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https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#1
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28079151/discovery-and-mechanistic-characterization-of-selective-inhibitors-of-h2s-producing-enzyme-3-mercaptopyruvate-sulfurtransferase-3mst-targeting-active-site-cysteine-persulfide
#2
Kenjiro Hanaoka, Kiyoshi Sasakura, Yusuke Suwanai, Sachiko Toma-Fukai, Kazuhito Shimamoto, Yoko Takano, Norihiro Shibuya, Takuya Terai, Toru Komatsu, Tasuku Ueno, Yuki Ogasawara, Yukihiro Tsuchiya, Yasuo Watanabe, Hideo Kimura, Chao Wang, Masanobu Uchiyama, Hirotatsu Kojima, Takayoshi Okabe, Yasuteru Urano, Toshiyuki Shimizu, Tetsuo Nagano
Very recent studies indicate that sulfur atoms with oxidation state 0 or -1, called sulfane sulfurs, are the actual mediators of some physiological processes previously considered to be regulated by hydrogen sulfide (H2S). 3-Mercaptopyruvate sulfurtransferase (3MST), one of three H2S-producing enzymes, was also recently shown to produce sulfane sulfur (H2Sn). Here, we report the discovery of several potent 3MST inhibitors by means of high-throughput screening (HTS) of a large chemical library (174,118 compounds) with our H2S-selective fluorescent probe, HSip-1...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077314/biological-or-pharmacological-activation-of-protein-kinase-c-alpha-constrains-hepatitis-e-virus-replication
#3
Wenshi Wang, Yijin Wang, Yannick Debing, Xinying Zhou, Yuebang Yin, Lei Xu, Elena Herrera Carrillo, Johannes H Brandsma, Raymond A Poot, Ben Berkhout, Johan Neyts, Maikel P Peppelenbosch, Qiuwei Pan
Although hepatitis E has emerged as a global health issue, there is limited knowledge of its infection biology and no FDA-approved medication is available. Aiming to investigate the role of protein kinases in hepatitis E virus (HEV) infection and to identify potential antiviral targets, we screened a library of pharmacological kinase inhibitors in a cell culture model, a subgenomic HEV replicon containing luciferase reporter. We identified protein kinase C alpha (PKCα) as an essential cell host factor restricting HEV replication...
January 8, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28077258/discovery-of-new-mura-inhibitors-using-induced-fit-simulation-and-docking
#4
Kaja Rožman, Samo Lešnik, Boris Brus, Martina Hrast, Matej Sova, Delphine Patin, Hélène Barreteau, Janez Konc, Dušanka Janežič, Stanislav Gobec
We report on the successful application of ProBiS-CHARMMing web server in the discovery of new inhibitors of MurA, an enzyme that catalyzes the first committed cytoplasmic step of bacterial peptidoglycan synthesis. The available crystal structures of Escherichia coli MurA in the Protein Data Bank have binding sites whose small volume does not permit the docking of drug-like molecules. To prepare the binding site for docking, the ProBiS-CHARMMing web server was used to simulate the induced-fit effect upon ligand binding to MurA, resulting in a larger, more holo-like binding site...
December 31, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28074328/lipidpioneer-a-comprehensive-user-generated-exact-mass-template-for-lipidomics
#5
Candice Z Ulmer, Jeremy P Koelmel, Jared M Ragland, Timothy J Garrett, John A Bowden
Lipidomics, the comprehensive measurement of lipid species in a biological system, has promising potential in biomarker discovery and disease etiology elucidation. Advances in chromatographic separation, mass spectrometric techniques, and novel substrate applications continue to expand the number of lipid species observed. The total number and type of lipid species detected in a given sample are generally indicative of the sample matrix examined (e.g., serum, plasma, cells, bacteria, tissue, etc.). Current exact mass lipid libraries are static and represent the most commonly analyzed matrices...
