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https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#1
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342443/test-retest-reliability-of-transcranial-magnetic-stimulation-eeg-evoked-potentials
#2
Lewis J Kerwin, Corey J Keller, Wei Wu, Manjari Narayan, Amit Etkin
BACKGROUND: Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs), recorded using electroencephalography (TMS-EEG), offer a powerful tool for measuring causal interactions in the human brain. However, the test-retest reliability of TEPs, critical to their use in clinical biomarker and interventional studies, remains poorly understood. OBJECTIVE/HYPOTHESIS: We quantified TEP reliability to: (i) determine the minimal TEP amplitude change which significantly exceeds that associated with simply re-testing, (ii) locate the most reliable scalp regions of interest (ROIs) and TEP peaks, and (iii) determine the minimal number of TEP pulses for achieving reliability...
December 29, 2017: Brain Stimulation
https://www.readbyqxmd.com/read/29342431/comparison-of-access-type-on-perioperative-outcomes-after-endovascular-aortic-aneurysm-repair
#3
Jeffrey J Siracuse, Alik Farber, Jeffrey A Kalish, Douglas W Jones, Denis Rybin, Gheorghe Doros, Salvatore T Scali, Marc L Schermerhorn
OBJECTIVE: Endovascular aneurysm repair (EVAR) can be performed through percutaneous or surgical access. Our goal was to assess the difference in perioperative outcomes based on access type in a real-world setting. METHODS: The Vascular Quality Initiative (VQI) database was queried for EVAR. Univariable analysis and multivariable analysis were used to determine the independent effect of access type. RESULTS: There were 8340 (64%) and 4747 (36%) EVAR procedures performed through percutaneous and surgical access (3395 [72%] transverse and 1352 [28%] vertical incisions)...
January 13, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29342400/a-unifying-framework-of-synaptic-and-intrinsic-plasticity-in-neural-populations
#4
Johannes Leugering, Gordon Pipa
A neuronal population is a computational unit that receives a multivariate, time-varying input signal and creates a related multivariate output. These neural signals are modeled as stochastic processes that transmit information in real time, subject to stochastic noise. In a stationary environment, where the input signals can be characterized by constant statistical properties, the systematic relationship between its input and output processes determines the computation carried out by a population. When these statistical characteristics unexpectedly change, the population needs to adapt to its new environment if it is to maintain stable operation...
January 17, 2018: Neural Computation
https://www.readbyqxmd.com/read/29342354/a-highly-dynamic-loop-of-the-pseudomonas-aeruginosa-pa14-type-iv-pilin-is-essential-for-pilus-assembly
#5
Ylan Nguyen, Stephen Boulton, E Tyler McNicholl, Madoka Akimoto, Hanjeong Harvey, Francisca Aidoo, Giuseppe Melacini, Lori L Burrows
Type IVa pili (T4aP) are long, thin surface filaments involved in attachment, motility, biofilm formation, and DNA uptake. They are important virulence factors for many bacteria, including Pseudomonas aeruginosa, an opportunistic pathogen and common cause of hospital-acquired infections. Each helical filament contains thousands of monomers of the major pilin subunit, PilA. Each P. aeruginosa strain expresses one of five phylogenetically distinct major pilins, which vary in sequence and the nature of their associated accessory protein(s)...
January 17, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29342276/a-predictive-quantitative-model-of-spiking-activity-and-stimulus-secretion-coupling-in-oxytocin-neurons
#6
Jorge Maícas-Royo, Gareth Leng, Duncan J MacGregor
Oxytocin neurons of the rat hypothalamus project to the posterior pituitary where they secrete their products into the bloodstream. The pattern and quantity of that release depends on the afferent inputs to the neurons, on their intrinsic membrane properties, and on non-linear interactions between spiking activity and exocytosis: a given number of spikes will trigger more secretion when they arrive close together. Here we present a quantitative computational model of oxytocin neurons that can replicate the results of a wide variety of published experiments...
January 12, 2018: Endocrinology
https://www.readbyqxmd.com/read/29342271/melodi-mining-enriched-literature-objects-to-derive-intermediates
#7
Benjamin Elsworth, Karen Dawe, Emma E Vincent, Ryan Langdon, Brigid M Lynch, Richard M Martin, Caroline Relton, Julian P T Higgins, Tom R Gaunt
Background: The scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis. Methods: Here we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts...
January 12, 2018: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29342260/interaction-between-staphylococcus-aureus-and-pseudomonas-aeruginosa-is-beneficial-for-colonisation-and-pathogenicity-in-a-mixed-biofilm
#8
Patrícia M Alves, Eide Al-Badi, Cathryn Withycombe, Paul M Jones, Kevin J Purdy, Sarah E Maddocks
Debate regarding the co-existence of Staphylococcus aureus and Pseudomonas aeruginosa in wounds remains contentious, with the dominant hypothesis describing a situation akin to niche partitioning, whereby both microorganisms are present but occupy distinct regions of the wound without interacting. In contrast, we hypothesised that these microorganisms do interact during early co-colonisation in a manner beneficial to both bacteria. We assessed competitive interaction between S. aureus and P. aeruginosa in biofilm cultured for 24-72 h and bacterial aggregates analogous to those observed in early ( < 24h) biofilm formation, and interaction with human keratinocytes...
