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51.
Mark Andrews Alan Brown Jean-Yves Chiva David Fradet David Gordon Mark Lansdell Malcolm MacKenny 《Bioorganic & medicinal chemistry letters》2009,19(8):2329-2332
The reported selective serotonin Re-uptake Inhibitor Litoxetine was used as the starting point in the design of a range of potential SSRIs with high ease of synthetic accessibility. Preparation and subsequent optimization yielded a range of potent and highly selective SSRIs. 相似文献
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Marta Bassitta Joana M. Buades Ana Pérez-Cembranos Valentín Pérez-Mellado Barbara Terrasa Richard P. Brown Pilar Navarro Javier Lluch Jesús Ortega Jose A. Castro Antònia Picornell Cori Ramon 《Zoologica scripta》2020,49(6):668-683
The phylogenetic relationships among the wall lizards of the Podarcis hispanicus complex that inhabit the south-east (SE) of the Iberian Peninsula and other lineages of the complex remain unclear. In this study, four mitochondrial and two nuclear markers were used to study genetic relationships within this complex. The phylogenetic analyses based on mtDNA gene trees constructed with ML and BI, and a species tree using *BEAST support three divergent clades in this region: the Valencia, Galera and Albacete/Murcia lineages. These three lineages were also corroborated in species delimitation analyses based on mtDNA using bPTP, mPTP, GMYC, ABGD and BAPS. Bayesian inference species delimitation method (BPP) based on both nuclear data and a combined data set (mtDNA + nuclear) showed high posterior probabilities for these three SE lineages (≥0.94) and another Bayesian analysis (STACEY) based on combined data set recovered the same three groups in this region. Divergence time dating of the species tree provided an estimated divergence of the Galera lineage from the other SE group (Podarcis vaucheri, (Albacete/Murcia, Valencia)) at 12.48 Ma. During this period, the Betic–Rifian arc was isolated, which could have caused the isolation of the Galera form distributed to the south of the Betic Corridor. Although lizards from the Albacete/Murcia and Galera lineage are morphologically similar, they clearly represent distinct genetic lineages. The noteworthy separation of the Galera lineage enables us to conclude that this lineage must be considered as a new full species. 相似文献
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Rachel M. Haywood Andrew W. D. Claxson Geoffrey E. Hawkes David P. Richardson Declan P. Naughton Gregory Coumbarides Jane Hawkes Edward J. Lynch Martin C. Grootveld 《Free radical research》1995,22(5):441-482
High field (400 and 600 MHz) proton NMR spectroscopy has been employed to investigate the thermally-induced autoxidation of glycerol-bound polyunsaturated fatty acids present in intact culinary frying oils and fats. Heating of these materials at 180°C for periods of 30, 60 and 90 min. generated a variety of peroxidation products, notably aldehydes (alkanals, trans-2-alkenals and alka-2, 4-dienals) and their conjugated hydroperoxydiene precursors. Since such aldehydes appear to be absorbed into the systemic circulation from the gut in vivo, the toxicological significance of their production during standard frying practices is discussed. 相似文献
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W. T. Brown 《American journal of human genetics》1996,58(5):903
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Davide Danovi Amos Folarin Sabine Gogolok Christine Ender Ahmed M. O. Elbatsh P?r G. Engstr?m Stefan H. Stricker Sladjana Gagrica Ana Georgian Ding Yu Kin Pong U Kevin J. Harvey Patrizia Ferretti Patrick J. Paddison Jane E. Preston N. Joan Abbott Paul Bertone Austin Smith Steven M. Pollard 《PloS one》2013,8(10)
Glioblastoma multiforme (GBM) is the most common primary brain cancer in adults and there are few effective treatments. GBMs contain cells with molecular and cellular characteristics of neural stem cells that drive tumour growth. Here we compare responses of human glioblastoma-derived neural stem (GNS) cells and genetically normal neural stem (NS) cells to a panel of 160 small molecule kinase inhibitors. We used live-cell imaging and high content image analysis tools and identified JNJ-10198409 (J101) as an agent that induces mitotic arrest at prometaphase in GNS cells but not NS cells. Antibody microarrays and kinase profiling suggested that J101 responses are triggered by suppression of the active phosphorylated form of polo-like kinase 1 (Plk1) (phospho T210), with resultant spindle defects and arrest at prometaphase. We found that potent and specific Plk1 inhibitors already in clinical development (BI 2536, BI 6727 and GSK 461364) phenocopied J101 and were selective against GNS cells. Using a porcine brain endothelial cell blood-brain barrier model we also observed that these compounds exhibited greater blood-brain barrier permeability in vitro than J101. Our analysis of mouse mutant NS cells (INK4a/ARF−/−, or p53−/−), as well as the acute genetic deletion of p53 from a conditional p53 floxed NS cell line, suggests that the sensitivity of GNS cells to BI 2536 or J101 may be explained by the lack of a p53-mediated compensatory pathway. Together these data indicate that GBM stem cells are acutely susceptible to proliferative disruption by Plk1 inhibitors and that such agents may have immediate therapeutic value. 相似文献
59.
A Macintosh Hypertalk program (Hypercard stack)for use in phylogenetic comparative analysis of RNA structureis described. The program identifies covariations and compensatorychanges in RNA sequence alignments, for use in the constructionof secondary structure models or the identification of tertiaryinteractions. The results of an analysis are presented eitheras a list of positions in the alignment which covary, or asa 2-dimensional matrix in which potential helices in the secondarystructure appear as diagonal patterns.
Received on January 7, 1991; accepted on March 19, 1991 相似文献
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