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Williams BJ Cascieri MA Chicchi GG Harrison T Owens AP Owen SN Rupniak NM Tattersall DF Williams A Swain CJ 《Bioorganic & medicinal chemistry letters》2002,12(19):2719-2722
A series of novel spiroether-based neurokinin-1 (NK(1)) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration. 相似文献
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MP Lisovoi NM Lesovoy GI Vasechko 《Archives Of Phytopathology And Plant Protection》2013,46(2):123-127
A new method of selection of the winter wheat varieties has been tested for resistance to the pest insects' complex by the traits of plants that are the markers of plant resistance. It makes it possible to use this method from year to year independently of the pests' density. 相似文献
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Juraj Culman Stephan Mühlenhoff Annegret Blume Jürgen Hedderich Ulf Lützen Stephen P. Hunt Nadia M. J. Rupniak Yi Zhao 《Cellular and molecular neurobiology》2018,38(6):1271-1281
Mice lacking the substance P (SP) neurokinin-1 (NK1) receptor (NK1R?/?mice) were used to investigate whether SP affects serotonin (5-HT) function in the brain and to assess the effects of acute immobilisation stress on the hypothalamic–pituitary–adrenocortical (HPA) axis and 5-HT turnover in individual brain nuclei. Basal HPA activity and the expression of hypothalamic corticotropin-releasing hormone (CRH) in wild-type (WT)- and NK1R?/? mice were identical. Stress-induced increases in plasma ACTH concentration were considerably higher in NK1R?/? mice than in WT mice while corticosterone concentrations were equally elevated in both mouse lines. Acute stress did not alter the expression of CRH. In the dorsal raphe nucleus (DRN), basal 5-HT turnover was increased in NK1R?/? mice and a 15 min stress further magnified 5-HT utilisation in this region. In the frontoparietal cortex, medial prefrontal cortex, central nucleus of amygdala, and the hippocampal CA1 region, stress increased 5-HT and/or 5-hydroxyindoleacetic acid (5-HIAA) concentrations to a similar extent in WT and NK1R?/? mice. 5-HT turnover in the hypothalamic paraventricular nucleus was not affected by stress, but stress induced similar increases in 5-HT and 5-HIAA in the ventromedial and dorsomedial hypothalamic nuclei in WT and NK1R?/? mice. Our findings indicate that NK1 receptor activation suppresses ACTH release during acute stress but does not exert sustained inhibition of the HPA axis. Genetic deletion of the NK1 receptor accelerates 5-HT turnover in DRN under basal and stress conditions. No differences between the responses of serotonergic system to acute stress in WT and NK1R?/? mice occur in forebrain nuclei linked to the regulation of anxiety and neuroendocrine stress responses. 相似文献
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Growth stimulation of either fetal rat liver cells or rat embryo fibroblasts in culture results in considerable increases in intracellular polyamine levels as cells proceed through the cell cycle. Treatment of such cell cultures with appropriate levels of two inhibitors of polyamine synthesis, namely α-hydrazino ornithine and methylglyoxal bis(guanylhydrazone), can essentially completely block these increases in cellular polyamine content. Under such conditions, where the elevation in intracellular polyamine content is prevented, cell cultures are nevertheless able to initiate DNA synthesis and subsequently synthesize DNA at rates comparable to untreated control cultures that have been growth-stimulated. These two cell types therefore contain sufficient polyamines when in a resting state (G1) to enable them to enter from G1 into S phase and traverse S phase at normal rates in the absence of further polyamine synthesis. The recruitment of cells into the first cell cycle, through serum stimulation of growth, therefore appears not to be mediated or regulated by the increases in intracellular levels of polyamines that occurs under these conditions. Conversely, the arrest of growth of these cell types resulting from serum deprivation is not mediated by a limitation of intracellular polyamine content. 相似文献
