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941.
Bewley MS Pena JT Plesch FN Decker SE Weber GJ Forrest JN 《American journal of physiology. Regulatory, integrative and comparative physiology》2006,291(4):R1157-R1164
Vasoactive intestinal peptide (VIP) is a secretagogue that mediates chloride secretion in intestinal epithelia. We determined the relative potency of VIP and related peptides in the rectal gland of the elasmobranch dogfish shark and cloned and expressed the VIP receptor (sVIP-R) from this species. In the perfused rectal gland, VIP (5 nM) stimulated chloride secretion from 250 +/- 66 to 2,604 +/- 286 microeq x h(-1) x g(-1); the relative potency of peptide agonists was VIP > PHI = GHRH > PACAP > secretin, where PHI is peptide histidine isoleucine amide, GHRH is growth hormone-releasing hormone, and PACAP is pituitary adenylate cylase activating peptide. The cloned sVIP-R from shark rectal gland (SRG) is only 61% identical to the human VIP-R1. It maintains a long, extracellular NH2 terminus with seven cysteine residues, and has three N-glycosylation sites and eight other residues implicated in VIP binding. Two amino acids considered important for peptide binding in mammals are not present in the shark orthologue. When sVIP-R and the CFTR chloride channel were coexpressed in Xenopus oocytes, VIP increased chloride conductance from 11.3 +/- 2 to 127 +/- 34 microS. The agonist affinity for activating chloride conductance by the cloned receptor was VIP > GHRH = PHI > PACAP > secretin, a profile mirroring that in the perfused gland. The receptor differs from previously cloned VIP-Rs in having a low affinity for PACAP. Expression of both sVIP-R and CFTR mRNA was detected by quantitative PCR in shark rectal gland, intestine, and brain. These studies characterize a unique G protein-coupled receptor from the shark rectal gland that is the oldest cloned VIP-R. 相似文献
942.
Shojaiefard M Christie DL Lang F 《Biochemical and biophysical research communications》2006,341(4):945-949
Cellular accumulation of creatine is accomplished by the Na(+), Cl(-), and creatine transporter CreaT (SLC6A8). The mammalian target of rapamycin (mTOR) is a kinase stimulating cellular nutrient uptake. The present experiments explored whether SLC6A8 is regulated by mTOR. In Xenopus oocytes expressing SLC6A8 but not in water injected oocytes, creatine-induced a current which was significantly enhanced by coexpression of mTOR. Kinetic analysis revealed that mTOR enhanced maximal current without significantly altering affinity. Preincubation of the oocytes for 32 h with rapamycin (50 nM) decreased the creatine-induced current and abrogated its stimulation by mTOR. The effect of mTOR on CreaT was blunted by additional coexpression of the inactive mutant of the serum and glucocorticoid-inducible kinase (K119N)SGK1 and mimicked by coexpression of wild type SGK1. In conclusion, mTOR stimulates the creatine transporter SLC6A8 through mechanisms at least partially shared by the serum and glucocorticoid-inducible kinase SGK1. 相似文献
943.
Cell biology of molybdenum 总被引:7,自引:0,他引:7
The transition element molybdenum (Mo) is of essential importance for (nearly) all biological systems as it is required by enzymes catalyzing diverse key reactions in the global carbon, sulfur and nitrogen metabolism. The metal itself is biologically inactive unless it is complexed by a special cofactor. With the exception of bacterial nitrogenase, where Mo is a constituent of the FeMo-cofactor, Mo is bound to a pterin, thus forming the molybdenum cofactor (Moco) which is the active compound at the catalytic site of all other Mo-enzymes. In eukaryotes, the most prominent Mo-enzymes are (1) sulfite oxidase, which catalyzes the final step in the degradation of sulfur-containing amino acids and is involved in detoxifying excess sulfite, (2) xanthine dehydrogenase, which is involved in purine catabolism and reactive oxygen production, (3) aldehyde oxidase, which oxidizes a variety of aldehydes and is essential for the biosynthesis of the phytohormone abscisic acid, and in autotrophic organisms also (4) nitrate reductase, which catalyzes the key step in inorganic nitrogen assimilation. All Mo-enzymes, except plant sulfite oxidase, need at least one more redox active center, many of them involving iron in electron transfer. The biosynthesis of Moco involves the complex interaction of six proteins and is a process of four steps, which also includes iron as well as copper in an indispensable way. Moco as released after synthesis is likely to be distributed to the apoproteins of Mo-enzymes by putative Moco-carrier proteins. Xanthine dehydrogenase and aldehyde oxidase, but not sulfite oxidase and nitrate reductase, require the post-translational sulfuration of their Mo-site for becoming active. This final maturation step is catalyzed by a Moco-sulfurase enzyme, which mobilizes sulfur from l-cysteine in a pyridoxal phosphate-dependent manner as typical for cysteine desulfurases. 相似文献
944.
