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Maria J Gonzalez-Moa, Bieke Van Dorst, Ole Lagatie, Ann Verheyen, Lieven Stuyver, Marco A Biamonte
Three O. volvulus immunogenic peptide sequences recently discovered by peptide microarray were adapted to a lateral flow assay (LFA). The LFA employs gold nanoshells as novel high-contrast reporter nanoparticles and detects a serological response against the 3 peptides, found in OvOC9384, OvOC198, and OvOC5528, respectively. When tested on 118 sera from O. volvulus infected patients and 208 control sera, the LFA was 90, 63, and 98% sensitive for each peptide, respectively, and 99-100% specific vs. samples from healthy volunteers...
March 16, 2018: ACS Infectious Diseases
Huijun Wang, Mark Fowler, David Messenge, Leon A Terry, Xuelan Gu, Luxian Zhou, Ruimin Liu, Juan Su, Songshan Shi, Jos Eacute Ordaz-Ortiz, Guoping Lian, Mark Berry, Shunchun Wang
Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41...
March 13, 2018: Journal of Agricultural and Food Chemistry
Lorenzo I Finci, Xiaofeng Zhang, Xiuliang Huang, Qiang Zhou, Jennifer Tsai, Teng Teng, Anant Agrawal, Betty Chan, Sean Irwin, Craig Karr, Andrew Cook, Ping Zhu, Dominic Reynolds, Peter G Smith, Peter Fekkes, Silvia Buonamici, Nicholas A Larsen
Somatic mutations in spliceosome proteins lead to dysregulated RNA splicing and are observed in a variety of cancers. These genetic aberrations may offer a potential intervention point for targeted therapeutics. SF3B1, part of the U2 small nuclear RNP (snRNP), is targeted by splicing modulators, including E7107, the first to enter clinical trials, and, more recently, H3B-8800. Modulating splicing represents a first-in-class opportunity in drug discovery, and elucidating the structural basis for the mode of action opens up new possibilities for structure-based drug design...
February 1, 2018: Genes & Development
Brigitte Le Magueresse-Battistoni, Luc Multigner, Claire Beausoleil, Christophe Rousselle
Based on rodent studies after prenatal and/or perinatal or adult exposure, there is now evidence that BPA may increase metabolic disturbances eventually leading to type-2 diabetes development via an ED MoA. In particular, BPA has been shown to alter insulin synthesis and/or release by pancreatic β-cells, and insulin signaling within insulin-sensitive organs (i.e., liver, muscle, adipose tissues). This resulted in variations in the expression of specific hepatic or adipose tissue markers, which are indicative of a state of insulin resistance...
February 23, 2018: Molecular and Cellular Endocrinology
Athina Liaskoni, Athina Angelopoulou, Efstathia Voulgari, Maria-Teodora Popescu, Constantinos Tsitsilianis, Konstantinos Avgoustakis
Paclitaxel (PTX)-loaded gold nanoparticles functionalized with mercaptooctanoic acid (MOA) and folic acid (FA) (AuMOA-FA) were encapsulated within pH-sensitive poly(2-vinylpyridine)-b-poly(ethylene oxide) (P2VP-PEO) vesicles with the aim to develop a more selective injectable nano-formulation for PTX, lacking the side effects of the conventional PTX delivery system. The size of the resulting composite vesicles was lower than 200 nm, i.e. it is suitable for tumor targeting applications taking advantage of the enhanced permeability and retention (EPR) effect...
February 22, 2018: European Journal of Pharmaceutical Sciences
Nikolai L Chepelev, Rémi Gagné, Timothy Maynor, Byron Kuo, Cheryl A Hobbs, Leslie Recio, Carole L Yauk
Acrylamide (AA) exposure causes increased incidence of forestomach, lung, and Harderian gland tumors in male mice. One hypothesized mode of action (MOA) for AA-carcinogenicity includes genotoxicity/mutagenicity as a key event, possibly resulting from AA metabolism to the direct genotoxic metabolite glycidamide. Alternatively, altered calcium signaling (CS) has been proposed as a central key event in the MOA. To examine the plausibility of these proposed MOAs, RNA-sequencing was performed on tumor target tissues: Harderian glands (the most sensitive tumor target tissue in the rodent 2-year cancer bioassay) and lungs of AA-exposed male CD-1 mice...
