 17, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29147535/a-platform-for-high-throughput-screening-of-dna-encoded-catalyst-libraries-in-organic-solvents
#6
K Delaney Hook, John T Chambers, Ryan Hili
We have developed a novel high-throughput screening platform for the discovery of small-molecules catalysts for bond-forming reactions. The method employs an in vitro selection for bond-formation using amphiphilic DNA-encoded small molecules charged with reaction substrate, which enables selections to be conducted in a variety of organic or aqueous solvents. Using the amine-catalysed aldol reaction as a catalytic model and high-throughput DNA sequencing as a selection read-out, we demonstrate the 1200-fold enrichment of a known aldol catalyst from a library of 16...
October 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29147003/real-time-wash-free-detection-of-unlabeled-pna-dna-hybridization-using-discrete-fet-sensor
#7
Matti Kaisti, Anssi Kerko, Eero Aarikka, Petri Saviranta, Zhanna Boeva, Tero Soukka, Ari Lehmusvuori
We demonstrate an electrochemical sensor for detection of unlabeled single-stranded DNA using peptide nucleic acid (PNA) probes coupled to the field-effect transistor (FET) gate. The label-free detection relies on the intrinsic charge of the DNA backbone. Similar detection schemes have mainly concentrated on sensitivity improvement with an emphasis on new sensor structures. Our approach focuses on using an extended-gate that separates the FET and the sensing electrode yielding a simple and mass fabricable device...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146914/cat-d-a-targeted-sequencing-method-for-the-simultaneous-detection-of-small-dna-mutations-and-large-dna-deletions-with-flexible-boundaries
#8
Ru Hong, Udita Chandola, Li-Feng Zhang
We developed a targeted DNA sequencing method that is capable of detecting a comprehensive panel of DNA mutations including small DNA mutations and large DNA deletions with unknown/flexible boundaries. The method directly identifies the large DNA deletions (Cat-D) without relying on sequencing coverage to make the genotype calls. We performed the method to simultaneously detect 10 small DNA mutations in β-thalassemia and 2 large genomic deletions in α-thalassemia from 10 genomic DNA samples. Cat-D was performed on 8 genomic DNA samples in duplicate...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146902/single-molecule-multiplexed-nanopore-protein-screening-in-human-serum-using-aptamer-modified-dna-carriers
#9
Jasmine Y Y Sze, Aleksandar P Ivanov, Anthony E G Cass, Joshua B Edel
The capability to screen a range of proteins at the single-molecule level with enhanced selectivity in biological fluids has been in part a driving force in developing future diagnostic and therapeutic strategies. The combination of nanopore sensing and nucleic acid aptamer recognition comes close to this ideal due to the ease of multiplexing, without the need for expensive labelling methods or extensive sample pre-treatment. Here, we demonstrate a fully flexible, scalable and low-cost detection platform to sense multiple protein targets simultaneously by grafting specific sequences along the backbone of a double-stranded DNA carrier...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146883/a-landscape-of-germline-mutations-in-a-cohort-of-inherited-bone-marrow-failure-patients
#10
Olivier Bluteau, Marie Sebert, Thierry Leblanc, Régis Peffault de Latour, Samuel Quentin, Elodie Lainey, Lucie Hernandez, Jean-Hugues Dalle, Flore Sicre de Fontbrune, Etienne Lengline, Raphael Itzykson, Emmanuelle Clappier, Nicolas Boissel, Naddia Vasquez, Mélanie Da Costa, Julien Masliah-Planchon, Wendy Cuccuini, Anna Raimbault, Louis De Jaegere, Lionel Adès, Pierre Fenaux, Sébastien Maury, Claudine Schmitt, Marc Muller, Carine Domenech, Nicolas Blin, Bénédicte Bruno, Isabelle Pellier, Mathilde Hunault, Stéphane Blanche, Arnaud Petit, Guy Leverger, Gérard Michel, Yves Bertrand, André Baruchel, Gérard Socié, Jean Soulier
Bone marrow failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% bone marrow blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germline mutation in 86 patients (48...
