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https://www.readbyqxmd.com/read/29144750/investigation-of-the-physical-and-bioactive-properties-of-bromo-and-iodo-containing-sponge-derived-compounds-possessing-an-oxyphenylethanamine-core
#1
Erin P McCauley, Hanh Lam, Nicholas Lorig-Roach, Justin Luu, Cameron Lloyd, Karen Tenney, Halina Pietraszkiewicz, Cristina Diaz, Frederick A Valeriote, Victoria Auerbuch, Phillip Crews
This research set out to identify compounds from marine sponges that can act as bacterial virulence blockers. Extracts from a total of 80 sponges collected from throughout Indonesia were screened in a high-throughput NF-κB-based screen that identifies compounds capable of inhibiting the bacterial type III secretion system (T3SS) in Yersinia pseudotuberculosis. An extract that was shown to inhibit T3SS-driven NF-κB expression was obtained from an Iotrochota cf. iota sponge and was the source of seven new bromo- and iodo-containing compounds, all of which contain a 2-(4-oxyphenyl)ethan-1-amine core...
November 16, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/29144418/nmr-based-identification-of-metabolites-in-polar-and-non-polar-extracts-of-avian-liver
#2
Fariba Fathi, Antonio Brun, Katherine H Rott, Paulo Falco Cobra, Marco Tonelli, Hamid R Eghbalnia, Enrique Caviedes-Vidal, William H Karasov, John L Markley
Metabolites present in liver provide important clues regarding the physiological state of an organism. The aim of this work was to evaluate a protocol for high-throughput NMR-based analysis of polar and non-polar metabolites from a small quantity of liver tissue. We extracted the tissue with a methanol/chloroform/water mixture and isolated the polar metabolites from the methanol/water layer and the non-polar metabolites from the chloroform layer. Following drying, we re-solubilized the fractions for analysis with a 600 MHz NMR spectrometer equipped with a 1...
November 16, 2017: Metabolites
https://www.readbyqxmd.com/read/29144203/suppression-or-activation-of-immune-responses-by-predicted-secreted-proteins-of-the-soybean-rust-pathogen-phakopsora-pachyrhizi
#3
Mingsheng Qi, James P Grayczyk, Janina M Seitz, Youngsill Lee, Tobias I Link, Doil Choi, Kerry F Pedley, Ralf T Voegele, Thomas J Baum, Steven A Whitham
Rust fungi, such as the soybean rust pathogen Phakopsora pachyrhizi, are major threats to crop production. They form specialized haustoria that are hyphal structures intimately associated with host-plant cell membranes. These haustoria have roles in acquiring nutrients and secreting effector proteins that manipulate host immune systems. Functional characterization of effector proteins of rust fungi is important for understanding mechanisms that underlie their virulence and pathogenicity. Hundreds of candidate effector proteins have been predicted for rust pathogens, but it is not clear how to prioritize these effector candidates for further characterization...
November 16, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29143881/rmce-based-insect-cell-platform-to-produce-membrane-proteins-captured-on-hiv-1-gag-virus-like-particles
#4
João Vidigal, Bárbara Fernandes, Mafalda M Dias, Marco Patrone, António Roldão, Manuel J T Carrondo, Paula M Alves, Ana P Teixeira
Conformationally complex membrane proteins (MPs) are therapeutic targets in many diseases, but drug discovery has been slowed down by the lack of efficient production tools. Co-expression of MPs with matrix proteins from enveloped viruses is a promising approach to obtain correctly folded proteins at the surface of virus-like particles (VLPs), preserving their native lipidic environment. Here, we implemented a site-specific recombinase-mediated cassette exchange (RMCE) strategy to establish a reusable HIV-1 Gag-expressing insect cell line for fast production of target MPs on the surface of Gag-VLPs...
