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https://www.readbyqxmd.com/read/28346741/small-molecules-targeting-human-n-acetylmannosamine-kinase
#1
Stephan Hinderlich, Martin Neuenschwander, Paul-Robin Wratil, Andreas Oder, Michael Lisurek, Long D Nguyen, Jens Peter von Kries, Christian Hackenberger
N-Acetylmannosamine kinase (MNK) plays a key role in the biosynthesis of sialic acids and glycosylation of proteins. Sialylated glycoconjugates affect a large number of biological processes, including immune modulation and cancer transformation. For the search of effective inhibitors of MNK we applied high-throughput screening of drug-like small molecules. Applying different orthogonal assays for their validation we identified four potential MNK-specific inhibitors with IC50 values in the low micromolar range...
March 27, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28346094/drug-library-screening-for-the-identification-of-ionophores-that-correct-the-mistrafficking-disorder-associated-with-oxalosis-kidney-disease
#2
Shurong Hou, Franck Madoux, Louis Scampavia, Jo Ann Janovick, P Michael Conn, Timothy P Spicer
Primary hyperoxaluria is the underlying cause of oxalosis and is a life-threatening autosomal recessive disease, for which treatment may require dialysis or dual liver-kidney transplantation. The most common primary hyperoxaluria type 1 (PH1) is caused by genetic mutations of a liver-specific enzyme alanine:glyoxylate aminotransferase (AGT), which results in the misrouting of AGT from the peroxisomes to the mitochondria. Pharmacoperones are small molecules with the ability to modify misfolded proteins and route them correctly within the cells, which may present an effective strategy to treat AGT misrouting in PH1 disorders...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346087/pubchem-bioassay
#3
Yanli Wang, Tiejun Cheng, Stephen H Bryant
High-throughput screening (HTS) is now routinely conducted for drug discovery by both pharmaceutical companies and screening centers at academic institutions and universities. Rapid advance in assay development, robot automation, and computer technology has led to the generation of terabytes of data in screening laboratories. Despite the technology development toward HTS productivity, fewer efforts were devoted to HTS data integration and sharing. As a result, the huge amount of HTS data was rarely made available to the public...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28344750/the-effectiveness-of-policy-interventions-for-school-bullying-a-systematic-review
#4
William Hall
OBJECTIVE: Bullying threatens the mental and educational well-being of students. Although anti-bullying policies are prevalent, little is known about their effectiveness. This systematic review evaluates the methodological characteristics and summarizes substantive findings of studies examining the effectiveness of school bullying policies. METHOD: Searches of 11 bibliographic databases yielded 489 studies completed since January 1, 1995. Following duplicate removal and double-independent screening based on a priori inclusion criteria, 21 studies were included for review...
2017: Journal of the Society for Social Work and Research
https://www.readbyqxmd.com/read/28344082/circ-znf609-is-a-circular-rna-that-can-be-translated-and-functions-in-myogenesis
#5
Ivano Legnini, Gaia Di Timoteo, Francesca Rossi, Mariangela Morlando, Francesca Briganti, Olga Sthandier, Alessandro Fatica, Tiziana Santini, Adrian Andronache, Mark Wade, Pietro Laneve, Nikolaus Rajewsky, Irene Bozzoni
Circular RNAs (circRNAs) constitute a family of transcripts with unique structures and still largely unknown functions. Their biogenesis, which proceeds via a back-splicing reaction, is fairly well characterized, whereas their role in the modulation of physiologically relevant processes is still unclear. Here we performed expression profiling of circRNAs during in vitro differentiation of murine and human myoblasts, and we identified conserved species regulated in myogenesis and altered in Duchenne muscular dystrophy...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28343242/identification-of-a-polysaccharide-produced-by-the-pyruvate-overproducer-candida-glabrata-cctcc-m202019
#6
Zhengshan Luo, Song Liu, Guocheng Du, Jingwen Zhou, Jian Chen
Candida glabrata has great potential for the accumulation of pyruvate as a preferred strain in pyruvate production by fermentation. However, its substrate conversion rate is relatively low. In this study, a novel polysaccharide containing α-1,4-glucosidic bonds was observed accidentally in screening a high-titer pyruvate strain by atmospheric and room temperature plasma mutagenesis of C. glabrata. Chemical analysis of the partially purified polysaccharide S4-C10 showed the main components were 1.2% (w/w) protein and 94...