January 10, 2017: Journal of the American Society for Mass Spectrometry
https://www.readbyqxmd.com/read/28073790/clemizole-and-modulators-of-serotonin-signalling-suppress-seizures-in-dravet-syndrome
#6
Aliesha Griffin, Kyla R Hamling, Kelly Knupp, SoonGweon Hong, Luke P Lee, Scott C Baraban
Dravet syndrome is a catastrophic childhood epilepsy with early-onset seizures, delayed language and motor development, sleep disturbances, anxiety-like behaviour, severe cognitive deficit and an increased risk of fatality. It is primarily caused by de novo mutations of the SCN1A gene encoding a neuronal voltage-activated sodium channel. Zebrafish with a mutation in the SCN1A homologue recapitulate spontaneous seizure activity and mimic the convulsive behavioural movements observed in Dravet syndrome. Here, we show that phenotypic screening of drug libraries in zebrafish scn1 mutants rapidly and successfully identifies new therapeutics...
January 10, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28071740/elucidating-the-modes-of-action-for-bioactive-compounds-in-a-cell-specific-manner-by-large-scale-chemically-induced-transcriptomics
#7
Michio Iwata, Ryusuke Sawada, Hiroaki Iwata, Masaaki Kotera, Yoshihiro Yamanishi
The identification of the modes of action of bioactive compounds is a major challenge in chemical systems biology of diseases. Genome-wide expression profiling of transcriptional responses to compound treatment for human cell lines is a promising unbiased approach for the mode-of-action analysis. Here we developed a novel approach to elucidate the modes of action of bioactive compounds in a cell-specific manner using large-scale chemically-induced transcriptome data acquired from the Library of Integrated Network-based Cellular Signatures (LINCS), and analyzed 16,268 compounds and 68 human cell lines...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28070575/network-pharmacology-based-virtual-screening-of-natural-products-from-clerodendrum-species-for-identification-of-novel-anti-cancer-therapeutics
#8
Barbi Gogoi, Dhrubajyoti Gogoi, Yumnam Silla, Bibhuti Bhushan Kakoti, Brijmohan Singh Bhau
Plant-derived natural products (NPs) play a vital role in the discovery of new drug molecules and these are used for development of novel therapeutic drugs for a specific disease target. Literature review suggests that natural products possess strong inhibitory efficacy against various types of cancer cells. Clerodendrum indicum and Clerodendrum serratum are reported to have anticancer activity; therefore a study was carried out to identify selective anticancer agents from these plants species. In this report, we employed a docking weighted network pharmacological approach to understand the multi-therapeutics potentiality of C...
January 10, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28064478/automated-phase-mapping-with-agilefd-and-its-application-to-light-absorber-discovery-in-the-v-mn-nb-oxide-system
#9
Santosh K Suram, Yexiang Xue, Junwen Bai, Ronan Le Bras, Brendan Rappazzo, Richard Bernstein, Johan Bjorck, Lan Zhou, R Bruce van Dover, Carla P Gomes, John M Gregoire
Rapid construction of phase diagrams is a central tenet of combinatorial materials science with accelerated materials discovery efforts often hampered by challenges in interpreting combinatorial X-ray diffraction data sets, which we address by developing AgileFD, an artificial intelligence algorithm that enables rapid phase mapping from a combinatorial library of X-ray diffraction patterns. AgileFD models alloying-based peak shifting through a novel expansion of convolutional nonnegative matrix factorization, which not only improves the identification of constituent phases but also maps their concentration and lattice parameter as a function of composition...
January 9, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28060302/a-platform-of-anti-biofilm-assays-suited-to-the-exploration-of-natural-compound-libraries
#10
Malena E Skogman, Pia M Vuorela, Adyary Fallarero
Biofilms are regarded as one of the most challenging topics of modern biomedicine, and they are potentially responsible for over 80% of antibiotic-tolerant infections. Biofilms have displayed an exceptionally high tolerance for chemotherapy, which is thought to be multifactorial. For instance, the matrix provides a physical barrier that decreases the penetration of antibiotics into the biofilm. Also, cells within the biofilms are phenotypically diverse. Likely, biofilm resilience arises from a combination of these and other, yet unknown, mechanisms...
