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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29793206/effects-on-the-hepatic-transcriptome-of-chicken-embryos-in-ovo-exposed-to-phenobarbital
#2
Jiahua Guo, Shohei Ito, Hoa Thanh Nguyen, Kimika Yamamoto, Hisato Iwata
This work aimed at evaluating the toxic effects of in ovo exposure to phenobarbital (PB) and unveiling the mode of action by transcriptome analysis in the embryonic liver of a model avian species, chicken (Gallus gallus). Embryos were initially treated with saline or 1 μg PB /g egg at Hamburger Hamilton Stage (HHS) 1 (1st day), followed by 20 days of incubation to HHS 46. At 21st day, chicks that pipped successfully were euthanized and dissected for assessing the PB caused effects on phenotypes and the liver transcriptome in both genders...
May 21, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29793175/apolipoprotein-ciii-and-n-terminal-prohormone-b-type-natriuretic-peptide-as-independent-predictors-for-cardiovascular-disease-in-type-2-diabetes
#3
Marco Colombo, Helen C Looker, Bassam Farran, Felix Agakov, M Julia Brosnan, Paul Welsh, Naveed Sattar, Shona Livingstone, Paul N Durrington, D John Betteridge, Paul M McKeigue, Helen M Colhoun
BACKGROUND AND AIMS: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. METHODS: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo...
May 21, 2018: Atherosclerosis
https://www.readbyqxmd.com/read/29793106/microplastics-in-mussels-sampled-from-coastal-waters-and-supermarkets-in-the-united-kingdom
#4
Jiana Li, Christopher Green, Alan Reynolds, Huahong Shi, Jeanette M Rotchell
Global contamination of the marine environment by plastic has led to the discovery of microplastics in a range of marine species, including those for human consumption. In this study, the presence of microplastics and other anthropogenic debris in seawater and mussels (Mytilus edulis) from coastal waters of the U.K., as well as supermarket sources, was investigated. These were detected in all samples from all sites with spatial differences observed. Seawater samples taken from 6 locations (in triplicates) displayed 3...
May 21, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29793072/leveraging-semantic-labels-for-multi-level-abstraction-in-medical-process-mining-and-trace-comparison
#5
Giorgio Leonardi, Manuel Striani, Silvana Quaglini, Anna Cavallini, Stefania Montani
Many medical information systems record data about the executed process instances in the form of an event log. In this paper, we present a framework, able to convert actions in the event log into higher level concepts, at different levels of abstraction, on the basis of domain knowledge. Abstracted traces are then provided as an input to trace comparison and semantic process discovery. Our abstraction mechanism is able to manage non trivial situations, such as interleaved actions or delays between two actions that abstract to the same concept...
May 21, 2018: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/29793032/phosphorylated-and-non-phosphorylated-hck-kinase-domains-produced-by-cell-free-protein-expression
#6
Kazushige Katsura, Yuri Tomabechi, Takayoshi Matsuda, Mayumi Yonemochi, Junko Mikuni, Noboru Ohsawa, Takaho Terada, Shigeyuki Yokoyama, Mutsuko Kukimoto-Niino, Chie Takemoto, Mikako Shirouzu
Since phosphorylation is involved in various physiological events, kinases and interacting factors can be potential targets for drug discovery. For the development and improvement of inhibitors from the point of view of mechanistic enzymology, a cell-free protein synthesis system would be advantageous, since it could prepare mutant proteins easily. However, especially in the case of protein kinase, product solubility remains one of the major challenges. To overcome this problem, we prepared a chaperone-supplemented extract from Escherichia coli BL21 cells harboring a plasmid encoding a set of chaperone genes, dnaK, dnaJ, and grpE...
May 21, 2018: Protein Expression and Purification
https://www.readbyqxmd.com/read/29792883/plasma-n-glycan-signatures-associate-with-features-of-inflammatory-bowel-diseases
#7
Florent Clerc, Mislav Novokmet, Viktoria Dotz, Karli R Reiding, Noortje de Haan, Guinevere S M Kammeijer, Hans Dalebout, Marco R Bladergroen, Frano Vukovic, Erdmann Rapp, Stephan R Targan, Gildardo Barron, Natalia Manetti, Anna Latiano, Dermot P B McGovern, Vito Annese, Gordan Lauc, Manfred Wuhrer
BACKGROUND & AIMS: Biomarkers are needed for early detection of Crohn's disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex post-translational modification of proteins that affects their structure and activity. We compared plasma N-glycosylation profiles between patients with CD or UC and healthy individuals (controls). METHODS: We analyzed the total plasma N-glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique...