February 20, 2018: Regulatory Toxicology and Pharmacology: RTP
Mattia Zampieri, Balazs Szappanos, Maria Virginia Buchieri, Andrej Trauner, Ilaria Piazza, Paola Picotti, Sébastien Gagneux, Sonia Borrell, Brigitte Gicquel, Joel Lelievre, Balazs Papp, Uwe Sauer
Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets...
February 21, 2018: Science Translational Medicine
Emily G Armitage, Amjed Q I Alqaisi, Joanna Godzien, Imanol Peña, Alison J Mbekeani, Vanesa Alsonso-Herranz, Ángeles López-Gonzálvez, Julio Martín, Raquel Gabarro, Paul W Denny, Michael P Barrett, Coral Barbas
With the World Health Organization reporting over 30,000 deaths and 200-400,000 new cases annually, visceral Leishmania sis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for Leishmania sis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new, more successful treatments for Leishmania sis...
February 20, 2018: Antimicrobial Agents and Chemotherapy
Li Xie, Tânia Gomes, Knut Asbjørn Solhaug, You Song, Knut Erik Tollefsen
Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers...
February 10, 2018: Aquatic Toxicology
Mattias Bood, Sangamesh Sarangamath, Moa S Wranne, Morten Grøtli, L Marcus Wilhelmsson
Förster resonance energy transfer (FRET) between a donor nucleobase analogue and an acceptor nucleobase analogue, base-base FRET, works as a spectroscopic ruler and protractor. With their firm stacking and ability to replace the natural nucleic acid bases inside the base-stack, base analogue donor and acceptor molecules complement external fluorophores like the Cy-, Alexa- and ATTO-dyes and enable detailed investigations of structure and dynamics of nucleic acid containing systems. The first base-base FRET pair, tCO-tCnitro, has recently been complemented with among others the adenine analogue FRET pair, qAN1-qAnitro, increasing the flexibility of the methodology...
2018: Beilstein Journal of Organic Chemistry
Kevin D Lafferty, Skylar R Hopkins
No abstract text is available yet for this article.
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Alexander P Boast, Laura S Weyrich, Jamie R Wood, Jessica L Metcalf, Rob Knight, Alan Cooper
Over the past 50,000 y, biotic extinctions and declines have left a legacy of vacant niches and broken ecological interactions across global terrestrial ecosystems. Reconstructing the natural, unmodified ecosystems that preceded these events relies on high-resolution analyses of paleoecological deposits. Coprolites are a source of uniquely detailed information about trophic interactions and the behaviors, gut parasite communities, and microbiotas of prehistoric animal species. Such insights are critical for understanding the legacy effects of extinctions on ecosystems, and can help guide contemporary conservation and ecosystem restoration efforts...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Thomas Prod'homme, Scott S Zamvil
Glatiramer acetate (GA) is a synthetic amino acid copolymer that is approved for treatment of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS). GA reduces multiple sclerosis (MS) disease activity and has shown comparable efficacy with high-dose interferon-β. The mechanism of action (MOA) of GA has long been an enigma. Originally, it was recognized that GA treatment promoted expansion of GA-reactive T-helper 2 and regulatory T cells, and induced the release of neurotrophic factors...
February 12, 2018: Cold Spring Harbor Perspectives in Medicine
Karin Jensen, Moa Pontén
No abstract text is available yet for this article.
February 12, 2018: Läkartidningen
Tânia Gomes, You Song, Dag A Brede, Li Xie, Kristine B Gutzkow, Brit Salbu, Knut Erik Tollefsen
Among aquatic organisms, invertebrate species such as the freshwater crustacean Daphnia magna are believed to be sensitive to gamma radiation, although information on responses at the individual, biochemical and molecular level is scarce. Following gamma radiation exposure, biological effects are attributed to the formation of free radicals, formation of reactive oxygen species (ROS) and subsequently oxidative damage to lipids, proteins and DNA in exposed organisms. Thus, in the present study, effects and modes of action (MoA) have been investigated in D...