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Dieter Paul Kenneth D. Brown H. Thomas Rupniak H. J. Ristow 《In vitro cellular & developmental biology. Plant》1978,14(1):76-84
Summary SV3T3 cells, originally responsive to epidermal growth factor (EGF) and displaying density-dependent inhibition of growth,
lose responsiveness to the growth factor after several passages and then proliferate without restriction, but continue to
display EGF receptor sites at the cell surface. Proliferation of primary fetal rat hepatocytes is not stimulated by EGF, but
cells bind it to an extent comparable to that of responsive 3T3 cells. Therefore presence of EGF receptors does not imply
that cells are responsive to the growth factor. The relevance of some growth-factor-induced events for DNA synthesis initiation
is dicussed. In various primary and secondary cell cultures, Ca++-levels appear to be involved in controlling cell proliferation. In contrast, in 3T3-4a cells, levels of Ca++ ions are not tightly coupled to DNA synthesis initiation; effects of growth factors are not mediated by extracellular Ca++ ions, but cells have a Ca++-sensitive restriction, point in G1. In various cell types in primary or secondary culture or in 3T3-4a cells, polyamine, levels are not tightly coupled to induction
of proliferation. Therefore growth-factor-induced ornithine decarboxylase is not an event essential for DNA synthesis initiation.
Normal but not transformed cells have a spermidine/spermine-sensitive restriction point in G1. Although rRNA synthesis appears to be necessary for induction of proliferation, preliminary data obtained by double-beam
flow microfluorometry suggest that cellular RNA levels might not affect rate of entry into S phase and, furthermore, that
3T3-4a cells can enter S without accumulating RNA above levels present in quiescent cells. It appears that none of the events
induced during the prereplicative phase that have been studied in 3T3 cells are essential for DNA synthesis initiation under
normal culture conditions.
Presented in the Opening Symposium on Nutritional Factors and Differentiation at the 28th Annual Meeting of the Tissue Culture
Association, New Orleans, Louisiana, June 6–9, 1977.
This work was supported by Research Grants GM 20101, CA 15087, CA 14195, CA 12227 and CA 11176 from the USPHS, and Grant BC-30D
from the American Cancer Society. 相似文献
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Adriaan D Bins Jacco van Rheenen Kees Jalink Jonathan R Halstead Nullin Divecha David M Spencer John BAG Haanen Ton NM Schumacher 《BMC biotechnology》2007,7(1):2
Background
Advances in fluorescence microscopy and mouse transgenesis have made it possible to image molecular events in living animals. However, the generation of transgenic mice is a lengthy process and intravital imaging requires specialized knowledge and equipment. Here, we report a rapid and undemanding intravital imaging method using generally available equipment. 相似文献29.
Background
The frequency of a haplotype comprising one allele at each of two loci can be expressed as a cubic equation (the 'Hill equation'), the solution of which gives that frequency. Most haplotype and linkage disequilibrium analysis programs use iteration-based algorithms which substitute an estimate of haplotype frequency into the equation, producing a new estimate which is repeatedly fed back into the equation until the values converge to a maximum likelihood estimate (expectation-maximisation). 相似文献30.
Purified chloroplast tRNAs were isolated fromPisum sativum leaves and radioactively labeled at their 3′ end using tRNA nucleotidyl transferase and α32P-labeled CTP. Pea ctDNA was fragmented using a number of restriction endonucleases and hybridized with thein vitro labeled chloroplast tRNAs by DNA transfer method. Genes for tRNAs have been found to be dispersed throughout the chloroplast
genome. A closer analysis of the several hybrid regions using recombinant DNA plasmids have shown that tRNA genes are localized
in the chloroplast genome in both single and multiple arrangements. Two dimensional gel electrophoresis of total ct tRNA have
identified 36 spots. All of them have been found to hybridize withPisum sativum ctDNA. Using recombinant clones, 30 of the tRNA spots have been mapped inPisum sativum ctDNA. 相似文献