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https://www.readbyqxmd.com/read/28346107/a-high-throughput-method-for-measuring-drug-residence-time-using-the-transcreener-adp-assay
#1
Meera Kumar, Robert G Lowery
Analysis of drug-target residence times during drug development can result in improved efficacy, increased therapeutic window, and reduced side effects. Residence time can be estimated as the reciprocal of the dissociation rate ( koff) of an inhibitor from its target. The traditional methods for measuring koff require synthesis of labeled ligands or low-throughput label-free methods. To provide an alternative that is better suited to an automated high-throughput screening (HTS) environment, we adapted a classic "jump dilution" catalytic assay method for determination of koff values for kinase inhibitor drugs...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28343997/dna-double-strand-breaks-and-aurora-b-mislocalization-induced-by-exposure-of-early-mitotic-cells-to-h2o2-appear-to-increase-chromatin-bridges-and-resultant-cytokinesis-failure
#2
Min-Guk Cho, Ju-Hyun Ahn, Hee-Song Choi, Jae-Ho Lee
Aneuploidy, an abnormal number of chromosomes that is a hallmark of cancer cells, can arise from tetraploid/binucleated cells through a failure of cytokinesis. Reactive oxygen species (ROS) have been implicated in various diseases, including cancer. However, the nature and role of ROS in cytokinesis progression and related mechanisms has not been clearly elucidated. Here, using time-lapse analysis of asynchronously growing cells and immunocytochemical analyses of synchronized cells, we found that hydrogen peroxide (H2O2) treatment at early mitosis (primarily prometaphase) significantly induced cytokinesis failure...
March 24, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28343969/pds5-regulates-sister-chromatid-cohesion-and-chromosome-bi-orientation-through-a-conserved-protein-interaction-module
#3
Yuhei Goto, Yuya Yamagishi, Miyuki Shintomi-Kawamura, Mayumi Abe, Yuji Tanno, Yoshinori Watanabe
Sister-chromatid cohesion is established by the cohesin complex in S phase and persists until metaphase, when sister chromatids are captured by microtubules emanating from opposite poles [1]. The Aurora-B-containing chromosome passenger complex (CPC) plays a crucial role in achieving chromosome bi-orientation by correcting erroneous microtubule attachment [2]. The centromeric localization of the CPC relies largely on histone H3-T3 phosphorylation (H3-pT3), which is mediated by the mitotic histone kinase Haspin/Hrk1 [3-5]...
March 18, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28342286/switching-aurora-a-kinase-on-and-off-at-an-allosteric-site
#4
REVIEW
Richard Bayliss, Selena G Burgess, Patrick J McIntyre
Protein kinases are central players in the regulation of cell cycle and signalling pathways. Their catalytic activities are strictly regulated through post-translational modifications and protein-protein interactions that control switching between inactive and active states. These states have been studied extensively using protein crystallography, although the dynamic nature of protein kinases makes it difficult to capture all relevant states. Here we describe two recent structures of Aurora-A kinase that trap its active and inactive states...
March 25, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28340462/assessment-of-arsenic-and-fluorine-in-surface-soil-to-determine-environmental-and-health-risk-factors-in-the-comarca-lagunera-mexico
#5
Yareli A Sariñana-Ruiz, Jorge Vazquez-Arenas, Fabiola S Sosa-Rodríguez, Israel Labastida, Ma Aurora Armienta, Antonio Aragón-Piña, Miguel A Escobedo-Bretado, Laura S González-Valdez, Patricia Ponce-Peña, Hugo Ramírez-Aldaba, René H Lara
Total, bioaccessible and mobile concentrations of arsenic and fluorine are determined in polluted surface soil within the Comarca Lagunera region using standardized protocols to obtain a full description of the environmental behavior for these elements. The composition of mineral phases associated with them is evaluated with microscopic and spectroscopic techniques. Mineralogical characterizations indicate that ultra-fine particles (<1-5 μm) including mimetite-vanadite (Pb5(AsO4)3Cl, Pb5(AsO4, VO4)3Cl)-like, lead arseniate (Pb3(AsO4)2)-like and complex arsenic-bearing compounds are main arsenic-bearing phases, while fluorite (CaF2) is the only fluorine-bearing phase...
March 10, 2017: Chemosphere
https://www.readbyqxmd.com/read/28340400/pharmacoinformatics-exploration-of-polyphenol-oxidases-leading-to-novel-inhibitors-by-virtual-screening-and-molecular-dynamic-simulation-study
#6
Mubashir Hassan, Qamar Abbas, Zaman Ashraf, Ahmed A Moustafa, Sung-Yum Seo
Polyphenol oxidases (PPOs)/tyrosinases are metal-dependent enzymes and known as important targets for melanogenesis. Although considerable attempts have been conducted to control the melanin-associated diseases by using various inhibitors. However, the exploration of the best anti-melanin inhibitor without side effect still remains a challenge in drug discovery. In present study, protein structure prediction, ligand-based pharmacophore modeling, virtual screening, molecular docking and dynamic simulation study were used to screen the strong novel inhibitor to cure melanogenesis...
