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Dna-encoded library

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https://www.readbyqxmd.com/read/28392906/selection-of-single-chain-variable-fragments-specific-for-mycobacterium-tuberculosis-esat-6-antigen-using-ribosome-display
#1
Shahrzad Ahangarzadeh, Mojgan Bandehpour, Bahram Kazemi
OBJECTIVES: Tuberculosis (TB) is still one of the problematic infectious diseases in developing countries, especially in Iran. In the present study, we applied ribosome display technique to select single chain variable fragments (scFvs) specific for the 6-kDa early secretory antigenic target (ESAT-6) antigen of Mycobacterium tuberculosis from a mouse scFv library. MATERIALS AND METHODS: The gene encoding ESAT-6 was cloned into pET22b(+) plasmid and expressed in Escherichia coli BL21 (DE3)...
March 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28384204/cloning-expression-and-antioxidant-activity-of-a-thioredoxin-peroxidase-from-branchiostoma-belcheri-tsingtaunese
#2
Jian Liao, Kaiyu Wang, Weirong Yao, Xunfei Yi, Huihui Yan, Min Chen, Xiaopeng Lan
Peroxiredoxins (Prxs) are ubiquitous antioxidant enzymes that catalyze the thioredoxin- dependent reduction of hydroperoxides. In this study, a novel thioredoxin peroxidase (Bbt-TPx1), a member of the peroxiredoxin superfamily, was found by EST sequence analysis of a cDNA library of Branchiostoma belcheri tsingtaunese ovary. The sequence of a full-length cDNA clone contained an open reading frame encoding a polypeptide of 198 amino acid residues, with a calculated molecular weight of 22,150 Da. The expression patterns of the protein at different developmental stages and adult amphioxus tissues indicate that this enzyme may play important roles in anti-oxidation and innate immunity...
2017: PloS One
https://www.readbyqxmd.com/read/28377530/topoisomerase-ii-inhibitors-induce-dna-damage-dependent-interferon-responses-circumventing-ebola-virus-immune-evasion
#3
Priya Luthra, Sebastian Aguirre, Benjamin C Yen, Colette A Pietzsch, Maria T Sanchez-Aparicio, Bersabeh Tigabu, Lorraine K Morlock, Adolfo García-Sastre, Daisy W Leung, Noelle S Williams, Ana Fernandez-Sesma, Alexander Bukreyev, Christopher F Basler
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28370935/methylphosphonate-metabolism-by-pseudomonas-sp-populations-contributes-to-the-methane-oversaturation-paradox-in-an-oxic-freshwater-lake
#4
Qian Wang, John E Dore, Timothy R McDermott
The "CH4 oversaturation paradox" has been observed in oxygen-rich marine and lake waters, and viewed to significantly contribute to biosphere cycling of methane, a potent greenhouse gas. Our study focused on the intriguing well-defined pelagic methane enriched zone (PMEZ) in freshwater lakes. Spiking Yellowstone Lake PMEZ samples with (13) C-labeled potential methanogenesis substrates found only (13) C-methylphosphonate (MPn) resulted in (13) CH4 generation. In 16S rRNA gene Illumina libraries, four Pseudomonas sp...
April 3, 2017: Environmental Microbiology
https://www.readbyqxmd.com/read/28370162/simultaneous-human-platelet-antigen-genotyping-and-detection-of-novel-single-nucleotide-polymorphisms-by-targeted-next-generation-sequencing
#5
Sue Davey, Cristina Navarrete, Colin Brown
BACKGROUND: Twenty-nine human platelet antigen systems have been described to date, but the majority of current genotyping methods are restricted to the identification of those most commonly associated with alloantibody production in a clinical context. This can result in a protracted investigation if causative human platelet antigens are rare or novel. A targeted next-generation sequencing approach was designed to detect all known human platelet antigens with the additional capability of identifying novel mutations in the encoding genes...
March 28, 2017: Transfusion
https://www.readbyqxmd.com/read/28360095/hnrnpll-a-newly-identified-colorectal-cancer-metastasis-suppressor-modulates-alternative-splicing-of-cd44-during-epithelial-mesenchymal-transition
#6
Keiichiro Sakuma, Eiichi Sasaki, Kenya Kimura, Koji Komori, Yasuhiro Shimizu, Yasushi Yatabe, Masahiro Aoki
OBJECTIVE: Despite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis. DESIGN: CMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA...
March 30, 2017: Gut
https://www.readbyqxmd.com/read/28356959/effect-of-cancer-testis-antigen-ny-sar-35-on-the-proliferation-migration-and-invasion-of-cancer-cells
#7
Myung-Ha Song, Ye-Rin Kim, Jae-Ho Bae, Chang-Hun Lee, Sang-Yull Lee
NY-SAR-35 is a cancer/testis (CT) antigen that was identified by serological analysis of recombinant complementary DNA expression libraries. The gene encoding NY-SAR-35 is located on the × chromosome and is aberrantly expressed in a number of cancer types and germ cells, such as those in the testes, but not in normal tissue. It has been reported that treatment with a demethylating agent induced the expression of NY-SAR-35 in several types of cancer cells. However, the function of NY-SAR-35 in cancer remains undetermined...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28350959/mapping-of-drug-like-chemical-universe-with-reduced-complexity-molecular-frameworks
#8
Aleksejs Kontijevskis
The emergence of the DNA-encoded chemical libraries (DEL) field in the past decade has attracted the attention of the pharmaceutical industry as a powerful mechanism for the discovery of novel drug-like hits for various biological targets. Nuevolution Chemetics technology enables DNA-encoded synthesis of billions of chemically diverse drug-like small molecule compounds, and the efficient screening and optimization of these, facilitating effective identification of drug candidates at an unprecedented speed and scale...