Jonathan Fray M Bish G Brown AD Fish PV Stobie A Wakenhut F Whitlock GA 《Bioorganic & medicinal chemistry letters》2006,16(16):4345-4348
The synthesis and structure-activity relationships of a novel series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake is described. Two compounds possessed comparable in vitro profiles to the dual reuptake inhibitor duloxetine. 相似文献
945.
Fray MJ Bish G Fish PV Stobie A Wakenhut F Whitlock GA 《Bioorganic & medicinal chemistry letters》2006,16(16):4349-4353
We report the structure-activity relationships of further analogues in a series of piperazine derivatives as dual inhibitors of serotonin and noradrenaline reuptake, that is, with additional substitution of the phenyl rings, or their replacement by heterocycles. The enantiomers of compounds 1 and 2 were also profiled, and possessed drug-like physicochemical properties. In particular, compound (-)-2 lacked potent inhibitory activity against any of the important cytochromes P(450) and high selectivity over a wide range of receptors, which is unusual for a compound that inhibits human amine transporters. 相似文献
946.
947.
Maderspacher F 《Current biology : CB》2006,16(13):R476-R478
In the 'Origin of Species', Darwin sums up his ideas about the evolutionary process in a single diagram. Tracing the 'evolution' of this diagram reveals a host of sources that may have inspired Darwin's imagination. 相似文献
948.
Gametophytic self-incompatibility (SI) systems in plants exhibit high polymorphism at the SI controlling S-locus because individuals with rare alleles have a higher probability to successfully pollinate other plants than individuals with more frequent alleles. This process, referred to as frequency-dependent selection, is expected to shape number, frequency distribution, and spatial distribution of self-incompatibility alleles in natural populations. We investigated the genetic diversity and the spatial genetic structure within a Prunus avium population at two contrasting gene loci: nuclear microsatellites and the S-locus. The S-locus revealed a higher diversity (15 alleles) than the eight microsatellites (4-12 alleles). Although the frequency distribution of S-alleles differed significantly from the expected equal distribution, the S-locus showed a higher evenness than the microsatellites (Shannon's evenness index for the S-locus: E = 0.91; for the microsatellites: E = 0.48-0.83). Also, highly significant deviations from neutrality were found for the S-locus whereas only minor deviations were found for two of eight microsatellites. A comparison of the frequency distribution of S-alleles in three age-cohorts revealed no significant differences, suggesting that different levels of selection acting on the S-locus or on S-linked sites might also affect the distribution and dynamics of S-alleles. Autocorrelation analysis revealed a weak but significant spatial genetic structure for the multilocus average of the microsatellites and for the S-locus, but could not ascertain differences in the extent of spatial genetic structure between these locus types. An indirect estimate of gene dispersal, which was obtained to explain this spatial genetic pattern, indicated high levels of gene dispersal within our population (sigma(g) = 106 m). This high gene dispersal, which may be partly due to the self-incompatibility system itself, aids the effective gene flow of the microsatellites, thereby decreasing the contrast between the neutral microsatellites and the S-locus. 相似文献
949.