November 16, 2017: Blood
https://www.readbyqxmd.com/read/29146476/mutation-screening-of-the-glis3-gene-in-a-cohort-of-592-chinese-patients-with-congenital-hypothyroidism
#11
Chunyun Fu, Shiyu Luo, Xigui Long, Yingfeng Li, Shangyang She, Xuehua Hu, Meizhen Mo, Zhanghong Wang, Yuhua Chen, Chun He, Jiasun Su, Yue Zhang, Fei Lin, Bobo Xie, Qifei Li, Shaoke Chen
OBJECTIVES: Defects in the human GLI-similar 3 (GLIS3) gene are reported to be a rare cause of congenital hypothyroidism (CH) and neonatal diabetes. The aim of this study was to examine the prevalence of GLIS3 mutation among CH patients in the Guangxi Zhuang Autonomous Region of China and to define the relationships between GLIS3 genotypes and clinical phenotypes. METHODS: Blood samples were collected from 592 patients with CH in Guangxi Zhuang Autonomous Region, China, and genomic DNA was extracted from peripheral blood leukocytes...
November 13, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/29145860/a-new-single-step-protocol-for-rapid-baculovirus-driven-protein-production-in-insect-cells
#12
Judith Scholz, Sabine Suppmann
BACKGROUND: In the last three decades, the Baculovirus expression vector system (BEV) has evolved to one of the most widely used eukaryotic systems for heterologous protein expression including approved vaccines and therapies. Despite the significant improvements introduced during the past years, the BEV system still has major drawbacks, primarily the time required to generate recombinant virus and virus instability for certain target proteins. In this study we show that the conventional method to generate recombinant Baculovirus using a Tn7 transposition based system can be shortened to a single-step transfection-only procedure without further amplification...
November 16, 2017: BMC Biotechnology
https://www.readbyqxmd.com/read/29143652/genetic-profiles-of-ten-dirofilaria-immitis-isolates-susceptible-or-resistant-to-macrocyclic-lactone-heartworm-preventives
#13
Catherine Bourguinat, Kathy Keller, Jianguo Xia, Pierre Lepage, Tom L McTier, Debra J Woods, Roger K Prichard
BACKGROUND: For dogs and cats, chemoprophylaxis with macrocyclic lactone (ML) preventives for heartworm disease is widely used in the United States and other countries. Since 2005, cases of loss of efficacy (LOE) of heartworm preventives have been reported in the U.S. More recently, ML-resistant D. immitis isolates were confirmed. Previous work identified 42 genetic markers that could predict ML response in individual samples. For field surveillance, it would be more appropriate to work on microfilarial pools from individual dogs with a smaller subset of genetic markers...
November 9, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/29143601/morphological-description-and-dna-barcoding-study-of-sand-rice-agriophyllum-squarrosum-chenopodiaceae-collected-in-kazakhstan
#14
Yuliya Genievskaya, Saule Abugalieva, Aibatsha Zhubanysheva, Yerlan Turuspekov
BACKGROUND: Sand rice (Agriophyllum squarrosum (L.) Moq.) is an annual shrub-like plant adapted to the mobile sand dunes in desert and semi-desert regions of Asia. It has a balanced nutrient composition with relatively high concentration of lipids and proteins, which results in its nutrition being similar to legumes. Sand rice's proteins contain the full range of essential amino acids. However, calories content is more similar to wheat. These features together with desert stress resistance make sand rice a potential food crop resilient to ongoing climate change...
November 14, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29143101/candidate-biomarkers-in-the-cervical-vaginal-fluid-for-the-self-diagnosis-of-cervical-precancer
#15
REVIEW
Xaveer Van Ostade, Martin Dom, Wiebren Tjalma, Geert Van Raemdonck
PURPOSE: Despite improvement in vaccines against human papilloma virus (HPV), the causative agent of cervical cancer, screening women for cervical precancer will remain indispensable in the coming 30-40 years. A simple test that could be performed at home or at a doctor's practice and that informs the woman whether she is at risk would significantly help make a broader group of patients who aware that they need medical treatment. Cervical vaginal fluid (CVF) is a body fluid that is very well suited for such a test...
