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71.
Renault J Bernard A Brajeul S Verhaeghe P Butt S Fabis F Dauphin F Uriac P Rault S 《Journal of enzyme inhibition and medicinal chemistry》2004,19(6):577-583
A series of N-omega-aminoalkyl- or N-omega-amidinoalkyl-2,4,6-triisopropyl benzenesulfonamides has been synthesized and their respective affinity indices on 5-HT6 receptor determined. This evaluation clearly showed that the compounds possessing an arylpiperazine moiety or an amidine function exhibited good affinity for the model. 相似文献
72.
Terradot L Durnell N Li M Li M Ory J Labigne A Legrain P Colland F Waksman G 《Molecular & cellular proteomics : MCP》2004,3(8):809-819
We have investigated a large set of interactions from the Helicobacter pylori protein interaction map previously identified by high-throughput yeast two-hybrid (htY2H)-based methods. This study had two aims: i) to validate htY2H as a source of protein-protein interaction complexes for high-throughput biochemical and structural studies of the H. pylori interactome; and ii) to validate biochemically interactions shown by htY2H to involve components of the H. pylori type IV secretion systems. Thus, 17 interactions involving 31 proteins and protein fragments were studied, and a general strategy was designed to produce protein-interacting partners for biochemical and structural characterization. We show that htY2H is a valid source of protein-protein complexes for high-throughput proteome-scale characterization of the H. pylori interactome, because 76% of the interactions tested were confirmed biochemically. Of the interactions involving type IV secretion proteins, three could be confirmed. One interaction is between two components of the type IV secretion apparatus, ComB10 and ComB4, which are VirB10 and VirB4 homologs, respectively. Another interaction is between a type IV component (HP0525, a VirB11 homolog) and a non-type IV secretion protein (HP01451), indicating that proteins other than the core VirB (1-11)-VirD4 proteins may play a role in type IV secretion. Finally, a third interaction was biochemically confirmed between CagA, a virulence factor secreted by the type IV secretion system encoded by the Cag pathogenicity island, and a non-type IV secretion protein, HP0496. 相似文献
73.
Austerlitz F Dick CW Dutech C Klein EK Oddou-Muratorio S Smouse PE Sork VL 《Molecular ecology》2004,13(4):937-954
Pollen dispersal is a critical process that shapes genetic diversity in natural populations of plants. Estimating the pollen dispersal curve can provide insight into the evolutionary dynamics of populations and is essential background for making predictions about changes induced by perturbations. Specifically, we would like to know whether the dispersal curve is exponential, thin-tailed (decreasing faster than exponential), or fat-tailed (decreasing slower than the exponential). In the latter case, rare events of long-distance dispersal will be much more likely. Here we generalize the previously developed TWOGENER method, assuming that the pollen dispersal curve belongs to particular one- or two-parameter families of dispersal curves and estimating simultaneously the parameters of the dispersal curve and the effective density of reproducing individuals in the population. We tested this method on simulated data, using an exponential power distribution, under thin-tailed, exponential and fat-tailed conditions. We find that even if our estimates show some bias and large mean squared error (MSE), we are able to estimate correctly the general trend of the curve - thin-tailed or fat-tailed - and the effective density. Moreover, the mean distance of dispersal can be correctly estimated with low bias and MSE, even if another family of dispersal curve is used for the estimation. Finally, we consider three case studies based on forest tree species. We find that dispersal is fat-tailed in all cases, and that the effective density estimated by our model is below the measured density in two of the cases. This latter result may reflect the difficulty of estimating two parameters, or it may be a biological consequence of variance in reproductive success of males in the population. Both the simulated and empirical findings demonstrate the strong potential of TWOGENER for evaluating the shape of the dispersal curve and the effective density of the population (d(e)). 相似文献
74.
It has been reported that auxin induces an epinastic growth response in plant leaf tissues. Leaf strips of tobacco (Nicotiana tabacum L. 'Bright Yellow 2') were used to study the effects of indole-3-acetic acid (IAA), the principal form of auxin in higher plants, and a synthetic auxin, 2,4-dichlorophenoxyacetic acid (2,4-D), on epinastic leaf curvature. Incubation of leaf strips with 10 micro M IAA resulted in a marked epinastic curvature response. Unexpectedly, 2,4-D showed only a weak IAA-like activity in inducing epinasty. Interestingly, the presence of 2,4-D resulted in inhibition of the IAA-dependent epinastic curvature. In vivo Lineweaver-Burk kinetic analysis clearly indicated that the interaction between IAA and 2,4-D reported here is not a result of competitive inhibition. Using kinetic analysis, it was not possible to determine whether the mode of interaction between IAA and 2,4-D was non-competitive or uncompetitive. 2,4-D inhibits the IAA-dependent epinasty via complex and as yet unidentified mechanisms. 相似文献
75.
El-Sayed NM Ghedin E Song J MacLeod A Bringaud F Larkin C Wanless D Peterson J Hou L Taylor S Tweedie A Biteau N Khalak HG Lin X Mason T Hannick L Caler E Blandin G Bartholomeu D Simpson AJ Kaul S Zhao H Pai G Van Aken S Utterback T Haas B Koo HL Umayam L Suh B Gerrard C Leech V Qi R Zhou S Schwartz D Feldblyum T Salzberg S Tait A Turner CM Ullu E White O Melville S Adams MD Fraser CM Donelson JE 《Nucleic acids research》2003,31(16):4856-4863
76.