Bis(ferrocenyl)-substituted allenylidene complexes, [(CO)5MCCCFc2] (1a-c, Fc = (C5H4)Fe(C5H5), M = Cr (a), Mo (b), W (c)) were obtained by sequential reaction of Fc2CO with Me3Si-CCH, KF/MeOH, n-BuLi, and [(CO)5M(THF)]. For the synthesis of related mono(ferrocenyl)allenylidene chromium complexes, [(CO)5CrCCC(Fc)R] (R = Ph, NMe2), three different routes were developed: (a) reaction of the deprotonated propargylic alcohol HCCC(Fc)(Ph)OH with [(CO)5Cr(THF)] followed by desoxygenation with Cl2CO, (b) Lewis acid induced alcohol elimination from alkenyl(alkoxy)carbene complexes, [(CO)5CrC(OR)CHC(NMe2)Fc], and (c) replacement of OMe in [(CO)5CrCCC(OMe)NMe2] by Fc. Complex 1a was also formed when the mono(ferrocenyl)allenylidene complex [(CO)5CrCCC(Fc)NMe2] was treated first with Li[Fc] and the resulting adduct then with SiO2. The replacement route (c) was also applied to the synthesis of an allenylidene complex (7a) with a CC spacer in between the ferrocenyl unit and Cγ of the allenylidene ligand, [(CO)5CrCCC(NMe2)-CCFc]. The related complex containing a CHCH spacer (9a) was prepared by condensation of [(CO)5CrCCC(Me)NMe2] with formylferrocene in the presence of NEt3. The bis(ferrocenyl)-substituted allenylidene complexes 1a-c added HNMe2 across the Cα-Cβ bond to give alkenyl(dimethylamino)carbene complexes and reacted with diethylaminopropyne by regioselective insertion of the CC bond into the Cβ-Cγ bond to afford alkenyl(diethylamino)allenylidene complexes, [(CO)5MCCC(NEt2)CMeCFc2]. The structures of 5a, 7a, and 9a were established by X-ray diffraction studies. 相似文献
950.
The evolution of floral scent: the influence of olfactory learning by insect pollinators on the honest signalling of floral rewards 总被引:5,自引:1,他引:4
1. The evolution of flowering plants has undoubtedly been influenced by a pollinator's ability to learn to associate floral signals with food. Here, we address the question of 'why' flowers produce scent by examining the ways in which olfactory learning by insect pollinators could influence how floral scent emission evolves in plant populations.
2. Being provided with a floral scent signal allows pollinators to learn to be specific in their foraging habits, which could, in turn, produce a selective advantage for plants if sexual reproduction is limited by the income of compatible gametes. Learning studies with honeybees predict that pollinator-mediated selection for floral scent production should favour signals which are distinctive and exhibit low variation within species because these signals are learned faster. Social bees quickly learn to associate scent with the presence of nectar, and their ability to do this is generally faster and more reliable than their ability to learn visual cues.
3. Pollinators rely on floral scent as a means of distinguishing honestly signalling flowers from deceptive ones. Furthermore, a pollinator's sensitivity to differences in nectar rewards can bias the way that it responds to floral scent. This mechanism may select for flowers that provide olfactory signals as an honest indicator of the presence of nectar or which select against the production of a detectable scent signal when no nectar is present.
4. We expect that an important yet commonly overlooked function of floral scent is an improvement in short-term pollinator specificity which provides an advantage to both pollinator and plant over the use of a visual signal alone. This, in turn, impacts the evolution of plant mating systems via its influence on the species-specific patterns of floral visitation by pollinators. 相似文献
2. Being provided with a floral scent signal allows pollinators to learn to be specific in their foraging habits, which could, in turn, produce a selective advantage for plants if sexual reproduction is limited by the income of compatible gametes. Learning studies with honeybees predict that pollinator-mediated selection for floral scent production should favour signals which are distinctive and exhibit low variation within species because these signals are learned faster. Social bees quickly learn to associate scent with the presence of nectar, and their ability to do this is generally faster and more reliable than their ability to learn visual cues.
3. Pollinators rely on floral scent as a means of distinguishing honestly signalling flowers from deceptive ones. Furthermore, a pollinator's sensitivity to differences in nectar rewards can bias the way that it responds to floral scent. This mechanism may select for flowers that provide olfactory signals as an honest indicator of the presence of nectar or which select against the production of a detectable scent signal when no nectar is present.
4. We expect that an important yet commonly overlooked function of floral scent is an improvement in short-term pollinator specificity which provides an advantage to both pollinator and plant over the use of a visual signal alone. This, in turn, impacts the evolution of plant mating systems via its influence on the species-specific patterns of floral visitation by pollinators. 相似文献