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排序方式: 共有239条查询结果,搜索用时 31 毫秒
51.
Huffman JW Bushell SM Joshi SN Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2006,14(1):247-262
Two new series of cannabinoids were prepared and their affinities for the CB1 and CB2 receptors were determined. These series are the (2'R)- and (2'S)-1-methoxy- and 1-deoxy-3-(2'-methylalkyl)-delta8-tetrahydrocannabinols, with alkyl side chains of three to seven carbon atoms. These compounds were prepared by a route that employed the enantioselective synthesis of the resorcinol precursors to the cannabinoid ring system. All of these compounds have greater affinity for the CB2 receptor than the CB1 receptor and four of them, (2'R)-1-methoxy-3-(2'-methylbutyl)-delta8-THC (JWH-359), (2'S)-1-deoxy-3-(2'-methylbutyl)-delta8-THC (JWH-352), (2'S)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), and (2'R)-1-deoxy-3-(2'-methylpentyl)-delta8-THC (JWH-255), have good affinity (K(i) = 13-47 nM) for the CB2 receptor and little affinity (K(i) = 1493 to >10,000 nM) for the CB1 receptor. In the 1-deoxy-3-(2'-methylalkyl)-delta8-THC series, the 2'S-methyl compounds in general have greater affinity for the CB2 receptor than the corresponding 2'R isomers. 相似文献
52.
53.
ABSTRACT: Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its support values follow a similar scale and its receiver-operating characteristics are nearly identical, indicating that it provides similar levels of sensitivity and specificity. Thus our assessment method makes it possible to conduct phylogenetic analyses on whole genomes with the same degree of confidence as for analyses on aligned sequences. Extensions to search-based inference methods such as maximum parsimony and maximum likelihood are possible, but remain to be thoroughly tested. 相似文献
54.
David Lindsay Downie Francisco Vicente-Agullo Antonio Campos-Caro Trevor John Bushell William Robert Lieb Nicholas Peter Franks 《The Journal of biological chemistry》2002,277(12):10367-10373
Some neurotransmitter-gated ion channels are very much more sensitive to general anesthetics than others, even when they are genetically and structurally related. The most striking example of this is the extreme sensitivity of heteromeric neuronal nicotinic acetylcholine receptors to inhalational general anesthetics compared with the marked insensitivity of the closely related homomeric neuronal nicotinic receptors. Here we investigate the role of the alpha subunit in determining the anesthetic sensitivity of these receptors by using alpha(3)/alpha(7) chimeric subunits that are able to form functional homomeric receptors. By comparing the sensitivities of a number of chimeras to the inhalational agent halothane we show that the short (13 amino acids) putative extracellular loop connecting the second and third transmembrane segments is a critical determinant of anesthetic sensitivity. In addition, using site-directed mutagenesis, we show that two particular amino acids in this loop play a dominant role. When mutations are made in this loop, there is a good correlation between increasing anesthetic sensitivity and decreasing acetylcholine sensitivity. We conclude that this extracellular loop probably does not participate directly in anesthetic binding, but rather determines receptor sensitivity indirectly by playing a critical role in transducing anesthetic binding into an effect on channel gating. 相似文献
55.
56.
Anastasiia Kamenska Wei-Ting Lu Dorota Kubacka Helen Broomhead Nicola Minshall Martin Bushell Nancy Standart 《Nucleic acids research》2014,42(5):3298-3313
A key player in translation initiation is eIF4E, the mRNA 5′ cap-binding protein. 4E-Transporter (4E-T) is a recently characterized eIF4E-binding protein, which regulates specific mRNAs in several developmental model systems. Here, we first investigated the role of its enrichment in P-bodies and eIF4E-binding in translational regulation in mammalian cells. Identification of the conserved C-terminal sequences that target 4E-T to P-bodies was enabled by comparison of vertebrate proteins with homologues in Drosophila (Cup and CG32016) and Caenorhabditis elegans by sequence and cellular distribution. In tether function assays, 4E-T represses bound mRNA translation, in a manner independent of these localization sequences, or of endogenous P-bodies. Quantitative polymerase chain reaction and northern blot analysis verified that bound mRNA remained intact and polyadenylated. Ectopic 4E-T reduces translation globally in a manner dependent on eIF4E binding its consensus Y30X4Lϕ site. In contrast, tethered 4E-T continued to repress translation when eIF4E-binding was prevented by mutagenesis of YX4Lϕ, and modestly enhanced the decay of bound mRNA, compared with wild-type 4E-T, mediated by increased binding of CNOT1/7 deadenylase subunits. As depleting 4E-T from HeLa cells increased steady-state translation, in part due to relief of microRNA-mediated silencing, this work demonstrates the conserved yet unconventional mechanism of 4E-T silencing of particular subsets of mRNAs. 相似文献
57.
