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41.
Piatnitski EL Duncton MA Kiselyov AS Katoch-Rouse R Sherman D Milligan DL Balagtas C Wong WC Kawakami J Doody JF 《Bioorganic & medicinal chemistry letters》2005,15(21):4696-4698
A novel class of 4-arylamino-phthalazin-1-yl-benzamides is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Several compounds display potent VEGFR-2 inhibitory activity with an IC50 as low as 0.078 microM in an HTRF enzymatic assay. These compounds are relatively selective against a small kinase panel. 相似文献
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Mire Convery Caitríona Dennis Sin Rowsell Andreas Engel J Bernard Heymann Gary Parkinson Rob Russell Gianfranco Gilardi Richard Newman Irmgard Sinning Sabine Flitsch Philip AS Lowden Steve Matthews Gerard J Kleywegt Jon D Stewart 《Current opinion in structural biology》1999,9(6):653
A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in structural biology. 相似文献
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The highly polarized nature of epithelial cells in exocrine glands necessitates targeting, assembly into complexes and confinement of the molecules comprising the Ca(2+) signaling apparatus, to cellular microdomains. Such high degree of polarized localization has been shown for all Ca(2+) signaling molecules tested, including G protein coupled receptors and their associated proteins, Ca(2+) pumps, Ca(2+) influx channels at the plasma membrane and Ca(2+) release channels in the endoplasmic reticulum. Although the physiological significance of polarized Ca(2+) signaling is clear, little is known about the mechanism of targeting, assembly and retention of Ca(2+) signaling complexes in cellular microdomains. The present review attempts to summarize the evidence in favor of polarized expression of Ca(2+) signaling proteins at the apical pole of secretory cells with emphasis on the role of scaffolding proteins in the assembly and function of the Ca(2+) signaling complexes. The consequence of polarized enrichment of Ca(2+) signaling complexes at the apical pole is generation of an apical to basal pole gradient of cell responsiveness that, at low physiological agonist concentrations, limits Ca(2+) spikes to the apical pole, and when a Ca(2+) wave occurs, it always propagates from the apical to the basal pole. Our understanding of Ca(2+) signaling in microdomains is likely to increase rapidly with the application of techniques to controllably and selectively disrupt components of the complexes and apply high resolution recording techniques, such as TIRF microscopy to this problem. 相似文献
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Long-term effects of ungulates on phytophagous insects 总被引:1,自引:0,他引:1
Abstract. 1. Most plants interact with a diverse suite of herbivores, allowing the opportunity for the existence of positive and negative interactions between highly dissimilar organisms. However, most studies on herbivorous interactions have been performed under the assumption that they occur mainly between similar species. Consequently, ecologists are still far from a full understanding of the ecological factors that determine insect population dynamics.
2. In this study, a 7-year field experiment was conducted that manipulated the presence of ungulates to evaluate their effects on the abundance, attack rate, and survival of four guilds of co-occurring herbivorous insects living on the same host plant: seed predators, stem borers, gall makers and sap suckers. These four guilds differed in habits and behaviour, the first three being sessile and endophytic and the last being free-living.
3. This study shows that the abundance of all four guilds was negatively affected by ungulates. However, the effect on attack rate differed among guilds, as mammals do not affect the seed predator attack rate. Ungulates also differentially affected insect survival, ingesting only seed predators and gall makers.
4. In summary, this study suggests that diverse mechanisms may affect different insect guilds in different ways. Therefore, competition between disparate herbivores appears to be complex and can be provoked by multiple mechanisms. 相似文献
2. In this study, a 7-year field experiment was conducted that manipulated the presence of ungulates to evaluate their effects on the abundance, attack rate, and survival of four guilds of co-occurring herbivorous insects living on the same host plant: seed predators, stem borers, gall makers and sap suckers. These four guilds differed in habits and behaviour, the first three being sessile and endophytic and the last being free-living.
3. This study shows that the abundance of all four guilds was negatively affected by ungulates. However, the effect on attack rate differed among guilds, as mammals do not affect the seed predator attack rate. Ungulates also differentially affected insect survival, ingesting only seed predators and gall makers.
4. In summary, this study suggests that diverse mechanisms may affect different insect guilds in different ways. Therefore, competition between disparate herbivores appears to be complex and can be provoked by multiple mechanisms. 相似文献
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L C R?nn M Olsen S Ostergaard V Kiselyov V Berezin M T Mortensen M H Lerche P H Jensen V Soroka J L Saffell P Doherty F M Poulsen E Bock A Holm J L Saffells 《Nature biotechnology》1999,17(10):1000-1005
The neural cell adhesion molecule (NCAM) plays a key role in neural development, regeneration, and learning. In this study, we identified a synthetic peptide-ligand of the NCAM Ig1 module by combinatorial chemistry and showed it could modulate NCAM-mediated cell adhesion and signal transduction with high potency. In cultures of dissociated neurons, this peptide, termed C3, stimulated neurite outgrowth by activating a signaling pathway identical to that activated by homophilic NCAM binding. A similar effect was shown for the NCAM Ig2 module, the endogenous ligand of NCAM Ig1. By nuclear magnetic resonance spectroscopy, the C3 binding site in the NCAM Ig1 module was mapped and shown to be different from the binding site of the NCAM Ig2 module. The C3 peptide may prove useful as a lead in development of therapies for neurodegenerative disorders, and the C3 binding site of NCAM Ig1 may represent a target for discovery of nonpeptide drugs. 相似文献
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