December 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057679/spot-ligand-2-improving-structure-based-virtual-screening-by-binding-homology-search-on-an-expanded-structural-template-library
#11
Thomas Litfin, Yaoqi Zhou, Yuedong Yang
MOTIVATION: The high cost of drug discovery motivates the development of accurate virtual screening tools. Binding-homology, which takes advantage of known protein-ligand binding pairs, has emerged as a powerful discrimination technique. In order to exploit all available binding data, modelled structures of ligand-binding sequences may be used to create an expanded structural binding template library. RESULTS: SPOT-Ligand 2 has demonstrated significantly improved screening performance over its previous version by expanding the template library 15 times over the previous one...
January 5, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28056857/upregulation-of-mrps18a-in-breast-cancer-identified-by-selecting-phage-antibody-libraries-on-breast-tissue-sections
#12
Karen Marie Juul Sørensen, Theresa Meldgaard, Connie Jenning Melchjorsen, Agla J Fridriksdottir, Henrik Pedersen, Ole William Petersen, Peter Kristensen
BACKGROUND: One of the hallmarks of cancer is an altered energy metabolism, and here, mitochondria play a central role. Previous studies have indicated that some mitochondrial ribosomal proteins change their expression patterns upon transformation. METHOD: In this study, we have used the selection of recombinant antibody libraries displayed on the surface of filamentous bacteriophage as a proteomics discovery tool for the identification of breast cancer biomarkers...
January 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28056744/nucleotide-second-messenger-signaling-as-a-target-for-the-control-of-bacterial-biofilm-formation
#13
Alberto J Martín-Rodríguez, Ute Römling
Bacterial biofilm formation and associated phenotypes are the major cause of chronic infection in humans. The major regulator of biofilm formation in Gram-negative and Gram-positive bacteria are nucleotide-based second messenger signaling pathways. Nucleotide-based signaling is a ubiquitous signal transduction mechanism in all domains of life that relay changes in the extracellular or intracellular milieu to protein or RNA effectors, leading to adaptive physiological responses. To date, six bona fide nucleotide signaling pathways, (p)ppGpp, cAMP, cGMP, c-di-AMP, c-di-GMP and cGAMP, have been characterized with respect to basic pathway modules and phenotypic and physiological output...
January 5, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28056160/discovery-of-a-potent-btk-inhibitor-with-a-novel-binding-mode-using-parallel-selections-with-a-dna-encoded-chemical-library
#14
John W Cuozzo, Paolo A Centrella, Diana Gikunju, Sevan Habeshian, Christopher D Hupp, Anthony D Keefe, Eric A Sigel, Holly H Soutter, Heather A Thomson, Ying Zhang, Matthew A Clark
We have identified and characterized novel potent inhibitors of Bruton's tyrosine kinase (BTK) from a single DNA encoded library of over 110 million compounds using multiple parallel selection conditions including variation in target concentration and addition of known binders to provide competition information. Distinct binding profiles were observed by comparing enrichments of library building-block combinations under these conditions; one enriched only at high concentrations of BTK and was competitive with ATP and another enriched at both high and low concentrations of BTK and was not competitive with ATP...
January 5, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28054243/differential-expression-and-mirna-regulation-of-the-gstp1-gene-in-the-regenerating-liver-of-chiloscyllium-plagiosum
#15
Yinghua Ge, Jiewen Zhang, Xinyi Shi, Conger Lu, Lingrong Yang, Yuanyuan Li, Yanna Chen, Dandan Cheng, Jing Bai, Zhengbing Lv, Lili Liu
Liver regeneration is a complicated process, and understanding the regulatory mechanism will be helpful in the treatment of diseases associated with liver. In this study, the one-third liver resection model was established in Chiloscyllium plagiosum, and the whole transcriptome of the C. plagiosum was generated using the Illumina-Solexa sequencing platform. Differentially expressed genes were analyzed using bioinformatics methods and verified using quantitative real-time PCR (qRT-PCR). Using miRanda and TargetScan, we screened the microRNA library for miRNAs that target the glutathione S-transferase P1(GSTP1) gene...