May 21, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29792858/luciferase-of-the-japanese-syllid-polychaete-odontosyllis-umdecimdonta
#8
Darrin T Schultz, Alexey A Kotlobay, Rustam Ziganshin, Artyom Bannikov, Nadezhda M Markina, Tatiana V Chepurnyh, Ekaterina S Shakhova, Ksenia Palkina, Steven H D Haddock, Ilia V Yampolsky, Yuichi Oba
Odontosyllis undecimdonta is a marine syllid polychaete that produces bright internal and exuded bioluminescence. Despite over fifty years of biochemical investigation into Odontosyllis bioluminescence, the light-emitting small molecule substrate and catalyzing luciferase protein have remained a mystery. Here we describe the discovery of a bioluminescent protein fraction from O. undecimdonta, the identification of the luciferase using peptide and RNA sequencing, and the in vitro reconstruction of the bioluminescence reaction using highly purified O...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792805/a-cheminformatic-insight-into-the-differences-between-terrestrial-and-marine-originated-natural-products
#9
Jun Shang, Ben Hu, Junmei Wang, Feng Zhu, Yu Kang, Dan Li, Huiyong Sun, De-Xin Kong, Tingjun Hou
This is a new golden age for the drug discovery based on natural products derived from both marine and terrestrial sources. Herein, a straightforward but important question is what are the major structural differences between marine natural products (MNPs) and terrestrial natural products (TNPs). To answer this question, we analyzed the important physicochemical properties, structural features and drug-likeness of the two types of natural products and discussed their differences from the perceptive of evolution...
May 24, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29792758/investigation-of-a-large-scale-gopher-tortoise-gopherus-polyphemus-mortality-event-on-a-public-conservation-land-in-florida
#10
Michelina C Dziadzio, Eric R Sievers, Deborah Burr
In August 2015, a gopher tortoise ( Gopherus polyphemus) mortality event was documented on a 40-ha area of Lake Louisa State Park, Lake County, Florida, USA. To quantify the extent of the die-off and the seroprevalence of Mycoplasma agassizii and Mycoplasma testudineum, two causative agents of mycoplasmal upper respiratory tract disease (URTD), we conducted a tortoise shell survey on 25 and 26 August 2015 and collected blood samples from live tortoises on 2-4 September 2015 and 1-13 August 2016 within the area of documented mortality...
May 24, 2018: Journal of Wildlife Diseases
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#11
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792712/targeted-discovery-and-combinatorial-biosynthesis-of-polycyclic-tetramate-macrolactam-combamides-a-e
#12
Yan Liu, Haoxin Wang, Rentai Song, Jining Chen, Tianhong Li, Yaoyao Li, Liangcheng Du, Yuemao Shen
Polycyclic tetramate macrolactams (PoTeMs) are a growing class of natural products with distinct structure and diverse biological activities. By promoter engineering and heterologous expression of the cryptic cbm gene cluster, four new PoTeMs, combamides A-E (1-4), were identified. Additionally, two new derivatives, combamides E (5) and F (6), were generated via combinatorial biosynthesis. Together, our findings provide a sound base for expanding the structure diversities of PoTeMs through genome mining and combinatorial biosynthesis...
May 24, 2018: Organic Letters
https://www.readbyqxmd.com/read/29792705/total-synthesis-of-boletopsin-11-enabled-by-directed-ortho-c-sp-2-h-arylation
#13
Meng Yao Zhang, Russell A Barrow
A nine-step synthesis of boletopsin 11 (1), a bioactive fungal natural product, is disclosed. Key features include a one-pot [O]-oxa-Michael cascade to establish the polyoxygenated dibenzofuran core followed by a Pd-catalyzed directed ortho-C(sp2 )-H arylation to complete the fully functionalized carbon skeleton. Exploration of the latter transformation led to the discovery of an unexpected tandem ortho-C(sp2 )-H arylation event, and the scope of the directed ortho-C(sp2 )-H reaction was further investigated with coupling partners varying in stereoelectronic properties...
