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41.
It was previously proposed that plant growth-promoting bacteria that possess 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase could utilize ACC that is present in the exudate of germinating canola seeds. The uptake and cleavage of ACC by these bacteria would lower the level of ACC, and thus ethylene within the plant, and reduce the extent of its inhibition on root elongation. To test part of the above mentioned model, ACC levels were monitored in canola seed tissues and exudate during germination. Lower amounts of ACC were present in the exudate and tissues of seeds treated with the plant growth-promoting bacterium Enterobacter cloacae CAL3, than in control seeds treated with MgSO4. The ACC-related compounds, alpha- and gamma-aminobutyric acids, both known to stimulate ethylene production, were also measured in the canola seed exudate and tissues. Approximately the same levels of alpha-aminobutyric acid were present in the exudates of the bacterium-treated seeds and the control seeds, but the amount of alpha-aminobutyric acid was lower in the tissues of the bacterium-treated seeds than in the control seeds. Smaller quantities of gamma-aminobutyric acid were seen in both the exudate and tissues of the E. cloacae CAL3-treated seeds than in the control seeds. 相似文献
42.
Pinard R Lambert D Heckman JE Esteban JA Gundlach CW Hampel KJ Glick GD Walter NG Major F Burke JM 《Journal of molecular biology》2001,307(1):51-65
The two domains of the hairpin ribozyme-substrate complex, usually depicted as straight structural elements, must interact with one another in order to form an active conformation. Little is known about the internal geometry of the individual domains in an active docked complex. Using various crosslinking and structural approaches in conjunction with molecular modeling (constraint-satisfaction program MC-SYM), we have investigated the conformation of the substrate-binding domain in the context of the active docked ribozyme-substrate complex. The model generated by MC-SYM showed that the domain is not straight but adopts a bent conformation (D-shaped) in the docked state of the ribozyme, indicating that the two helices bounding the internal loop are closer than was previously assumed. This arrangement rationalizes the observed ability of hairpin ribozymes with a circularized substrate-binding strand to cleave a circular substrate, and provides essential information concerning the organization of the substrate in the active conformation. The internal geometry of the substrate-binding strand places G8 of the substrate-binding strand near the cleavage site, which has allowed us to predict the crucial role played by this nucleotide in the reaction chemistry. 相似文献
43.
Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis 总被引:9,自引:0,他引:9
Chu EY Hens J Andl T Kairo A Yamaguchi TP Brisken C Glick A Wysolmerski JJ Millar SE 《Development (Cambridge, England)》2004,131(19):4819-4829
Mammary glands, like other skin appendages such as hair follicles and teeth, develop from the surface epithelium and underlying mesenchyme; however, the molecular controls of embryonic mammary development are largely unknown. We find that activation of the canonical WNT/beta-catenin signaling pathway in the embryonic mouse mammary region coincides with initiation of mammary morphogenesis, and that WNT pathway activity subsequently localizes to mammary placodes and buds. Several Wnt genes are broadly expressed in the surface epithelium at the time of mammary initiation, and expression of additional Wnt and WNT pathway genes localizes to the mammary lines and placodes as they develop. Embryos cultured in medium containing WNT3A or the WNT pathway activator lithium chloride (LiCl) display accelerated formation of expanded placodes, and LiCl induces the formation of ectopic placode-like structures that show elevated expression of the placode marker Wnt10b. Conversely, expression of the secreted WNT inhibitor Dickkopf 1 in transgenic embryo surface epithelium in vivo completely blocks mammary placode formation and prevents localized expression of all mammary placode markers tested. These data indicate that WNT signaling promotes placode development and is required for initiation of mammary gland morphogenesis. WNT signals play similar roles in hair follicle formation and thus may be broadly required for induction of skin appendage morphogenesis. 相似文献
44.
Amphetamine is more effective than methamphetamine at raising dopamine levels in the prefrontal cortex. The current study tested the hypothesis that norepinephrine transporters are involved in this difference. Using microdialysis, dopamine, norepinephrine, and serotonin were measured in the rat prefrontal cortex after administration of methamphetamine or amphetamine, with and without perfusion of desipramine. Amphetamine raised norepinephrine levels more than methamphetamine did. Desipramine raised dopamine and serotonin levels but did not alter metabolite levels. Desipramine attenuated the increase in dopamine by amphetamine while increasing the dopamine released by methamphetamine. These data suggest that methamphetamine and amphetamine differ in altering prefrontal cortical dopamine levels and in interacting with norepinephrine transporters. It is proposed that amphetamine releases dopamine in the prefrontal cortex primarily through norepinephrine transporters, whereas methamphetamine interacts minimally with norepinephrine transporters. 相似文献
45.