April 12, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28340408/ongoing-evolution-of-pseudomonas-aeruginosa-pao1-sublines-complicates-studies-of-dna-damage-repair-and-tolerance
#9
Julia Sidorenko, Tatjana Jatsenko, Maia Kivisaar
Sublines of the major P. aeruginosa reference strain PAO1 are derivatives of the original PAO1 isolate, which are maintained in laboratories worldwide. These sublines display substantial genomic and phenotypic variation due to ongoing microevolution. Here, we examined four sublines, MPAO1, PAO1-L, PAO1-DSM and PAO1-UT, originated from different laboratories, and six DNA polymerase-deficient mutants from the P. aeruginosa MPAO1 transposon library for their employment in elucidation of DNA damage repair and tolerance mechanisms in P...
March 16, 2017: Mutation Research
https://www.readbyqxmd.com/read/28331161/isolation-of-cyanobacterial-mutants-exhibiting-growth-defects-under-microoxic-conditions-by-transposon-tagging-mutagenesis-of-synechocystis-sp-pcc-6803
#10
Kazuki Terauchi, Riho Sobue, Yuho Furutani, Rina Aoki, Yuichi Fujita
Cyanobacteria are photosynthetic prokaryotes that perform oxygenic photosynthesis by extracting electrons from water, with the generation of oxygen as a byproduct. Cyanobacteria use oxygen not only for respiration to produce energy in the dark but also for biosynthesis of various metabolites, such as heme and chlorophyll. Oxygen levels dynamically fluctuate in the field environments, from hyperoxic at daytime to almost anaerobic at night. Thus, adaptation to anaerobiosis should be important for cyanobacteria to survive in low-oxygen and anaerobic environments...
March 22, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/28328323/an-adaptable-high-throughput-technology-enabling-the-identification-of-specific-transcription-modulators
#11
Tim Bergbrede, Emily Hoberg, Nils-Göran Larsson, Maria Falkenberg, Claes M Gustafsson
Mitochondria harbor the oxidative phosphorylation (OXPHOS) system, which under aerobic conditions produces the bulk of cellular adenosine triphosphate (ATP). The mitochondrial genome encodes key components of the OXPHOS system, and it is transcribed by the mitochondrial RNA polymerase, POLRMT. The levels of mitochondrial transcription correlate with the respiratory activity of the cell. Therefore, compounds that can increase or decrease mitochondrial gene transcription may be useful for fine-tuning metabolism and could be used to treat metabolic diseases or certain forms of cancer...
April 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28318088/twenty-five-years-of-dna-encoded-chemical-libraries
#12
EDITORIAL
Dario Neri
Reference library: The availability of DNA-encoded chemical libraries containing billions of compounds facilitates the discovery of binding molecules for pharmaceutical applications and for investigating biological processes. This Special Issue highlights the use of this library technology and some of the latest developments in the field.
March 20, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28287689/analysis-of-current-dna-encoded-library-screening-data-indicates-higher-false-negative-rates-for-numerically-larger-libraries
#13
Alexander L Satz, Remo Hochstrasser, Ann C Petersen
To optimize future DNA-encoded library design, we have attempted to quantify the library size at which the signal becomes undetectable. To accomplish this we (i) have calculated that percent yields of individual library members following a screen range from 0.002 to 1%, (ii) extrapolated that ∼1 million copies per library member are required at the outset of a screen, and (iii) from this extrapolation predict that false negative rates will begin to outweigh the benefit of increased diversity at library sizes >10(8)...
March 17, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28287381/a-preliminary-evaluation-of-next-generation-sequencing-as-a-screening-tool-for-targeted-genotyping-of-erythrocyte-and-platelet-antigens-in-blood-donors
#14
Agnieszka Orzińska, Katarzyna Guz, Michał Mikula, Maria Kulecka, Anna Kluska, Aneta Balabas, Monika Pelc-Kłopotowska, Jerzy Ostrowski, Ewa Brojer
BACKGROUND: Matching the compatibility of donor blood with the recipient's antigens prevents alloimmunisation. Next-generation sequencing (NGS) technology is a promising method for extensive blood group and platelet antigen genotyping of blood donors. It circumvents the limitations of detecting known alleles based on predefined polymorphisms and enables targeted sequencing on a massive scale. The aim of this study was to evaluate the NGS AmpliSeq application on the Ion Torrent platform as a screening tool for genotyping blood donors' erythrocyte/platelet antigens...
