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61.
In the circadian timing systems, input pathways transmit information on the diurnal environmental changes to a core oscillator that generates signals relayed to the body periphery by output pathways. Cryptochrome (CRY) protein participates in the light perception; period (PER), Cycle (CYC), and Doubletime (DBT) proteins drive the core oscillator; and arylalkylamines are crucial for the clock output in vertebrates. Using antibodies to CRY, PER, CYC, DBT, and arylalkylamine N-acetyltransferase (aaNAT), the authors examined neuronal architecture of the circadian system in the cephalic ganglia of adult silkworms. The antibodies reacted in the cytoplasm, never in the nuclei, of specific neurons. A cluster of 4 large Ia(1) neurons in each dorsolateral protocerebrum, a pair of cells in the frontal ganglion, and nerve fibers in the corpora cardiaca and corpora allata were stained with all antibodies. The intensity of PER staining in the Ia(1) cells and in 2 to 4 adjacent small cells oscillated, being maximal late in subjective day and minimal in early night. No other oscillations were detected in any cell and with any antibody. Six small cells in close vicinity to the Ia(1) neurons coexpressed CYC-like and DBT-like, and 4 to 5 of them also coexpressed aaNATlike immunoreactivity; the PER- and CRY-like antigens were each present in separate groups of 4 cells. The CYC- and aaNAT-like antigens were further colocalized in small groups of neurons in the pars intercerebralis, at the venter of the optic tract, and in the subesophageal ganglion. Remaining antibodies reacted with similarly positioned cells in the pars intercerebralis, and the DBT antibody also reacted with the cells in the subesophageal ganglion, but antigen colocalizations were not proven. The results imply that key components of the silkworm circadian system reside in the Ia(1) neurons and that additional, hierarchically arranged oscillators contribute to overt pacemaking. The retrocerebral neurohemal organs seem to serve as outlets transmitting central neural oscillations to the hemolymph. The frontal ganglion may play an autonomous function in circadian regulations. The colocalization of aaNAT- and CYC-like antigens suggests that the enzyme is functionally linked to CYC as in vertebrates and that arylalkylamines are involved in the insect output pathway. 相似文献
62.
3alpha,17beta-Dihydroxy-3beta-methyl-5alpha-androstan-6-one (1) and 3beta,17beta-dihydroxy-3alpha-methyl-5alpha-androstan-6-one (13) were prepared by the reaction of methylmagnesium bromide with the 3-ketosteroids. Structures and configurations in position 3 were determined by NMR spectra. Substitution in the position 6 influences the ratio of the products. 相似文献
63.
Simultaneous determination of dehydroepiandrosterone, its 7-hydroxylated metabolites, and their sulfates in rat brain tissues 总被引:4,自引:0,他引:4
A method is described for simultaneous assessment of dehydroepiandrosterone (DHEA), its sulfate (DHEAS), and their 7-hydroxylated metabolites in cortex and subcortex of the rat brain. The procedure for determination of unconjugated steroids and DHEAS involved diethyl ether extraction of the homogenized tissue, solvent partition of the dry extract, and final quantification by specific radioimmunoassays. In addition, determination of 7-hydroxy-dehydroepiandrosterone sulfates required solvolysis, followed by high-performance liquid chromatography for separation of 7-hydroxylated metabolites from their precursor. The losses during this process were monitored by measurement of spiked radioactivity of [(3)H]testosterone or [(3)H]dehydroepiandrosterone sulfate. The content of dehydroepiandrosterone sulfate in both brain tissues was of the order of ten(s) nmol/g tissue irrespective its type (cortex or subcortex), while concentrations of other steroids were about 10 times lower in both tissues. In contrast to the ratio of sulfated/unconjugated DHEA, the levels of unconjugated 7-hydroxylated metabolites and their sulfates were close to each other. The reproducibility of the method with respect to coefficients of variation varied from 12 to 25%. An age-related decrease of sulfated dehydroepiandrosterone in the cortex of animals was also observed. 相似文献
64.
Adámková H Vicar J Palasová J Ulrichová J Simánek V 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2004,148(1):103-105
A double-blind, placebo-controlled clinical trial was performed to investigate the effectiveness of a herbal-based dentifrice in the control of gingivitis. Forty volunteers completed the 84-day study. All subjects were balanced for parameters measured - plaque index (PI), community periodontal index of treatment needs (CPITN) and papillary bleeding index (PBI). The dentifrice was effective in reducing symptoms of gingivitis as evaluated by the CPITN and PBI indexes. 相似文献
65.
Study of Saccharomyces cerevisiae killer toxin-sensitive strains with the deltakre2 phenotype (resistant to toxin K1, sensitive to toxin K2) showed that the phenotype is complemented by the KRE2 gene not only in intact cells but also in spheroplasts, and resistance to K1 thus resides very probably in the plasma membrane. deltakre1 deletant displays a faulty interaction with both K1 and K2 toxin. Hence, Kre1p probably serves as plasma membrane receptor for both toxins. Deletants in seven other genes (GDA1, SAC1, LUV1, KRE23, SAC2, KRE21, ERG4) exhibit different degrees of the deltakre2-like resistance pattern, but the phenotype in deltagda1 and deltasac1 is not connected with a defect in K1 toxin interaction with the plasma membrane, similarly as in deltakre6 and deltakre11 strains with a higher resistance to K2 toxin. Differences between the K1 and K2 killer toxin thus occur on the level of both the plasma membrane and the cell wall. 相似文献
66.
alpha(1)-Antitrypsin is the most abundant protease inhibitor in plasma and is the archetype of the serine protease inhibitor superfamily. Genetic variants of human alpha(1)-antitrypsin are associated with early-onset emphysema and liver cirrhosis. However, the detailed molecular mechanism for the pathogenicity of most variant alpha(1)-antitrypsin molecules is not known. Here we examined the structural basis of a dozen deficient alpha(1)-antitrypsin variants. Unlike most alpha(1)-antitrypsin variants, which were unstable, D256V and L41P variants exhibited extremely retarded protein folding as compared with the wild-type molecule. Once folded, however, the stability and inhibitory activity of these variant proteins were comparable to those of the wild-type molecule. Retarded protein folding may promote protein aggregation by allowing the accumulation of aggregation-prone folding intermediates. Repeated observations of retarded protein folding indicate that it is an important mechanism causing alpha(1)-antitrypsin deficiency by variant molecules, which have to fold into the metastable native form to be functional. 相似文献
67.