March 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28340202/validity-and-reproducibility-of-the-start-back-tool-dutch-version-in-patients-with-low-back-pain-in-primary-care-settings
#7
Jasper D Bier, Raymond W J G Ostelo, Miranda L van Hooff, Bart W Koes, Arianne P Verhagen
Objective: To translate, and to investigate the reliability and validity of the STarT Back screening tool (SBT) in the primary care setting among patients with non-specific low back pain (LBP). Methods: The SBT was formally translated in Dutch following a multistep approach for forward and backward translation. General practitioners and physiotherapists included patients with LBP. Patients completed a baseline a questionnaire and a follow-up at three days and three months...
March 9, 2017: Physical Therapy
https://www.readbyqxmd.com/read/28338311/validation-of-self-confidence-scale-for-clean-urinary-intermittent-self-catheterization-for-patients-and-health-caregivers
#8
Cintia Fernandes Baccarin Biaziolo, Alessandra Mazzo, José Carlos Amado Martins, Beatriz Maria Jorge, Rui Carlos Negrão Batista, Silvio Júnior Tucci
OBJECTIVE: To validate a measurement instrument for clean intermittent self-catheterization for patients and health-caregivers. MATERIAL AND METHODS: Methodological study of instrument validation performed at a Rehabilitation Center in a University hospital for patients submitted to clean intermittent self-catheterization and their health-caregivers. Following ethical criteria, data were collected during interview with nurse staff using a Likert question form containing 16 items with 5 points each: "no confidence"=1, "little confidence"=2, "confident"=3, "very confident"=4 and "completely confident"=5...
March 24, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28336360/gain-a-graph-based-method-to-automatically-analyze-neurite-outgrowth-in-cell-cultures
#9
B L Long, H Li, A Mahadevan, T Tang, K Balotin, N Grandel, J Soto, S Y Wong, A Abrego, S Li, A A Qutub
BACKGROUND: Neurite outgrowth is a metric widely used to assess the success of in vitro neural stem cell differentiation or neuron reprogramming protocols and of high-content screening assays for neural regenerative drug discovery. However, neurite measurements are tedious to perform manually, and there is a paucity of freely available, fully automated software to determine neurite measurements and neuron counting. To provide such a tool to the neurobiology, stem cell, cell engineering, and neuroregenerative communities, we developed an algorithm for performing high-throughput neurite analysis in immunofluorescence images...
March 20, 2017: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/28335513/bioactive-potential-of-marine-macroalgae-from-the-central-red-sea-saudi-arabia-assessed-by-high-throughput-imaging-based-phenotypic-profiling
#10
Stephan Kremb, Constanze Müller, Philippe Schmitt-Kopplin, Christian R Voolstra
Marine algae represent an important source of novel natural products. While their bioactive potential has been studied to some extent, limited information is available on marine algae from the Red Sea. This study aimed at the broad discovery of new bioactivities from a collection of twelve macroalgal species from the Central Red Sea. We used imaging-based High-Content Screening (HCS) with a diverse spectrum of cellular markers for detailed cytological profiling of fractionated algal extracts. The cytological profiles for 3 out of 60 algal fractions clustered closely to reference inhibitors and showed strong inhibitory activities on the HIV-1 reverse transcriptase in a single-enzyme biochemical assay, validating the suggested biological target...
March 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28333254/comparison-of-efficacy-and-complications-among-various-spacer-grafts-in-the-treatment-of-lower-eyelid-retraction-a-systematic-review
#11
Eugene Park, Kevin Lewis, Mohammed S Alghoul
Background: Lower eyelid retraction is a difficult problem to treat, but it is a prevalent condition and a common complication of blepharoplasty. The use of spacer grafts to increase eyelid height and improve symptoms has been described for a long time, but the optimal choice of spacer graft material is unknown. Objectives: The authors reviewed the currently available evidence to determine the best available spacer graft material in terms of efficacy and complications...
