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951.
Els Lommelen Tom Wenseleers Christine A. Johnson Falko P. Drijfhout Johan Billen Bruno Gobin 《Journal of Insect Behavior》2010,23(3):236-249
Approximately 150 ant species are facultatively or obligately queenless whereby mated workers assume the role of the queen.
In many of these species a reproductive dominance hierarchy is established by way of aggressive interactions. Top-ranking
workers, which are typically the most fecund, acquire a characteristic cuticular hydrocarbon profile. We studied the temporal
dynamics of this chemical change and associated interplay with observed aggressive interactions in an experimentally orphaned
colony of the facultatively queenless ant Gnamptogenys striatula. Our observations and chemical analyses demonstrate that chemical fertility signals played a major role in the establishment
of a dominance hierarchy and aggression settled dominance relationships only when ants had identical hydrocarbon profiles.
Moreover, individuals with a higher potential fertility, in this experiment reflected in a higher ovariole number, are shown
to have a better chance of becoming a reproductive. 相似文献
952.
Billie A. Moore Gladys D. Gonzalez Aviles Christine E. Larkins Michael J. Hillman Tamara Caspary 《Mammalian genome》2010,21(7-8):350-360
Mitochondria are dynamic cellular organelles that balance fission and fusion to regulate organelle morphology, distribution, and activity, and Opa1 is one of three GTPases known to regulate mitochondrial fusion. In humans, loss of a single Opa1 allele causes dominant optic atrophy, a degenerative condition that leads to loss of vision. Here we demonstrate that the lilR3 mutant mouse phenotype is due to a point mutation in the Opa1 gene resulting in mislocalized Opa1 protein from the mitochondria to the cytosol. Importantly, the mutation is in the middle domain of the Opa1 protein, for which no function had been described. Lack of mitochondrial retention of Opa1 is sufficient to cause the cellular Opa1 loss-of-function phenotype as the mitochondria are fragmented, indicating an inability to fuse. Despite the normally ubiquitous expression of Opa1 and the essential nature of mitochondria, embryos with aberrant Opa1 survived through midgestation and died at E11.5. These mutants displayed growth retardation, exencephaly, and abnormal patterning along the anterior-posterior axis, although the A–P axis itself was intact. The complex relationship between mitochondrial dynamics and cell death is emphasized by apoptosis in specific cell populations of lilR3 embryos. Our results define, for the first time, a function of the middle domain of the Opa1 protein and demonstrate that mitochondrial retention of Opa1 protein is essential for normal embryogenesis. 相似文献
953.
954.
Increases in the environmental osmolarity are key determinants for the growth of microorganisms. To ensure a physiologically acceptable level of cellular hydration and turgor at high osmolarity, many bacteria accumulate compatible solutes. Osmotically controlled uptake systems allow the scavenging of these compounds from scarce environmental sources as effective osmoprotectants. A number of these systems belong to the BCCT family (betaine-choline-carnitine-transporter), sodium- or proton-coupled transporters (e.g. BetP and BetT respectively) that are ubiquitous in microorganisms. The BCCT family also contains CaiT, an L-carnitine/γ-butyrobetaine antiporter that is not involved in osmotic stress responses. The glycine betaine transporter BetP from Corynebacterium glutamicum is a representative for osmoregulated symporters of the BCCT family and functions both as an osmosensor and osmoregulator. The crystal structure of BetP in an occluded conformation in complex with its substrate glycine betaine and two crystal structures of CaiT in an inward-facing open conformation in complex with L-carnitine and γ-butyrobetaine were reported recently. These structures and the wealth of biochemical data on the activity control of BetP in response to osmotic stress enable a correlation between the sensing of osmotic stress by a transporter protein with the ensuing regulation of transport activity. Molecular determinants governing the high-affinity binding of the compatible solutes by BetP and CaiT, the coupling in symporters and antiporters, and the osmoregulatory properties are discussed in detail for BetP and various BCCT carriers. 相似文献
955.
Potter A Oldfield V Nunns C Fromont C Ray S Northfield CJ Bryant CJ Scrace SF Robinson D Matossova N Baker L Dokurno P Surgenor AE Davis B Richardson CM Murray JB Moore JD 《Bioorganic & medicinal chemistry letters》2010,20(22):6483-6488
Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential. 相似文献
956.