46.
The noise level of a high-throughput screening (HTS) experiment depends on various factors such as the quality and robustness of the assay itself and the quality of the robotic platform. Screening of compound mixtures is noisier than screening single compounds per well. A classification model based on na?ve Bayes (NB) may be used to enrich such data. The authors studied the ability of the NB classifier to prioritize noisy primary HTS data of compound mixtures (5 compounds/well) in 4 campaigns in which the percentage of noise presumed to be inactive compounds ranged between 81% and 91%. The top 10% of the compounds suggested by the classifier captured between 26% and 45% of the active compounds. These results are reasonable and useful, considering the poor quality of the training set and the short computing time that is needed to build and deploy the classifier. 相似文献
47.
Soderholm J Bhattacharyya D Strongin D Markovitz V Connerly PL Reinke CA Glick BS 《Developmental cell》2004,6(5):649-659
COPII vesicles assemble at ER subdomains called transitional ER (tER) sites, but the mechanism that generates tER sites is unknown. To study tER biogenesis, we analyzed the transmembrane protein Sec12, which initiates COPII vesicle formation. Sec12 is concentrated at discrete tER sites in the budding yeast Pichia pastoris. We find that P. pastoris Sec12 exchanges rapidly between tER sites and the general ER. The tER localization of Sec12 is saturable and is mediated by interaction of the Sec12 cytosolic domain with a partner component. This interaction apparently requires oligomerization of the Sec12 lumenal domain. Redistribution of P. pastoris Sec12 to the general ER does not perturb the localization of downstream tER components, suggesting that Sec12 and other COPII proteins associate with a tER scaffold. These results provide evidence that tER sites form by a network of dynamic associations at the cytosolic face of the ER. 相似文献
48.
Hepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion 总被引:4,自引:0,他引:4
Amigo L Zanlungo S Miquel JF Glick JM Hyogo H Cohen DE Rigotti A Nervi F 《Journal of lipid research》2003,44(2):399-407
We examined in vivo a role for sterol carrier protein-2 (SCP-2) in the regulation of lipid secretion across the hepatic sinusoidal and canalicular membranes. Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice. We determined plasma, hepatic, and biliary lipid concentrations; hepatic fatty acid (FA) and cholesterol synthesis; hepatic and biliary phosphatidylcholine (PC) molecular species; and VLDL triglyceride production. In Ad.rSCP2 mice, there was marked inhibition of hepatic fatty acids and cholesterol synthesis to <62% of control mice. Hepatic triglyceride contents were decreased, while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. As expected, biliary cholesterol, phospholipids, bile acids outputs, and biliary PC hydrophobic index were significantly increased in Ad.rSCP2 mice. These studies indicate that SCP-2 overexpression in the liver markedly inhibits lipid synthesis as well as VLDL production, and alters hepatic lipid contents. In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile. These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes. 相似文献
49.
11F8 is a murine anti-ssDNA monoclonal autoantibody isolated from a lupus prone autoimmune mouse. This mAb binds sequence specifically, and prior studies have defined the thermodynamic and kinetic basis for sequence-specific recognition of ssDNA (Ackroyd, P. C., et al. (2001) Biochemistry 40, 2911-2922; Beckingham, J. A. and Glick, G. D. (2001) Bioorg. Med. Chem. 9, 2243-2252). Here we present experiments designed to identify the residues on 11F8 that mediate sequence-specific, noncognate, and nonspecific recognition of ssDNA and their contribution to the overall binding thermodynamics. Site-directed mutagenesis of an 11F8 single-chain construct reveals that six residues within the complementarity determining regions of 11F8 account for ca. 80% of the binding free energy and that there is little cooperativity between these residues. Germline-encoded aromatic and hydrophobic side chains provides the basis for nonspecific recognition of single-stranded thymine nucleobases. Sequence-specific recognition is controlled by a tyrosine in the heavy chain along with a somatically mutated arginine residue. Our data show that the manner in which 11F8 achieves sequence-specific recognition more closely resembles RNA-binding proteins such as U1A than other types of nucleic acid binding proteins. In addition, comparing the primary sequence of 11F8 with clonally related antibodies that differ by less than five amino acids suggests that somatic mutations which confer sequence specificity may be a feature that distinguishes glomerulotrophic pathogenic anti-DNA from those that are benign. 相似文献
50.