Conejo-Garcia JR Benencia F Courreges MC Kang E Mohamed-Hadley A Buckanovich RJ Holtz DO Jenkins A Na H Zhang L Wagner DS Katsaros D Caroll R Coukos G 《Nature medicine》2004,10(9):950-958
The involvement of immune mechanisms in tumor angiogenesis is unclear. Here we describe a new mechanism of tumor vasculogenesis mediated by dendritic cell (DC) precursors through the cooperation of beta-defensins and vascular endothelial growth factor-A (Vegf-A). Expression of mouse beta-defensin-29 recruited DC precursors to tumors and enhanced tumor vascularization and growth in the presence of increased Vegf-A expression. A new leukocyte population expressing DC and endothelial markers was uncovered in mouse and human ovarian carcinomas coexpressing Vegf-A and beta-defensins. Tumor-infiltrating DCs migrated to tumor vessels and independently assembled neovasculature in vivo. Bone marrow-derived DCs underwent endothelial-like differentiation ex vivo, migrated to blood vessels and promoted the growth of tumors expressing high levels of Vegf-A. We show that beta-defensins and Vegf-A cooperate to promote tumor vasculogenesis by carrying out distinct tasks: beta-defensins chemoattract DC precursors through CCR6, whereas Vegf-A primarily induces their endothelial-like specialization and migration to vessels, which is mediated by Vegf receptor-2. 相似文献
68.
One of the major challenges in the post-genome era is the correlation between genes and function or phenotype. We have pioneered a strategy for screening of cDNA libraries, which is based on sequential combination of lentiviral and oncoretroviral expression systems and can be used to identify proliferation-modulating genes. Screening of a lentiviral expression library derived from adult human brain cDNA resulted in cloning of the potent proliferation-inducing determinant termed pi1 (proliferation inducer 1). Transduction experiments using GFP-expressing oncoretroviruses to target proliferation-competent cells suggested that overexpression of pi1 initiates proliferation of human umbilical vein endothelial cells (HUVECs). Growth induction of HUVECs as well as Swiss3T3 fibroblasts was confirmed by Brd-uridine incorporation assays, which correlated increased DNA synthesis with expression of pi1. The identified pi1 cDNA is 297 bp long and encodes a 10 kDa polypeptide. Since deregulation of proliferation control accounts for a number of today’s untreatable human diseases such as neurodegenerative disorders and cancer, discovery of novel proliferation-modulating genes is essential for developing new strategies for gene therapy and tissue engineering. 相似文献
69.
Data presented in this paper show that the size of the endogenous coenzyme Q (CoQ) pool is not a limiting factor in the activation of mitochondrial glycerophosphate-dependent respiration by exogenous CoQ(3), since successive additions of succinate and NADH to brown adipose tissue mitochondria further increase the rate of oxygen uptake. Because the inhibition of glycerophosphate-dependent respiration by oleate was eliminated by added CoQ(3), our data indicate that the activating effect of CoQ(3) is related to the release of the inhibitory effect of endogenous free fatty acids (FFA). Both the inhibitory effect of FFA and the activating effect of CoQ(3) could be demonstrated only for glycerophosphate-dependent respiration, while succinate- or NADH-dependent respiration was not affected. The presented data suggest differences between mitochondrial glycerophosphate dehydrogenase and succinate or NADH dehydrogenases in the transfer of reducing equivalents to the CoQ pool. 相似文献
70.
Purinergic receptors (P2XRs) activate and desensitize in response to the binding of extracellular nucleotides in a receptor- and ligand-specific manner, but the structural bases of their ligand preferences and channel kinetics have been incompletely characterized. Here we tested the hypothesis that affinity of agonists for binding domain accounts for a ligand-specific desensitization pattern. We generated chimeras using receptors with variable sensitivity to ATP in order: P2X(4)R > P2X(2a)R = P2X(2b)R P2X(7)R. Chimeras having the ectodomain Ile(66)-Tyr(310) sequence of P2X(2)R and Val(61)-Phe(313) sequence of P2X(7)R in the backbone of P2X(4)R were expressed but were non-functioning channels. P2X(2a) + X(4)R and P2X(2b) + X(4)R chimeras having the Val(66)-Tyr(315) ectodomain sequence of P2X(4)R in the backbones of P2X(2a)R and P2X(2b)R were functional and exhibited increased sensitivity to ligands as compared with both parental receptors. These chimeras also desensitized faster than parental receptors and in a ligand-nonspecific manner. However, like parental P2X(2b)R and P2X(2a)R, chimeric P2X(2b) + X(4)R desensitized more rapidly than P2X(2a) + X(4)R, and the rate of desensitization of P2X(2a)+X(4)R increased by substituting its Arg(371)-Pro(376) intracellular C-terminal sequence with the Glu(376)-Gly(381) sequence of P2X(4)R. These results indicate the relevance of interaction between the ectodomain and flanking regions around the transmembrane domains on ligand potency and receptor activation. Furthermore, the ligand potency positively correlates with the rate of receptor desensitization but does not affect the C-terminal-specific pattern of desensitization. 相似文献