Christine E. Brotherton-Pleiss Michael P. Dillon Anthony P.D.W. Ford Joel R. Gever David S. Carter Shelley K. Gleason Clara J. Lin Amy G. Moore Anthony W. Thompson Marzia Villa Yansheng Zhai 《Bioorganic & medicinal chemistry letters》2010,20(3):1031-1036
Despite the extensive literature describing the role of the ATP-gated P2X3 receptors in a variety of physiological processes the potential of antagonists as therapeutic agents has been limited by the lack of drug-like selective molecules. In this paper we report the discovery and optimization of RO-85, a novel drug-like, potent and selective P2X3 antagonist. High-throughput screening of the Roche compound collection identified a small hit series of heterocyclic amides from a large parallel synthesis library. Rapid optimization, facilitated by high-throughput synthesis, focusing on increasing potency and improving drug-likeness resulted in the discovery of RO-85. 相似文献
957.
Laszlo Revesz Achim Schlapbach Reiner Aichholz Janet Dawson Roland Feifel Stuart Hawtin Amanda Littlewood-Evans Guido Koch Markus Kroemer Henrik Möbitz Clemens Scheufler Juraj Velcicky Christine Huppertz 《Bioorganic & medicinal chemistry letters》2010,20(15):4719-4723
Spirocyclopropane- and spiroazetidine-substituted tetracycles 13D–E and 16A are described as orally active MK2 inhibitors. The spiroazetidine derivatives are potent MK2 inhibitors with IC50 <3 nM and inhibit the release of TNFα (IC50<0.3 μM) from hPBMCs and hsp27 phosphorylation in anisomycin stimulated THP-1 cells. The spirocyclopropane analogues are less potent against MK2 (IC50 = 0.05–0.23 μM), less potent in cells (IC50 <1.1 μM), but show good oral absorption. Compound 13E (100 mg/kg po; bid) showed oral activity in rAIA and mCIA, with significant reduction of swelling and histological score. 相似文献
958.
Wu TY Juteau H Ducharme Y Friesen RW Guiral S Dufresne L Poirier H Salem M Riendeau D Mancini J Brideau C 《Bioorganic & medicinal chemistry letters》2010,20(23):6978-6982
Microsomal prostaglandin E(2) synthase (mPGES-1) represents a potential target for novel analgesic and anti-inflammatory agents. High-throughput screening identified several leads of mPGES-1 inhibitors which were further optimized for potency and selectivity. A series of inhibitors bearing a biaryl imidazole scaffold exhibits excellent inhibition of PGE(2) production in enzymatic and cell-based assays. The synthesis of these molecules and their activities will be discussed. 相似文献
959.
Emily M. Stocking Leah Aluisio John R. Atack Pascal Bonaventure Nicholas I. Carruthers Christine Dugovic Anita Everson Ian Fraser Xiaohui Jiang Perry Leung Brian Lord Kiev S. Ly Kirsten L. Morton Diane Nepomuceno Chandravadan R. Shah Jonathan Shelton Akinola Soyode-Johnson Michael A. Letavic 《Bioorganic & medicinal chemistry letters》2010,20(9):2755-2760
Pre-clinical characterization of novel substituted pyrrolidines that are high affinity histamine H3 receptor antagonists is described. These compounds efficiently penetrate the CNS and occupy the histamine H3 receptor in rat brain following oral administration. One compound, (2S,4R)-1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy)-pyrrolidin-1-yl]-ethanone, was extensively profiled and shows promise as a potential clinical candidate. 相似文献
960.
Robert R. Singhaus Ronald C. Bernotas Robert Steffan Edward Matelan Elaine Quinet Ponnal Nambi Irene Feingold Christine Huselton Anna Wilhelmsson Annika Goos-Nilsson Jay Wrobel 《Bioorganic & medicinal chemistry letters》2010,20(2):521-525
Replacement of a quinoline with an imidazo[1,2-a]pyridine in a series of liver X receptor (LXR) agonists incorporating a [3-(sulfonyl)aryloxyphenyl] side chain provided high affinity LXR ligands 7. In functional assays of LXR activity, good agonist potency and efficacy were found for several analogs. 相似文献