March 15, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28337805/defining-the-anti-cancer-activity-of-tricarbonyl-rhenium-complexes-induction-of-g2-m-cell-cycle-arrest-and-blockade-of-aurora-a-kinase-phosphorylation
#7
Peter V Simpson, Ilaria Casari, Silvano Paternoster, Brian W Skelton, Marco Falasca, Massimiliano Massi
Rhenium and ruthenium complexes containing N-heterocylic carbene (NHC) ligands and conjugated to indomethacin were prepared. The anticancer properties were probed against pancreatic cell lines, revealing a remarkable activity of the rhenium fragment as anticancer agent. The ruthenium complexes were found to be inactive against the same pancreatic cancer cell lines, either alone or in conjugation with indomethacin. An in depth biological study revealed the origin of the anticancer properties of the rhenium tricarbonyl fragment, of which a complete elucidation had yet to be achieved...
March 23, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28335548/study-of-different-variants-of-mo-enzyme-crarc-and-the-interaction-with-its-partners-crcytb5-r-and-crcytb5-1
#8
Alejandro Chamizo-Ampudia, Aurora Galvan, Emilio Fernandez, Angel Llamas
The mARC (mitochondrial Amidoxime Reducing Component) proteins are recently discovered molybdenum (Mo) Cofactor containing enzymes. They are involved in the reduction of several N-hydroxylated compounds (NHC) and nitrite. Some NHC are prodrugs containing an amidoxime structure or mutagens such as 6-hydroxylaminopurine (HAP). We have studied this protein in the green alga Chlamydomonas reinhardtii (crARC). Interestingly, all the ARC proteins need the reducing power supplied by other proteins. It is known that crARC requires a cytochrome b₅ (crCytb5-1) and a cytochrome b₅ reductase (crCytb5-R) that form an electron transport chain from NADH to the substrates...
March 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28328870/the-effect-of-early-life-experience-environment-and-genetic-factors-on-spontaneous-home-cage-aggression-related-wounding-in-male-c57bl-6-mice
#9
Brianna N Gaskill, Aurora M Stottler, Joseph P Garner, Christina W Winnicker, Guy B Mulder, Kathleen R Pritchett-Corning
Aggression is a major welfare issue in mice, particularly when mice unfamiliar to each other are first placed in cages, as happens on receipt from a vendor, and following cage cleaning. Injuries from aggression are the second leading cause of unplanned euthanasia in mice, following ulcerative dermatitis. Commonly employed strategies for reducing aggression-related injury are largely anecdotal, and may even be counterproductive. Here we report a series of experiments testing potential explanations and interventions for post-shipping aggression-related injuries in C57BL/6 mice...
March 22, 2017: Lab Animal
https://www.readbyqxmd.com/read/28326231/in-situ-monitoring-by-raman-spectroscopy-of-the-thermal-doping-of-graphene-and-mos2-in-o2-controlled-atmosphere
#10
Aurora Piazza, Filippo Giannazzo, Gianpiero Buscarino, Gabriele Fisichella, Antonino La Magna, Fabrizio Roccaforte, Marco Cannas, Franco Mario Gelardi, Simonpietro Agnello
The effects of temperature and atmosphere (air and O2) on the doping of monolayers of graphene (Gr) on SiO2 and Si substrates, and on the doping of MoS2 multilayer flakes transferred on the same substrates have been investigated. The investigations were carried out by in situ micro-Raman spectroscopy during thermal treatments up to 430 °C, and by atomic force microscopy (AFM). The spectral positions of the G and 2D Raman bands of Gr undergo only minor changes during treatment, while their amplitude and full width at half maximum (FWHM) vary as a function of the temperature and the used atmosphere...
2017: Beilstein Journal of Nanotechnology
https://www.readbyqxmd.com/read/28325394/can-mindfulness-based-interventions-improve-the-quality-of-life-of-patients-with-moderate-severe-alopecia-areata-a-prospective-pilot-study
#11
Rosella Gallo, Carlo Chiorri, Giulia Gasparini, Alessio Signori, Anna Burroni, Aurora Parodi
No abstract text is available yet for this article.
April 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28323327/an-explicit-model-for-the-inbreeding-load-in-the-evolutionary-analysis-of-selfing
#12
Aurora García-Dorado
I present analytical predictions for the equilibrium inbreeding load expected in a population under mutation, selection and a regular mating system, for any population size and for any magnitude and recessivity of the deleterious effects. Using this prediction, I deduce the relative fitness of mutant alleles with small effect on selfing, to explore the situations where selfing or outcrossing are expected to evolve. The results obtained are in agreement with previous literature, showing that natural selection is expected to lead to stable equilibria where populations show either complete outcrossing or complete selfing, and that selfing is promoted by large deleterious mutation rates...