November 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29141209/high-throughput-drug-screening-identifies-pazopanib-and-clofilium-tosylate-as-promising-treatments-for-malignant-rhabdoid-tumors
#5
Céline Chauvin, Amaury Leruste, Arnault Tauziede-Espariat, Mamy Andrianteranagna, Didier Surdez, Aurianne Lescure, Zhi-Yan Han, Elodie Anthony, Wilfrid Richer, Sylvain Baulande, Mylène Bohec, Sakina Zaidi, Marie-Ming Aynaud, Laetitia Maillot, Julien Masliah-Planchon, Stefano Cairo, Sergio Roman-Roman, Olivier Delattre, Elaine Del Nery, Franck Bourdeaut
Rhabdoid tumors (RTs) are aggressive tumors of early childhood characterized by SMARCB1 inactivation. Their poor prognosis highlights an urgent need to develop new therapies. Here, we performed a high-throughput screening of approved drugs and identified broad inhibitors of tyrosine kinase receptors (RTKs), including pazopanib, and the potassium channel inhibitor clofilium tosylate (CfT), as SMARCB1-dependent candidates. Pazopanib targets were identified as PDGFRα/β and FGFR2, which were the most highly expressed RTKs in a set of primary tumors...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141039/identification-of-isolates-of-the-plant-pathogen-leptosphaeria-maculans-with-resistance-to-the-triazole-fungicide-fluquinconazole-using-a-novel-in-planta-assay
#6
Angela P Van de Wouw, Vicki L Elliott, Steven Chang, Francisco J López-Ruiz, Steven J Marcroft, Alexander Idnurm
Leptosphaeria maculans is the major pathogen of canola (oilseed rape, Brassica napus) worldwide. In Australia, the use of azole fungicides has contributed to the 50-fold increase in canola production in the last 25 years. However, extensive application of fungicides sets the stage for the selection of fungal populations with resistance. A high-throughput in planta assay was developed to allow screening of thousands of isolates from multiple populations. Using this screen, isolates were identified with decreased sensitivity to the fungicide fluquinconazole when applied at field rates as a protective seed dressing: these isolates cause significantly larger lesions on cotyledons and true leaves and increased disease severity at plant maturity...
2017: PloS One
https://www.readbyqxmd.com/read/29141026/in-depth-phenotypic-characterization-of-multicellular-tumor-spheroids-effects-of-5-fluorouracil
#7
Angélique Virgone-Carlotta, Manon Lemasson, Hichem C Mertani, Jean-Jacques Diaz, Sylvain Monnier, Thomas Dehoux, Hélène Delanoë-Ayari, Charlotte Rivière, Jean-Paul Rieu
MultiCellular Tumor Spheroids (MCTS), which mimic the 3-Dimensional (3D) organization of a tumor, are considered as better models than conventional cultures in 2-Dimensions (2D) to study cancer cell biology and to evaluate the response to chemotherapeutic drugs. A real time and quantitative follow-up of MCTS with simple and robust readouts to evaluate drug efficacy is still missing. Here, we evaluate the chemotherapeutic drug 5-Fluorouracil (5-FU) response on the growth and integrity of MCTS two days after treatment of MCTS and for three colorectal carcinoma cell lines with different cohesive properties (HT29, HCT116 and SW480)...
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
#8
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/29140426/development-and-validation-of-stereo-selective-method-for-the-separation-of-razoxane-enantiomers-in-hydrophilic-interaction-chromatography
#9
Ch Thirupathi, K Nagesh Kumar, G Srinivasu, Ch Lakshmi Narayana, Ch Parameswara Murthy
A novel sensitive and high throughput chiral hydrophilic interaction chromatographic (HILIC) method was developed to separate razoxane enantiomers namely levrazoxane (R-isomer) and dexrazoxane (DEX) in pharmaceutical active ingredient samples. A systematic chiral chromatographic screening system was employed in using multiple HPLC chromatographic modes on various polysaccharide based chiral columns to obtain a potential separation between enantiomers. HPLC separation was achieved using a mobile phase of aqueous 10 mM ammonium bicarbonate and mixture of organic modifiers (70/30, v/v) in the ratio of (5/95, v/v) on an immobilized polysaccharide based chiral stationary phase namely CHIRALPAK IE-3...
November 13, 2017: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/29139494/discovery-of-nicoyamycin-a-an-inhibitor-of-uropathogenic-escherichia-coli-growth-in-low-iron-environments
#10
Laura A Mike, Ashootosh Tripathi, Connor M Blankenship, Alyssa Saluk, Pamela J Schultz, Giselle Tamayo-Castillo, David H Sherman, Harry L T Mobley
High-throughput screening and activity-guided purification identified nicoyamycin A, a natural product comprised of an uncommon 3-methyl-1,4-dioxane ring incorporated into a desferrioxamine-like backbone via a spiroaminal linkage. Nicoyamycin A potently inhibits uropathogenic Escherichia coli growth in low iron medium, a promising step toward developing novel antibiotics to treat recalcitrant bacterial infections.