January 12, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29342258/insulin-and-estrogen-independently-and-differentially-reduce-macronutrient-intake-in-healthy-men
#9
Rosemarie Krug, Linda Mohwinkel, Bernhard Drotleff, Jan Born, Manfred Hallschmid
Context: Insulin administration to the central nervous system inhibits food intake, but this effect has been found to be less pronounced in female compared to male organisms. This sex-specific pattern has been suggested to arise from a modulating influence of estrogen signaling on the insulin effect. Objective: We assessed in healthy young men whether pre-treatment with transdermal estradiol interacts with the hypophagic effect of central nervous insulin administration via the intranasal pathway...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29342229/a-rapid-epistatic-mixed-model-association-analysis-by-linear-retransformations-of-genomic-estimated-values
#10
Chao Ning, Dan Wang, Huimin Kang, Raphael Mrode, Lei Zhou, Shizhong Xu, Jian-Feng Liu
Motivation: Epistasis provides a feasible way for probing potential genetic mechanism of complex traits. However, time-consuming computation challenges successful detection of interaction in practice, especially when linear mixed model (LMM) is used to control type I error in the presence of population structure and cryptic relatedness. Results: A rapid epistatic mixed-model association analysis (REMMA) method was developed to overcome computational limitation. This method first estimates individuals' epistatic effects by an extended genomic best linear unbiased prediction (EG-BLUP) model with additive and epistatic kinship matrix, then pairwise interaction effects are obtained by linear retransformations of individuals' epistatic effects...
January 12, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29342221/genotype-by-environment-interactions-affecting-heterosis-in-maize
#11
Zhi Li, Lisa Coffey, Jacob Garfin, Nathan D Miller, Michael R White, Edgar P Spalding, Natalia de Leon, Shawn M Kaeppler, Patrick S Schnable, Nathan M Springer, Candice N Hirsch
The environment can influence heterosis, the phenomena in which the offspring of two inbred parents exhibits phenotypic performance beyond the inbred parents for specific traits. In this study we measured 25 traits in a set of 47 maize hybrids and their inbred parents grown in 16 different environments with varying levels of average productivity. By quantifying 25 vegetative and reproductive traits across the life cycle we were able to analyze interactions between the environment and multiple distinct instances of heterosis...
2018: PloS One
https://www.readbyqxmd.com/read/29342212/sequence-variation-in-plasmodium-falciparum-merozoite-surface-protein-2-is-associated-with-virulence-causing-severe-and-cerebral-malaria
#12
Suwanna Chaorattanakawee, Pornlada Nuchnoi, Hathairad Hananantachai, Uranan Tumkosit, David Saunders, Izumi Naka, Jun Ohashi, Jintana Patarapotikul
Parasite virulence, an important factor contributing to the severity of Plasmodium falciparum infection, varies among P. falciparum strains. Relatively little is known regarding markers of virulence capable of identifying strains responsible for severe malaria. We investigated the effects of genetic variations in the P.f. merozoite surface protein 2 gene (msp2) on virulence, as it was previously postulated as a factor. We analyzed 300 msp2 sequences of single P. falciparum clone infection from patients with uncomplicated disease as well as those admitted for severe malaria with and without cerebral disease...
2018: PloS One
https://www.readbyqxmd.com/read/29342194/tolerance-to-mild-salinity-stress-in-japonica-rice-a-genome-wide-association-mapping-study-highlights-calcium-signaling-and-metabolism-genes
#13
Julien Frouin, Antoine Languillaume, Justine Mas, Delphine Mieulet, Arnaud Boisnard, Axel Labeyrie, Mathilde Bettembourg, Charlotte Bureau, Eve Lorenzini, Muriel Portefaix, Patricia Turquay, Aurore Vernet, Christophe Périn, Nourollah Ahmadi, Brigitte Courtois
Salinity tolerance is an important quality for European rice grown in river deltas. We evaluated the salinity tolerance of a panel of 235 temperate japonica rice accessions genotyped with 30,000 SNP markers. The panel was exposed to mild salt stress (50 mM NaCl; conductivity of 6 dS m-1) at the seedling stage. Eight different root and shoot growth parameters were measured for both the control and stressed treatments. The Na+ and K+ mass fractions of the stressed plants were measured using atomic absorption spectroscopy...
2018: PloS One
https://www.readbyqxmd.com/read/29342177/a-new-fluorescent-dye-accumulation-assay-for-parallel-measurements-of-the-abcg2-abcb1-and-abcc1-multidrug-transporter-functions
#14
Edit Szabó, Dóra Türk, Ágnes Telbisz, Nóra Kucsma, Tamás Horváth, Gergely Szakács, László Homolya, Balázs Sarkadi, György Várady
ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. In this study we have examined the potential interactions of three key human ABC multidrug transporters with PhenGreen diacetate (PGD), a cell permeable fluorescent metal ion indicator. The non-fluorescent, hydrophobic PGD rapidly enters the cells and, after cleavage by cellular esterases, in the absence of quenching metal ions, PhenGreen (PG) becomes highly fluorescent...