March 3, 2017: Aesthetic Surgery Journal
https://www.readbyqxmd.com/read/28332413/interlaboratory-validation-of-an-lc-ms-ms-method-for-the-determination-of-melamine-and-cyanuric-acid-in-animal-feed
#12
Hildburg Fry, Kerstin Mietle, Eileen Mähnert, Sebastian Zinke, Mandy Schwieters, Emanuele Pydde, Angelika Preiß-Weigert
Melamine and cyanuric acid have been mixed illegally into food and feed to increase the nitrogen content which results in deceptively high protein contents. As a consequence a maximum level for melamine of 2.5 mg kg(-1) feed was established by the European Union under directive 2002/32/EC. A method is required to quantify melamine and cyanuric acid for control of the maximum level. Therefore Technical Committee (TC) 327 of the European Committee for Standardisation (CEN) commissioned the standardisation of a method for the analysis of melamine and cyanuric acid in animal feed...
March 23, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/28328318/toward-discovery-of-novel-microtubule-targeting-agents-a-snap-tag-based-high-content-screening-assay-for-the-analysis-of-microtubule-dynamics-and-cell-cycle-progression
#13
Nina Berges, Katharina Arens, Verena Kreusch, Rainer Fischer, Stefano Di Fiore
Microtubule targeting agents (MTAs) are used for the treatment of cancer. Novel MTAs could provide additional and beneficial therapeutic options. To improve the sensitivity and throughput of standard immunofluorescence assays for the characterization of MTAs, we used SNAP-tag technology to produce recombinant tubulin monomers. To visualize microtubule filaments, A549 cells transfected with SNAP-tubulin were stained with a membrane-permeable, SNAP-reactive dye. The treatment of SNAP-tubulin cells with stabilizing MTAs such as paclitaxel resulted in the formation of coarsely structured microtubule filaments, whereas depolymerizing MTAs such as nocodazole resulted in diffuse staining patterns in which the tubulin filaments were no longer distinguishable...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28328144/diagnosing-and-preventing-iron-overload
#14
Ganesh Ramanathan, John K Olynyk, Paolo Ferrari
Absolute or functional iron (Fe) deficiency is an important determinant of anemia in hemodialysis patients and parenteral Fe is routinely used to treat this condition in conjunction with erythropoiesis stimulating agents. While restoration of hemoglobin toward the target range is a good outcome of Fe replacement, it is well known that Fe overload and toxicity may be adverse consequences of this therapy. Dialysis clinical practice guidelines recommend tailoring Fe therapy based on transferrin saturation and serum ferritin levels...
March 22, 2017: Hemodialysis International
https://www.readbyqxmd.com/read/28327127/effects-of-vitellaria-paradoxa-c-f-gaertn-aqueous-leaf-extract-administration-on-salmonella-typhimurium-infected-rats
#15
Siméon Pierre Chegaing Fodouop, Sedric Donald Tala, Lunga Paul Keilah, Norbert Kodjio, Mefokou Didiane Yemele, Armel Herve Kamdje Nwabo, Bridget Nji-Kah, Joseph Tchoumboue, Donatien Gatsing
BACKGROUND: The present study investigates the effects of Vitellaria paradoxa crude extract administration on Salmonella typhimurium infected Wistar rats. METHODS: Rats were infected by single dose oral administration of Salmonella typhimurium (1.5×10(8) CFU). Negative control groups were infected and treated orally with distilled water (vehicle), neutral control group were not infected, while the four test groups were treated up to 18 days with 55 mg/kg, 110 mg/kg, 220 mg/kg and 440 mg/kg body weight of aqueous extract of V...