November 15, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29139199/in-silico-ligand-based-modeling-of-hbace-1-inhibitors
#11
Govindan Subramanian, Gennady Poda
Alzheimer's disease (AD) is a chronic neurodegenerative disease affecting more than 30 million people worldwide. Development of small molecule inhibitors of human β-secretase 1 (hBACE-1) is being the focus of pharmaceutical industry for the past 15-20 years. Here, we successfully applied multiple ligand-based in silico modeling techniques to understand the inhibitory activities of a diverse set of small molecule hBACE-1 inhibitors reported in the scientific literature. Strikingly, the use of only a small subset of 230 (13%) molecules allowed us to develop quality models that performed reasonably well on the validation set of 1476 (87%) inhibitors...
November 15, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29138487/associations-between-th17-related-inflammatory-cytokines-and-asthma-in-adults-a-case-control-study
#12
Ting Zhou, Xiji Huang, Yun Zhou, Jixuan Ma, Min Zhou, Yuewei Liu, Lili Xiao, Jing Yuan, Jungang Xie, Weihong Chen
Chronic airway inflammation is recognized as an essential process in the pathogenesis of asthma. Cytokine profiles derived from immune and inflammation cells such as T-helper (Th) cells, eosinophilia and neutrophilia are not limited to the Th2 type in asthma. However, little is understood about associations between Th2-low inflammatory cytokine profiles and risk of asthma in adults. A case-control study of 910 adult asthma and 881 healthy controls was conducted. Inflammatory cytokines screening was undertaken by high-throughput protein microarray technology, and Th17-related inflammatory cytokines (IL17A, IL-9, adipsin and CCL11) were finally selected...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138439/abma-a-small-molecule-that-inhibits-intracellular-toxins-and-pathogens-by-interfering-with-late-endosomal-compartments
#13
Yu Wu, Valérie Pons, Amélie Goudet, Laetitia Panigai, Annette Fischer, Jo-Ana Herweg, Sabrina Kali, Robert A Davey, Jérôme Laporte, Céline Bouclier, Rahima Yousfi, Céline Aubenque, Goulven Merer, Emilie Gobbo, Roman Lopez, Cynthia Gillet, Sandrine Cojean, Michel R Popoff, Pascal Clayette, Roger Le Grand, Claire Boulogne, Noël Tordo, Emmanuel Lemichez, Philippe M Loiseau, Thomas Rudel, Didier Sauvaire, Jean-Christophe Cintrat, Daniel Gillet, Julien Barbier
Intracellular pathogenic microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based high throughput screening for its capacity to protect human cells and mice against ricin toxin without toxicity...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138316/germline-cas9-expression-yields-highly-efficient-genome-engineering-in-a-major-worldwide-disease-vector-aedes-aegypti
#14
Ming Li, Michelle Bui, Ting Yang, Christian S Bowman, Bradley J White, Omar S Akbari
The development of CRISPR/Cas9 technologies has dramatically increased the accessibility and efficiency of genome editing in many organisms. In general, in vivo germline expression of Cas9 results in substantially higher activity than embryonic injection. However, no transgenic lines expressing Cas9 have been developed for the major mosquito disease vector Aedes aegypti Here, we describe the generation of multiple stable, transgenic Ae. aegypti strains expressing Cas9 in the germline, resulting in dramatic improvements in both the consistency and efficiency of genome modifications using CRISPR...
November 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29137939/in-silico-identification-and-in-vivo-characterization-of-small-molecule-therapeutic-hypothermia-mimetics
#15
Claire Coderch, María Díaz de Cerio, Jose María Zapico, Rafael Peláez, Ignacio M Larrayoz, Ana Ramos, Alfredo Martínez, Beatriz de Pascual-Teresa
Hypothermia has been proved to have a beneficial effect on several pathologies. CIRBP is one of the so termed cold-shock proteins involved in this process. In this work, we have detected small molecules capable of modulating the activity of CIRBP in the absence of a cold stimulus, by High Throughput Virtual Screening (HTVS) of the Diversity Set IV of the NCI and 15 compounds of our in-house data base. Fifteen compounds were selected from the HTVS to carry out a second screening through a cell-based Western blot assay...