March 10, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28281333/discovering-drugs-with-dna-encoded-library-technology-from-concept-to-clinic-with-an-inhibitor-of-soluble-epoxide-hydrolase
#15
Svetlana Belyanskaya, Yun Ding, James Callahan, Aili Lazaar, David Israel
DNA encoded chemical library technology was developed with the vision of becoming a transformational platform for drug discovery. The hope was that a new screening paradigm for low molecular weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information encoding attributes of DNA, the power of molecular biology and a streamlined selection-based discovery process. We describe the discovery and early clinical development of GSK2256294, an inhibitor of the enzyme soluble epoxide hydrolase (sEH, EPHX2) using Encoded Library Technology (ELT)...
March 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28277838/using-natural-products-for-drug-discovery-the-impact-of-the-genomics-era
#16
Mingzi M Zhang, Yuan Qiao, Ee Lui Ang, Huimin Zhao
Evolutionarily selected over billions of years for their interactions with biomolecules, natural products have been and continue to be a major source of pharmaceuticals. In the 1990s, pharmaceutical companies scaled down their natural product discovery programs in favor of synthetic chemical libraries due to major challenges such as high rediscovery rates, challenging isolation, and low production titers. Propelled by advances in DNA sequencing and synthetic biology technologies, insights into microbial secondary metabolism provided have inspired a number of strategies to address these challenges...
March 14, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28276654/a-family-13-thioesterase-isolated-from-an-activated-sludge-metagenome-insights-into-aromatic-compounds-metabolism
#17
Ayixon Sánchez-Reyez, Ramón Alberto Batista-García, Gilberto Valdés-García, Ernesto Ortiz, Lucía Perezgasga, Andrés Zárate-Romero, Nina Pastor, Jorge Luis Folch-Mallol
Activated sludge is produced during the treatment of sewage and industrial wastewaters. Its diverse chemical composition allows growth of a large collection of microbial phylotypes with very different physiologic and metabolic profiles. Thus, activated sludge is considered as an excellent environment to discover novel enzymes through functional metagenomics, especially activities related with degradation of environmental pollutants. Metagenomic DNA was isolated and purified from an activated sludge sample. Metagenomic libraries were subsequently constructed in Escherichia coli...
March 9, 2017: Proteins
https://www.readbyqxmd.com/read/28273103/functional-metagenomics-reveals-novel-%C3%AE-galactosidases-not-predictable-from-gene-sequences
#18
Jiujun Cheng, Tatyana Romantsov, Katja Engel, Andrew C Doxey, David R Rose, Josh D Neufeld, Trevor C Charles
The techniques of metagenomics have allowed researchers to access the genomic potential of uncultivated microbes, but there remain significant barriers to determination of gene function based on DNA sequence alone. Functional metagenomics, in which DNA is cloned and expressed in surrogate hosts, can overcome these barriers, and make important contributions to the discovery of novel enzymes. In this study, a soil metagenomic library carried in an IncP cosmid was used for functional complementation for β-galactosidase activity in both Sinorhizobium meliloti (α-Proteobacteria) and Escherichia coli (γ-Proteobacteria) backgrounds...
2017: PloS One
https://www.readbyqxmd.com/read/28263788/discovery-of-a-novel-oocyte-specific-kr%C3%A3-ppel-associated-box-domain-containing-zinc-finger-protein-required-for-early-embryogenesis-in-cattle
#19
Jacqelyn M Hand, Kun Zhang, Lei Wang, Prasanthi P Koganti, Kristen Mastrantoni, Sandeep K Rajput, Mohamed Ashry, George W Smith, Jianbo Yao
Zinc finger (ZNF) transcription factors interact with DNA through zinc finger motifs and play important roles in a variety of cellular functions including cell growth, proliferation, development, apoptosis, and intracellular signal transduction. One-third of ZNF proteins in metazoans contain a highly conserved N-terminal motif known as the Krüppel-associated box (KRAB) domain, which acts as a potent, DNA-binding dependent transcriptional repression module. Analysis of RNA-Seq data generated from a bovine oocyte cDNA library identified a novel transcript, which encodes a KRAB-containing ZNF transcription factor (named ZNFO)...
March 2, 2017: Mechanisms of Development
https://www.readbyqxmd.com/read/28249011/transposon-insertion-libraries-for-the-characterization-of-mutants-from-the-kiwifruit-pathogen-pseudomonas-syringae-pv-actinidiae
#20
Carl H Mesarich, Jonathan Rees-George, Paul P Gardner, Fatemeh Ashari Ghomi, Monica L Gerth, Mark T Andersen, Erik H A Rikkerink, Peter C Fineran, Matthew D Templeton
Pseudomonas syringae pv. actinidiae (Psa), the causal agent of kiwifruit canker, is one of the most devastating plant diseases of recent times. We have generated two mini-Tn5-based random insertion libraries of Psa ICMP 18884. The first, a 'phenotype of interest' (POI) library, consists of 10,368 independent mutants gridded into 96-well plates. By replica plating onto selective media, the POI library was successfully screened for auxotrophic and motility mutants. Lipopolysaccharide (LPS) biosynthesis mutants with 'Fuzzy-Spreader'-like morphologies were also identified through a visual screen...
2017: PloS One
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