2018: PloS One
https://www.readbyqxmd.com/read/29342175/immunocontraceptive-target-repertoire-defined-by-systematic-identification-of-sperm-membrane-alloantigens-in-a-single-species
#15
Nathaly Cormier, John J McGlone, John Leszyk, Daniel M Hardy
Sperm competence in animal fertilization requires the collective activities of numerous sperm-specific proteins that are typically alloimmunogenic in females. Consequently, sperm membrane alloantigens are potential targets for contraceptives that act by blocking the proteins' functions in gamete interactions. Here we used a targeted proteomics approach to identify the major alloantigens in swine sperm membranes and lipid rafts, and thereby systematically defined the repertoire of these sperm-specific proteins in a single species...
2018: PloS One
https://www.readbyqxmd.com/read/29342169/interactions-between-the-invasive-burmese-python-python-bivittatus-kuhl-and-the-local-mosquito-community-in-florida-usa
#16
Lawrence E Reeves, Kenneth L Krysko, Michael L Avery, Jennifer L Gillett-Kaufman, Akito Y Kawahara, C Roxanne Connelly, Phillip E Kaufman
The Burmese python, Python bivittatus Kuhl, is a well-established invasive species in the greater Everglades ecosystem of southern Florida, USA. Most research on its ecological impacts focuses on its role as a predator and its trophic interactions with native vertebrate species, particularly mammals. Beyond predation, there is little known about the ecological interactions between P. bivittatus and native faunal communities. It is likely that established populations of P. bivittatus in southern Florida serve as hosts for native mosquito communities...
2018: PloS One
https://www.readbyqxmd.com/read/29342159/prediction-of-novel-target-genes-and-pathways-involved-in-bevacizumab-resistant-colorectal-cancer
#17
Precious Takondwa Makondi, Chia-Hwa Lee, Chien-Yu Huang, Chi-Ming Chu, Yu-Jia Chang, Po-Li Wei
Bevacizumab combined with cytotoxic chemotherapy is the backbone of metastatic colorectal cancer (mCRC) therapy; however, its treatment efficacy is hampered by therapeutic resistance. Therefore, understanding the mechanisms underlying bevacizumab resistance is crucial to increasing the therapeutic efficacy of bevacizumab. The Gene Expression Omnibus (GEO) database (dataset, GSE86525) was used to identify the key genes and pathways involved in bevacizumab-resistant mCRC. The GEO2R web tool was used to identify differentially expressed genes (DEGs)...
2018: PloS One
https://www.readbyqxmd.com/read/29342158/real-time-community-detection-in-full-social-networks-on-a-laptop
#18
Benjamin Paul Chamberlain, Josh Levy-Kramer, Clive Humby, Marc Peter Deisenroth
For a broad range of research and practical applications it is important to understand the allegiances, communities and structure of key players in society. One promising direction towards extracting this information is to exploit the rich relational data in digital social networks (the social graph). As global social networks (e.g., Facebook and Twitter) are very large, most approaches make use of distributed computing systems for this purpose. Distributing graph processing requires solving many difficult engineering problems, which has lead some researchers to look at single-machine solutions that are faster and easier to maintain...
2018: PloS One
https://www.readbyqxmd.com/read/29342152/do-nursery-habitats-provide-shelter-from-flow-for-juvenile-fish
#19
Darren M Parsons, Iain MacDonald, Dane Buckthought, Crispin Middleton
Juvenile fish nurseries are an essential life stage requirement for the maintenance of many fish populations. With many inshore habitats globally in decline, optimising habitat management by increasing our understanding of the relationship between juvenile fish and nursery habitats may be a prudent approach. Previous research on post-settlement snapper (Chrysophrys auratus) has suggested that structure may provide a water flow refuge, allowing snapper to access high water flow sites that will also have a high flux of their pelagic prey...
2018: PloS One
https://www.readbyqxmd.com/read/29342146/a-theory-of-how-active-behavior-stabilises-neural-activity-neural-gain-modulation-by-closed-loop-environmental-feedback
#20
Christopher L Buckley, Taro Toyoizumi
During active behaviours like running, swimming, whisking or sniffing, motor actions shape sensory input and sensory percepts guide future motor commands. Ongoing cycles of sensory and motor processing constitute a closed-loop feedback system which is central to motor control and, it has been argued, for perceptual processes. This closed-loop feedback is mediated by brainwide neural circuits but how the presence of feedback signals impacts on the dynamics and function of neurons is not well understood. Here we present a simple theory suggesting that closed-loop feedback between the brain/body/environment can modulate neural gain and, consequently, change endogenous neural fluctuations and responses to sensory input...
January 17, 2018: PLoS Computational Biology
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