Contribution of sucrose synthase, ADP-glucose pyrophosphorylase and starch synthase to starch synthesis in developing pea seeds 总被引:11,自引:0,他引:11
Using genetic variability existing amongst nine pea genotypes (Pisum sativum L.), the biochemical basis of sink strength in developing pea seeds was investigated. Sink strength was considered to be reflected by the rate of starch synthesis (RSS) in the embryo, and sink activity in the seed was reflected by the relative rate of starch synthesis (RRSS). These rates were compared to the activities of three enzymes of the starch biosynthetic pathway [sucrose synthase (Sus), ADP-glucose pyrophosphorylase and starch synthase] at three developmental stages during seed filling (25, 50 and 75% of the dry seed weight). Complete sets of data collected during seed filling for the nine genotypes showed that, for all enzyme activities (expressed on a protein basis), only Sus in the embryo and seed coat was linearly and significantly correlated to RRSS. The contribution of the three enzyme activities to the variability in RSS and RRSS was evaluated by multiple regression analysis for the first two developmental stages. Only Sus activity in the embryo could explain, at least in part, the significant variability observed for both the RSS and the RRSS at each developmental stage. We conclude that Sus activity is a reliable marker of sink activity in developing pea seeds. 相似文献
58.
Sea urchin Hox genes: insights into the ancestral Hox cluster 总被引:3,自引:0,他引:3
We describe the Hox cluster in the radially symmetric sea urchin and
compare our findings to what is known from clusters in bilaterally
symmetric animals. Several Hox genes from the direct-developing sea urchin
Heliocidaris erythrogramma are described. CHEF gel analysis shows that the
Hox genes are clustered on a < or = 300 kilobase (kb) fragment of DNA,
and only a single cluster is present, as in lower chordates and other
nonvertebrate metazoans. Phylogenetic analyses of sea urchin, amphioxus,
Drosophila, and selected vertebrate Hox genes confirm that the H.
erythrogramma genes, and others previously cloned from other sea urchins,
belong to anterior, central, and posterior groups. Despite their radial
body plan and lack of cephalization, echinoderms retain at least one of the
anterior group Hox genes, an orthologue of Hox3. The structure of the
echinoderm Hox cluster suggests that the ancestral deuterostome had a Hox
cluster more similar to the current chordate cluster than was expected Sea
urchins have at least three Abd-B type genes, suggesting that Abd-B
expansion began before the radiation of deuterostomes.
相似文献
59.
Rumelo Amor Alison McDonald Johanna Tr?g?rdh Gillian Robb Louise Wilson Nor Zaihana Abdul Rahman John Dempster William Bradshaw Amos Trevor J. Bushell Gail McConnell 《PloS one》2016,11(1)
We demonstrate fluorescence imaging by two-photon excitation without scanning in biological specimens as previously described by Hwang and co-workers, but with an increased field size and with framing rates of up to 100 Hz. During recordings of synaptically-driven Ca2+ events in primary rat hippocampal neurone cultures loaded with the fluorescent Ca2+ indicator Fluo-4 AM, we have observed greatly reduced photo-bleaching in comparison with single-photon excitation. This method, which requires no costly additions to the microscope, promises to be useful for work where high time-resolution is required. 相似文献
60.
Thérèse S Lapperre Jacob K Sont Annemarie van Schadewijk Margot ME Gosman Dirkje S Postma Ingeborg M Bajema Wim Timens Thais Mauad Pieter S Hiemstra 《Respiratory research》2007,8(1):85-9