May 24, 2018: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29792526/phages-antibiotic-resistance-are-the-most-abundant-entities-on-earth-ready-for-a-comeback
#14
Colin Hill, Susan Mills, Reynolds P Ross
Bacteriophages, which lost out to antibiotic therapy in the past, may be poised to make a comeback. Once discarded because of their narrow activity spectrum, it can now be viewed as a major advantage that these intracellular, self-replicating entities can exert their killing effect with minimal damage to the commensal microbiome. In eastern Europe, phages continue to be used both prophylactically and therapeutically to treat infections. More recently, much needed regulated clinical trials are underway with a view to restoring phage therapy as a tool for mainstream medicine, although current regulations may impede their full potential...
May 24, 2018: Future Microbiology
https://www.readbyqxmd.com/read/29792459/teamwork-in-healthcare-key-discoveries-enabling-safer-high-quality-care
#15
Michael A Rosen, Deborah DiazGranados, Aaron S Dietz, Lauren E Benishek, David Thompson, Peter J Pronovost, Sallie J Weaver
Few industries match the scale of health care. In the United States alone, an estimated 85% of the population has at least 1 health care encounter annually and at least one quarter of these people experience 4 to 9 encounters annually. A single visit requires collaboration among a multidisciplinary group of clinicians, administrative staff, patients, and their loved ones. Multiple visits often occur across different clinicians working in different organizations. Ineffective care coordination and the underlying suboptimal teamwork processes are a public health issue...
May 2018: American Psychologist
https://www.readbyqxmd.com/read/29792456/teamwork-situated-in-multiteam-systems-key-lessons-learned-and-future-opportunities
#16
Marissa L Shuffler, Dorothy R Carter
Many important contexts requiring teamwork, including health care, space exploration, national defense, and scientific discovery, present important challenges that cannot be addressed by a single team working independently. Instead, the complex goals these contexts present often require effectively coordinated efforts of multiple specialized teams working together as a multiteam system (MTS). For almost 2 decades, researchers have endeavored to understand the novelties and nuances for teamwork and collaboration that ensue when teams operate together as "component teams" in these interdependent systems...
May 2018: American Psychologist
https://www.readbyqxmd.com/read/29792453/team-composition-and-the-abcs-of-teamwork
#17
Suzanne T Bell, Shanique G Brown, Anthony Colaneri, Neal Outland
In teams, some combinations of people work together better than others. A large body of literature with a rich history suggests that the configuration of team member attributes, called team composition, has a fundamental influence on teamwork. Team composition shapes the emergence of affective states, behavioral processes, and cognitive states (the ABCs of teamwork), which ultimately affect how teams meet their objectives. The purpose of this article is to describe what is known about team composition and its influence on the ABCs of teamwork...
May 2018: American Psychologist
https://www.readbyqxmd.com/read/29792391/role-of-neutrophils-in-equine-asthma
#18
Benjamin Uberti, Gabriel Morán
Neutrophilic bronchiolitis is the primary lesion in asthma-affected horses. Neutrophils are key actors in host defense, migrating toward sites of inflammation and infection, where they act as early responder cells toward external insults. However, neutrophils can also mediate tissue damage in various non-infectious inflammatory processes. Within the airways, these cells likely contribute to bronchoconstriction, mucus hypersecretion, and pulmonary remodeling by releasing pro-inflammatory mediators, including the cytokines interleukin (IL)-8 and IL-17, neutrophil elastase, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs)...
May 24, 2018: Animal Health Research Reviews
https://www.readbyqxmd.com/read/29792354/challenges-with-biomarkers-in-cancer-drug-discovery-and-development
#19
Ecaterina Ileana Dumbrava, Funda Meric-Bernstam, Timothy A Yap
No abstract text is available yet for this article.
May 24, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29792329/residual-complexity-does-impact-organic-chemistry-and-drug-discovery-the-case-of-rufomyazine-and-rufomycin
#20
Mary P Choules, Larry L Klein, David C Lankin, James B McAlpine, Sang-Hyun Cho, Jinhua Cheng, Hanki Lee, Joo-Won Suh, Birgit U Jaki, Scott G Franzblau, Guido F Pauli
Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13 C (1...
May 24, 2018: Journal of Organic Chemistry
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