October 31, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29137704/high-throughput-screening-of-phenoxy-carboxylic-acids-with-dispersive-solid-phase-extraction-followed-by-direct-analysis-in-real-time-mass-spectrometry
#16
Jiaqin Wang, Jun Zhu, Ling Si, Qi Du, Hongli Li, Wentao Bi, David Da Yong Chen
A high throughput, low environmental impact methodology for rapid determination of phenoxy carboxylic acids (PCAs) in water samples was developed by combing dispersive solid phase extraction (DSPE) using velvet-like graphitic carbon nitride (V-g-C3N4) and direct analysis in real time mass spectrometry (DART-MS). Due to the large surface area and good dispersity of V-g-C3N4, the DSPE of PCAs in water was completed within 20 s, and the elution of PCAs was accomplished in 20 s as well using methanol. The eluents were then analyzed and quantified using DART ionization source coupled to a high resolution mass spectrometer, where an internal standard was added in the samples...
December 15, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29137138/metabolic-profile-of-the-cellulolytic-industrial-actinomycete-thermobifida-fusca
#17
Niti Vanee, J Paul Brooks, Stephen S Fong
Actinomycetes have a long history of being the source of numerous valuable natural products and medicinals. To expedite product discovery and optimization of biochemical production, high-throughput technologies can now be used to screen the library of compounds present (or produced) at a given time in an organism. This not only facilitates chemical product screening, but also provides a comprehensive methodology to the study cellular metabolic networks to inform cellular engineering. Here, we present some of the first metabolomic data of the industrial cellulolytic actinomycete Thermobifida fusca generated using LC-MS/MS...
November 11, 2017: Metabolites
https://www.readbyqxmd.com/read/29136895/reactive-low-temperature-plasma-ionization-mass-spectrometry-for-the-determination-of-organic-uv-filters-in-personal-care-products
#18
Xuelu Ding, Stefanie Gerbig, Bernhard Spengler, Sabine Schulz
Organic UV filters in personal care products (PCPs) have been persistently reported as a potential threat to human health. In order to guarantee consumers(') safety, the dose of these compounds in PCPs needs to be monitored. Here, a methodology based on reactive low temperature plasma ionization (LTP) mass spectrometry (MS) has been developed for the determination of common organic UV filters in PCPs including benzophenone-3, ethylhexyl dimethyl p-aminobenzoic acid, ethylhexyl methoxycinnamate, 4-methylbenzylidene camphor, octocrylene, and ethylhexyl salicylate...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29134743/rapid-determination-of-ginkgolic-acids-in-ginkgo-biloba-kernels-and-leaves-by-direct-analysis-in-real-time-mass-spectrometry
#19
Zhongping Huang, Yueting Xu, Yilei Huang, Charles Liu, Kezhi Jiang, Lili Wang
A novel method on basis of direct analysis in real time integrated with mass spectrometry was established and applied into rapid determination of ginkgolic acids in Ginkgo biloba kernels and leaves. Instrument parameter settings were optimized to obtain the sensitive and accurate determination of ginkgolic acids. At the sample introduction speed of 0.2 mm/s, high intensity of [M-H](-) ions for ginkgolic acids were observed in the negative ion mode by utilization of high purity helium gas at 450°C. 2 μL methanol extract of Ginkgo biloba kernels or leaves dropped on the surface of Quick-Strip module was analyzed after solvent evaporated to dryness...
November 14, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/29134155/foliar-microbiome-transplants-confer-disease-resistance-in-a-critically-endangered-plant
#20
Geoffrey Zahn, Anthony S Amend
There has been very little effort to incorporate foliar microbiomes into plant conservation efforts even though foliar endophytes are critically important to the fitness and function of hosts. Many critically endangered plants that have been extirpated from the wild are dependent on regular fungicidal applications in greenhouses that cannot be maintained for remote out-planted populations, which quickly perish. These fungicides negatively impact potentially beneficial fungal symbionts, which may reduce plant defenses to pathogens once fungicide treatments are stopped...
2017: PeerJ
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