February 9, 2018: Science of the Total Environment
Martha M Moore, Rita S Schoeny, Richard A Becker, Kimberly White, Lynn H Pottenger
Adverse outcome pathways (AOPs) are frameworks starting with a molecular initiating event (MIE), followed by key events (KEs) linked by KE relationships (KERs), ultimately resulting in a specific adverse outcome. Relevant data for the pathway and each KE/KER are evaluated to assess biological plausibility, weight-of-evidence, and confidence. We aimed to describe an AOP relevant to chemicals directly inducing mutation in cancer critical gene(s), via the formation of chemical-specific pro-mutagenic DNA adduct(s), as an early critical step in tumor etiology...
February 12, 2018: Critical Reviews in Toxicology
Ethan J Anderson, Jimmy T Efird, Andy C Kiser, Patricia B Crane, Wesley T O'Neal, T Bruce Ferguson, Hazaim Alwair, Kendal Carter, J Mark Williams, Anil K Gehi, Alan P Kypson
OBJECTIVES: This study sought to determine whether plasma catecholamines and monoamine oxidase-B (MOA-B) are associated with post-operative atrial fibrillation (POAF) in patients undergoing elective cardiac surgery. BACKGROUND: Although intra- and post-operative adrenergic tone has been demonstrated to be an causative factor for POAF, the role and association of pre-operative plasma catecholamines remains unclear. METHODS: Prior to administration of anesthesia on the morning of surgery, blood samples were obtained from 324 patients undergoing nonemergent coronary artery bypass graft and/or aortic valve surgery with cardiopulmonary bypass at East Carolina Heart Institute...
December 11, 2017: JACC. Clinical Electrophysiology
Luana de Morais E Silva, Mateus Feitosa Alves, Luciana Scotti, Wilton Silva Lopes, Marcus Tullius Scotti
Persistent organic products are compounds used for various purposes, such as personal care products, surfactants, colorants, industrial additives, food, pesticides and pharmaceuticals. These substances are constantly introduced into the environment and many of these pollutants are difficult to degrade. Toxic compounds classified as MoA 1 (Mode of Action 1) are low toxicity compounds that comprise nonreactive chemicals. In silico methods such as Quantitative Structure-Activity Relationships (QSARs) have been used to develop important models for prediction in several areas of science, as well as aquatic toxicity studies...
February 7, 2018: Ecotoxicology and Environmental Safety
Ning Zhang, Martin Zoltner, Ka-Fai Leung, Paul Scullion, Sebastian Hutchinson, Ricardo C Del Pino, Isabel M Vincent, Yong-Kang Zhang, Yvonne R Freund, Michael R K Alley, Robert T Jacobs, Kevin D Read, Michael P Barrett, David Horn, Mark C Field
Recent development of benzoxaborole-based chemistry gave rise to a collection of compounds with great potential in targeting diverse infectious diseases, including human African Trypanosomiasis (HAT), a devastating neglected tropical disease. However, further medicinal development is largely restricted by a lack of insight into mechanism of action (MoA) in pathogenic kinetoplastids. We adopted a multidisciplinary approach, combining a high-throughput forward genetic screen with functional group focused chemical biological, structural biology and biochemical analyses, to tackle the complex MoAs of benzoxaboroles in Trypanosoma brucei...
February 9, 2018: PLoS Pathogens
Zichen Wang, Alexander Lachmann, Alexandra B Keenan, Avi Ma'ayan, Oliver Stegle
Motivation: As part of the NIH Library of Integrated Network-based Cellular Signatures (LINCS) program, hundreds of thousands of transcriptomic signatures were generated with the L1000 technology, profiling the response of human cell lines to over 20,000 small molecule compounds. This effort is a promising approach toward revealing the mechanisms-of-action (MOA) for marketed drugs and other less studied potential therapeutic compounds. Results: L1000 fireworks display (L1000FWD) is a web application that provides interactive visualization of over 16,000 drug and small-molecule induced gene expression signatures...
February 6, 2018: Bioinformatics
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