March 21, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28322504/rapid-characterization-of-the-major-chemical-constituents-from-polygoni-multiflori-caulis-by-liquid-chromatography-tandem-mass-spectrometry-and-comparative-analysis-with-polygoni-multiflori-radix
#16
Gui-Yang Wang, Jing Shang, Yun Wu, Gang Ding, Wei Xiao
Polygoni Multiflori Caulis is a traditional Chinese medicine that has been used for a long time to treat sleep disorders. However, the multiple chemical composition analysis has not been reported. In this study, a simple, rapid and effective ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was established to characterize the components of Polygoni Multiflori Caulis. In addition, a chemical comparative analysis was performed with Polygoni Multiflori Radix, another traditional Chinese medicine from the same plant, through multivariate statistical analysis and semi-quantitative analysis to screen the difference in chemical ingredients between these two herbal medicines from same medicinal plant...
March 21, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/28320982/comparison-of-three-acute-stress-models-for-simulating-the-pathophysiology-of-stress-related-mucosal-disease
#17
Bhagawati Saxena, Sanjay Singh
Stress-related mucosal disease (SRMD) is highly prevalent in intensive care patients leading to increasing treatment cost and mortality. SRMD is a disease elusive of ideal treatment. Evaluation of drugs is very pertinent for the efficient and safe treatment of SRMD. It relies mainly on in vivo screening models. There are various stress models, and till date, none of them is validated for simulating the SRMD pathophysiology. The present study aims to choose the best model, which reproduce pathophysiology of SRMD, among previously established stress models...
March 19, 2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28320616/high-content-screen-using-zebrafish-danio-rerio-embryos-identifies-a-novel-kinase-activator-and-inhibitor
#18
Werner J Geldenhuys, Sadie A Bergeron, Jackie E Mullins, Rowaa Aljammal, Briah L Gaasch, Wei-Chi Chen, June Yun, Lori A Hazlehurst
In this report we utilized zebrafish (Danio rerio) embryos in a phenotypical high-content screen (HCS) to identify novel leads in a cancer drug discovery program. We initially validated our HCS model using the flavin adenosine dinucleotide (FAD) containing endoplasmic reticulum (ER) enzyme, endoplasmic reticulum oxidoreductase (ERO1) inhibitor EN460. EN460 showed a dose response effect on the embryos with a dose of 10μM being significantly lethal during early embryonic development. The HCS campaign which employed a small library identified a promising lead compound, a naphthyl-benzoic acid derivative coined compound 1 which had significant dosage and temporally dependent effects on notochord and muscle development in zebrafish embryos...
February 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28303654/live-cell-imaging-of-bacterial-cells-pyrenoylpyrrole-based-fluorescence-labelling
#19
Arun Divakar Mathiyazhagan, Sivakumar Shanmugam
A novel substituted pyrenoylpyrroles was synthesized by the reaction of pyrenoyl chalcone, TosMIC and methyl iodide under mild condition. All the synthesized compounds were screened for their bioactivity and the MIC was determined, among which few compounds showed moderate antibacterial activity towards gram-positive as well as negative bacteria. Further, cytotoxicity assay ascertained that these compounds were non-toxic to mammalian cells as well. The pyrene chromophore in the synthesized compounds (3a-e) and (5a-e) is responsible for the good photophysical properties which have an absorbance at λ 340 nm and emission at λ 410 nm...
March 17, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28303392/lettuce-flavonoids-screening-and-phenotyping-by-chlorophyll-fluorescence-excitation-ratio
#20
Marek Zivcak, Klaudia Brückova, Oksana Sytar, Marian Brestic, Katarina Olsovska, Suleyman I Allakhverdiev
Environmentally induced variation and the genotypic differences in flavonoid and phenolic content in lettuce can be reliably detected using the appropriate parameters derived from the records of rapid non-invasive fluorescence technique. The chlorophyll fluorescence excitation ratio method was designed as a rapid and non-invasive tool to estimate the content of UV-absorbing phenolic compounds in plants. Using this technique, we have assessed the dynamics of accumulation of flavonoids related to developmental changes and environmental effects...
March 16, 2017: Planta
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