January 4, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28053164/the-papillomavirus-episteme-a-major-update-to-the-papillomavirus-sequence-database
#16
Koenraad Van Doorslaer, Zhiwen Li, Sandhya Xirasagar, Piet Maes, David Kaminsky, David Liou, Qiang Sun, Ramandeep Kaur, Yentram Huyen, Alison A McBride
The Papillomavirus Episteme (PaVE) is a database of curated papillomavirus genomic sequences, accompanied by web-based sequence analysis tools. This update describes the addition of major new features. The papillomavirus genomes within PaVE have been further annotated, and now includes the major spliced mRNA transcripts. Viral genes and transcripts can be visualized on both linear and circular genome browsers. Evolutionary relationships among PaVE reference protein sequences can be analysed using multiple sequence alignments and phylogenetic trees...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28049422/fast-gbs-a-new-pipeline-for-the-efficient-and-highly-accurate-calling-of-snps-from-genotyping-by-sequencing-data
#17
Davoud Torkamaneh, Jérôme Laroche, Maxime Bastien, Amina Abed, François Belzile
BACKGROUND: Next-generation sequencing (NGS) technologies have accelerated considerably the investigation into the composition of genomes and their functions. Genotyping-by-sequencing (GBS) is a genotyping approach that makes use of NGS to rapidly and economically scan a genome. It has been shown to allow the simultaneous discovery and genotyping of thousands to millions of SNPs across a wide range of species. For most users, the main challenge in GBS is the bioinformatics analysis of the large amount of sequence information derived from sequencing GBS libraries in view of calling alleles at SNP loci...
January 3, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28048283/we-h-204-03-part-2-history-and-archives-resources-at-aip-for-aapm-and-its-members
#18
M Mueller
: "William D. Coolidge, Inventor of the Modern X-ray Tube" David J. Allard, M.S., CHP - Director, PA DEP Bureau of Radiation Protection William David Coolidge 1873-1975 was a research scientist and inventor of the modern X-ray tube. Besides Roentgen, with his 1895 discovery and subsequent studies of X-rays, perhaps no other individual contributed more to the advancement of X-ray technology than did Coolidge. He was born in Hudson, MA and received his Bachelor of Science degree from MIT in 1896...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28047523/we-h-204-00-history-committee-symposium
#19
Michael Gossman
: "William D. Coolidge, Inventor of the Modern X-ray Tube" David J. Allard, M.S., CHP - Director, PA DEP Bureau of Radiation Protection William David Coolidge 1873-1975 was a research scientist and inventor of the modern X-ray tube. Besides Roentgen, with his 1895 discovery and subsequent studies of X-rays, perhaps no other individual contributed more to the advancement of X-ray technology than did Coolidge. He was born in Hudson, MA and received his Bachelor of Science degree from MIT in 1896...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28046866/we-h-204-01-william-d-coolidge-inventor-of-the-modern-x-ray-tube
#20
D Allard
: "William D. Coolidge, Inventor of the Modern X-ray Tube" David J. Allard, M.S., CHP - Director, PA DEP Bureau of Radiation Protection William David Coolidge 1873-1975 was a research scientist and inventor of the modern X-ray tube. Besides Roentgen, with his 1895 discovery and subsequent studies of X-rays, perhaps no other individual contributed more to the advancement of X-ray technology than did Coolidge. He was born in Hudson, MA and received his Bachelor of Science degree from MIT in 1896...
June 2016: Medical Physics
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