March 21, 2017: Evolution; International Journal of Organic Evolution
https://www.readbyqxmd.com/read/28322787/aurka-promotes-cancer-metastasis-by-regulating-epithelial-mesenchymal-transition-and-cancer-stem-cell-properties-in-hepatocellular-carcinoma
#13
Chenlin Chen, Guangyuan Song, Jue Xiang, Hongcheng Zhang, Shaoyun Zhao, Yinchu Zhan
AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development; however, its role and underlying mechanisms in the metastasis of hepatocellular carcinoma (HCC) remain unknown. In this study, We found that AURKA was up-regulated in HCC tissues and correlated with pathological stage and distant metastasis. Further found that AURKA was involved in the cancer metastases after radiation in HCC. While overexpression of AURKA induced epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) behaviors though PI3K/AKT pathway, silencing AURKA suppressed radiation-enhanced cell invasiveness of HCC...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28320082/rosmarinic-acid-plays-a-protective-role-in-the-embryogenesis-of-zebrafish-exposed-to-food-colours-through-its-influence-on-aurora-kinase-a-level
#14
Y Swarnalatha, I S Jerrine Joseph, Tippabathani Jayakrishna
OBJECTIVE: To evaluate the protective nature of the rosmarinic acid from Sphaeranthus amaranthoides during zebra fish embryogenesis. METHODS: Rosmarinic acid was isolated from the S. amaranthoides. An accurate, sensitive and simple LC-MS analysis was performed to determine the rosmarinic acid from S. amaranthoides. In the present study, zebrafish embryos were exposed to crimson red and sunset yellow at a concentration of 0.1 and 0.5mg/l and the effect of these food colours on the levels of aurora kinase A was studied individually...
March 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#15
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28319064/oct4-controls-mitotic-stability-and-inactivates-the-rb-tumor-suppressor-pathway-to-enhance-ovarian-cancer-aggressiveness
#16
E Comisso, M Scarola, M Rosso, S Piazza, S Marzinotto, Y Ciani, M Orsaria, L Mariuzzi, C Schneider, S Schoeftner, R Benetti
OCT4 (Octamer-binding transcription factor 4) is essential for embryonic stem cell self-renewal. Here we show that OCT4 increases the aggressiveness of high-grade serous ovarian cancer (HG-SOC) by inactivating the Retinoblastoma tumor suppressor pathway and enhancing mitotic stability in cancer cells. OCT4 drives the expression of Nuclear Inhibitor of Protein Phosphatase type 1 (NIPP1) and Cyclin F (CCNF) that together inhibit Protein Phosphatase 1 (PP1). This results in pRB hyper-phosphorylation, accelerated cell proliferation and increased in vitro tumorigenicity of ovarian cancer cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28317883/optical-determination-of-shockley-read-hall-and-interface-recombination-currents-in-hybrid-perovskites
#17
Valerio Sarritzu, Nicola Sestu, Daniela Marongiu, Xueqing Chang, Sofia Masi, Aurora Rizzo, Silvia Colella, Francesco Quochi, Michele Saba, Andrea Mura, Giovanni Bongiovanni
Metal-halide perovskite solar cells rival the best inorganic solar cells in power conversion efficiency, providing the outlook for efficient, cheap devices. In order for the technology to mature and approach the ideal Shockley-Queissier efficiency, experimental tools are needed to diagnose what processes limit performances, beyond simply measuring electrical characteristics often affected by parasitic effects and difficult to interpret. Here we study the microscopic origin of recombination currents causing photoconversion losses with an all-optical technique, measuring the electron-hole free energy as a function of the exciting light intensity...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315405/location-and-functional-analysis-of-the-aspergillus-nidulans-aurora-kinase-confirm-mitotic-functions-and-suggest-non-mitotic-roles
#18
Colin P De Souza, Shahr B Hashmi, Natalie Hage, Rebecca M Fitch, Aysha H Osmani, Stephen A Osmani
Filamentous fungi have devastating negative impacts as pathogens and agents of food spoilage but also have critical ecological importance and are utilized for industrial applications. The characteristic multinucleate nature of filamentous fungi is facilitated by limiting if, when and where septation, the fungal equivalent of cytokinesis, occurs. In the model filamentous fungus Aspergillus nidulans septation does not occur immediately after mitosis and is an incomplete process resulting in the formation of a septal pore whose permeability is cell cycle regulated...
March 14, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28314741/an-engineered-minimal-chromosomal-passenger-complex-reveals-a-role-for-incenp-sli15-spindle-association-in-chromosome-biorientation
#19
Sarah Fink, Kira Turnbull, Arshad Desai, Christopher S Campbell
The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore-microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define the minimal CPC elements essential for its biorientation function. We engineered a minimal CPC comprised of the dimerized last third of the kinase-activating Sli15/INCENP scaffold and the catalytic subunit Ipl1/Aurora B...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28314740/dual-recognition-of-chromatin-and-microtubules-by-incenp-is-important-for-mitotic-progression
#20
Michael S Wheelock, David J Wynne, Boo Shan Tseng, Hironori Funabiki
The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain...
March 17, 2017: Journal of Cell Biology
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