November 15, 2017: Archives of Gynecology and Obstetrics
https://www.readbyqxmd.com/read/29142517/is-methylation-analysis-of-sfrp2-tfpi2-ndrg4-and-bmp3-promoters-suitable-for-colorectal-cancer-screening-in-the-korean-population
#16
Soo-Kyung Park, Hae Lim Baek, Junghee Yu, Ji Yeon Kim, Hyo-Joon Yang, Yoon Suk Jung, Kyu Yong Choi, Hungdai Kim, Hyung Ook Kim, Kyung Uk Jeong, Ho-Kyung Chun, Kyungeun Kim, Dong Il Park
Background/Aims: Colorectal cancer (CRC) screening using stool DNA was recently found to yield good detection rates. A multi-target stool DNA test (Cologuard®, Exact Sciences), including methylated genes has been recently approved by the U.S. Food and Drug Administration. The aim of this study was to validate these aberrantly methylated genes as stool-based DNA markers for detecting CRC and colorectal advanced adenoma (AA) in the Korean population. Methods: A single-center study was conducted in 36 patients with AA; 35 patients with CRC; and 40 endoscopically diagnosed healthy controls using CRC screening colonoscopy...
October 2017: Intestinal Research
https://www.readbyqxmd.com/read/29141509/relative-morphokinetics-assessed-by-time-lapse-imaging-are-altered-in-embryos-from-patients-with-endometriosis
#17
Alexander Freis, Jens Erik Dietrich, Moritz Binder, Verena Holschbach, Thomas Strowitzki, Ariane Germeyer
INTRODUCTION: Time-lapse technology allows almost continuous noninvasive assessment of embryonic development. It was shown previously that relative kinetics defining cleavage synchronicity are better predictors of blastocyst quality than absolute time points. This study aims to compare relative kinetics in embryos from patients with and without endometriosis. METHODS: Time-lapse data were collected retrospectively from 596 patients undergoing infertility treatment for in vitro fertilization from January 2011 to July 2016...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/29141033/transcriptome-profiling-of-claw-muscle-of-the-mud-crab-scylla-paramamosain-at-different-fattening-stages
#18
Qingling Jiang, Chenchang Bao, Ya'nan Yang, An Liu, Fang Liu, Huiyang Huang, Haihui Ye
In crustaceans, muscle growth and development is complicated, and to date substantial knowledge gaps exist. In this study, the claw muscle, hepatopancreas and nervous tissue of the mud crab (Scylla paramamosain) were collected at three fattening stages for sequence by the Illumina sequencing. A total of 127.87 Gb clean data with no less than 3.94 Gb generated for each sample and the cycleQ30 percentages were more than 86.13% for all samples. De Bruijn assembly of these clean data produced 94,853 unigenes, thereinto, 50,059 unigenes were found in claw muscle...
2017: PloS One
https://www.readbyqxmd.com/read/29140506/quantification-of-the-effect-of-toxicants-on-the-intracellular-kinetic-energy-and-cross-sectional-area-of-mammary-epithelial-organoids-by-oct-fluctuation-spectroscopy
#19
Xiao Yu, Ashley M Fuller, Richard Blackmon, Melissa A Troester, Amy L Oldenburg
The ability to assess toxicant exposures of three-dimensional (3D) in vitro mammary models that recapitulate the tissue microenvironment can aid in our understanding of environmental exposure risk over time. Longitudinal studies of 3D model systems, however, are cumbersome and suffer from a lack of high-throughput toxicological assays. In this study, we establish a noninvasive and label-free optical coherence tomography (OCT)-based imaging platform for tracking exposure-response relationships in 3D human mammary epithelial organoid models...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29139600/arcr-modulates-biofilm-formation-in-the-dental-plaque-colonizer-streptococcus-gordonii
#20
Jill C Robinson, Nadia Rostami, John Casement, Waldemar Vollmer, Alexander H Rickard, Nicholas S Jakubovics
Biofilm formation and cell-cell sensing by the pioneer dental plaque coloniser Streptococcus gordonii is dependent upon arginine. This study aimed to identify genetic factors linking arginine-dependent responses and biofilm formation in S. gordonii. Isogenic mutants disrupted in genes required for biosynthesis or catabolism of arginine, or for arginine-dependent gene regulation, were screened for their ability to form biofilms in a static culture model. Biofilm formation by a knockout mutant of arcR, encoding an arginine-dependent regulator of transcription, was reduced to <50% that of the wild-type whereas other strains were unaffected...
November 15, 2017: Molecular Oral Microbiology
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