The wood anatomy of 16 of the 37 genera within the epacrids (Styphelioideae, Ericaceae s.l.) is investigated by light and scanning electron microscopy. Several features in the secondary xylem occur consistently at the tribal level: arrangement of vessel-ray pits, distribution of axial parenchyma, ray width, and the presence and location of crystals. The primitive nature of Prionoteae and Archerieae is supported by the presence of scalariform perforation plates with many bars and scalariform to opposite vessel pitting. The wood structure of Oligarrheneae is similar to that of Styphelieae, but the very narrow vessel elements, exclusively uniseriate rays and the lack of prismatic crystals in Oligarrheneae distinguish these two tribes. The secondary xylem of Monotoca tamariscina indicates that it does not fit in Styphelieae; a position within Oligarrheneae is possible. Like most Cosmelieae, all Richeeae are characterized by exclusively scalariform perforation plates with many bars, a very high vessel density and paratracheal parenchyma, although they clearly differ in ray width (exclusively uniseriate rays in Cosmelieae vs. uniseriate and wide multiseriate rays in Richeeae). Several wood anatomical features confirm the inclusion of epacrids in Ericaceae s.l. Furthermore, there are significant ecological implications. The small vessel diameter and high vessel frequency in many epacrids are indicative of a high conductive safety to avoid embolism caused by freeze-thaw cycles, while the replacement of scalariform by simple vessel perforation plates and an increase in vessel diameter would suggest an increased conductive efficiency, which is especially found in mesic temperate or tropical Styphelieae. 相似文献
77.
In this article, we provide direct evidence for injection of venom by a wasp into the central nervous system of its cockroach prey. Venomous predators use neurotoxins that generally act at the neuromuscular junction, resulting in different types of prey paralysis. The sting of the parasitoid wasp Ampulex compressa is unusual, as it induces grooming behavior, followed by a long-term lethargic state of its insect prey, thus ultimately providing a living meal for the newborn wasp larvae. These behavioral modifications are induced only when a sting is inflicted into the head. These unique effects of the wasp venom on prey behavior suggest that the venom targets the insect's central nervous system. The mechanism by which behavior modifying compounds in the venom transverse the blood-brain barrier to induce these central and long-lasting effects has been the subject of debate. In this article, we demonstrate that the wasp stings directly into the target ganglia in the head of its prey. To prove this assertion, we produced "hot" wasps by injecting them with (14)C radiolabeled amino acids and used a combination of liquid scintillation and light microscopy autoradiography to trace radiolabeled venom in the prey. To our knowledge, this is the first direct evidence documenting targeted delivery of venom by a predator into the brain of its prey. 相似文献
78.
79.
Billich A Bornancin F Dévay P Mechtcheriakova D Urtz N Baumruker T 《The Journal of biological chemistry》2003,278(48):47408-47415
The immunomodulatory drug FTY720 is phosphorylated in vivo, and the resulting FTY720 phosphate as a ligand for sphingosine-1-phosphate receptors is responsible for the unique biological effects of the compound. So far, phosphorylation of FTY720 by murine sphingosine kinase (SPHK) 1a had been documented. We found that, while FTY720 is also phosphorylated by human SPHK1, the human type 2 isoform phosphorylates the drug 30-fold more efficiently, because of a lower Km of FTY720 for SPHK2. Similarly, murine SPHK2 was more efficient than SPHK1a. Among splice variants of the human SPHKs, an N-terminally extended SPHK2 isoform was even more active than SPHK2 itself. Further SPHK superfamily members, namely ceramide kinase and a "SPHK-like" protein, failed to phosphorylate sphingosine and FTY720. Thus, only SPHK1 and 2 appear to be capable of phosphorylating FTY720. Using selective assay conditions, SPHK1 and 2 activities in murine tissues were measured. While activity of SPHK2 toward sphingosine was generally lower than of SPHK1, FTY720 phosphorylation was higher under conditions favoring SPHK2. In human endothelial cells, while activity of SPHK1 toward sphingosine was 2-fold higher than of SPHK2, FTY720 phosphorylation was 7-fold faster under SPHK2 assay conditions. Finally, FTY720 was poorly phosphorylated in human blood as compared with rodent blood, in line with the low activity of SPHK1 and in particular of SPHK2 in human blood. To conclude, both SPHK1 and 2 are capable of phosphorylating FTY720, but SPHK2 is quantitatively more important than SPHK1. 相似文献
80.
Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis 总被引:30,自引:0,他引:30
Li Y Hansotia T Yusta B Ris F Halban PA Drucker DJ 《The Journal of biological chemistry》2003,278(1):471-478
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion and augments beta cell mass via activation of beta cell proliferation and islet neogenesis. We examined whether GLP-1 receptor signaling modifies the cellular susceptibility to apoptosis. Mice administered streptozotocin (STZ), an agent known to induce beta cell apoptosis, exhibit sustained improvement in glycemic control and increased levels of plasma insulin with concomitant administration of the GLP-1 agonist exendin-4 (Ex-4). Blood glucose remained significantly lower for weeks after cessation of exendin-4. STZ induced beta cell apoptosis, which was significantly reduced by co-administration of Ex-4. Conversely, mice with a targeted disruption of the GLP-1 receptor gene exhibited increased beta cell apoptosis after STZ administration. Exendin-4 directly reduced cytokine-induced apoptosis in purified rat beta cells exposed to interleukin 1beta, tumor necrosis fator alpha, and interferon gamma in vitro. Furthermore, Ex-4-treated BHK-GLP-1R cells exhibited significantly increased cell viability, reduced caspase activity, and decreased cleavage of beta-catenin after treatment with cycloheximide in vitro. These findings demonstrate that GLP-1 receptor signaling directly modifies the susceptibility to apoptotic injury, and provides a new potential mechanism linking GLP-1 receptor activation to preservation or enhancement of beta cell mass in vivo. 相似文献