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George V. Sharonov Eduard V. Bocharov Peter M. Kolosov Maria V. Astapova Alexander S. Arseniev Alexey V. Feofanov 《The Journal of biological chemistry》2014,289(21):14955-14964
The EphA2 receptor tyrosine kinase plays a central role in the regulation of cell adhesion and guidance in many human tissues. The activation of EphA2 occurs after proper dimerization/oligomerization in the plasma membrane, which occurs with the participation of extracellular and cytoplasmic domains. Our study revealed that the isolated transmembrane domain (TMD) of EphA2 embedded into the lipid bicelle dimerized via the heptad repeat motif L535X3G539X2A542X3V546X2L549 rather than through the alternative glycine zipper motif A536X3G540X3G544 (typical for TMD dimerization in many proteins). To evaluate the significance of TMD interactions for full-length EphA2, we substituted key residues in the heptad repeat motif (HR variant: G539I, A542I, G553I) or in the glycine zipper motif (GZ variant: G540I, G544I) and expressed YFP-tagged EphA2 (WT, HR, and GZ variants) in HEK293T cells. Confocal microscopy revealed a similar distribution of all EphA2-YFP variants in cells. The expression of EphA2-YFP variants and their kinase activity (phosphorylation of Tyr588 and/or Tyr594) and ephrin-A3 binding were analyzed with flow cytometry on a single cell basis. Activation of any EphA2 variant is found to occur even without ephrin stimulation when the EphA2 content in cells is sufficiently high. Ephrin-A3 binding is not affected in mutant variants. Mutations in the TMD have a significant effect on EphA2 activity. Both ligand-dependent and ligand-independent activities are enhanced for the HR variant and reduced for the GZ variant compared with the WT. These findings allow us to suggest TMD dimerization switching between the heptad repeat and glycine zipper motifs, corresponding to inactive and active receptor states, respectively, as a mechanism underlying EphA2 signal transduction. 相似文献
3.
Anna Pugatshova ülle Kikas Margit Prüssel Aivo Reinart Eduard Tamm et al. 《Plant Growth Regulation》1991,10(2):177-178
Book Review
Principles of environmental physicsJ.L. Monteith and M.H. Unsworth Second edition. London: Edward Arnold, 1990. xii + 291 pages. £30.00 (hardback), £14.95 (paperback). ISBN 0-7131-2931-X 相似文献4.
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A 330 bp region of the spinach nitrite reductase gene promoter directs nitrate-inducible tissue-specific expression in transgenic tobacco 总被引:4,自引:0,他引:4
7.
Roger S. McIntyre Mohammad Alsuwaidan Bernhard T. Baune Michael Berk Koen Demyttenaere Joseph F. Goldberg Philip Gorwood Roger Ho Siegfried Kasper Sidney H. Kennedy Josefina Ly-Uson Rodrigo B. Mansur R. Hamish McAllister-Williams James W. Murrough Charles B. Nemeroff Andrew A. Nierenberg Joshua D. Rosenblat Gerard Sanacora Alan F. Schatzberg Richard Shelton Stephen M. Stahl Madhukar H. Trivedi Eduard Vieta Maj Vinberg Nolan Williams Allan H. Young Mario Maj 《World psychiatry》2023,22(3):394-412
Treatment-resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision-making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision-making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo-resistant (e.g., due to inadequacy of treatment trials or non-adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non-response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co-administered with an antidepressant) are established as efficacious in the management of TRD. Some second-generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine-fluoxetine combination has been studied in FDA-defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA-approved for individuals with TRD, with accelerated theta-burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non-inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual-based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population. 相似文献
8.
Summary Iodination of proteins and lipoproteins is a widely used in vitro labelling procedure in metabolic, autoradiographic and various other studies. However, all available iodination techniques have involved the possible damage to the proteins by self-irradiation, oxidizing agents, the alkaline milieu or by the introduction of iodine into the molecular structure itself. To evaluate the integrity of iodinated lipoproteins, we observed the electron microscopic appearance of normal and iodinated rabbit very low density lipoproteins (VLDL) by negative staining with phosphotungstic acid. Iodination up to a molar iodine/protein ratio of 2.89 did not result in any change of shape, size or aggregating tendency of the particles. No stacks or disk-like particles like those of various hyperlipoproteinemic states were found. We conclude that electron microscopy is a valuable tool in assessing the morphological appearance of lipoprotein iodination, but it should be complemented by other techniques. 相似文献
9.
Eduard Kühn Rudi Van Cauwenbergh Leo Huybrechts Hendrik Deelstra 《Biological trace element research》1992,32(1-3):289-292
Plasma concentrations of cGH, T3, and T4 were not different between dwarf and normal broiler breeders. Normal hens had a liver selenium content of 710±35 ng/g, and
dwarf hens 656 ±nine ng/g (n=8). Following injections into a wing vein of different doses (1.5, 3, 6, 12, and 24 μg/kg) of the hypothalamic hormone TRH,
GH was increased after 15 min. This effect seemed to last longer in dwarf chickens. Plasma concentrations of T3 increased significantly 1 h after TRH in normal hens, but TRH was ineffective in raising T3 levels in dwarf animals. The selenium content of livers obtained following decapitation after 2 h was also increased in normal
hens up to 902±42 ng/g using the highest dose of TRH (24 μg/kg). This seemed not to be the case for dwarf animals. A much
smaller. number of hepatic cGH receptors was also found in dwarf hens, whereas the affinity of the hepatic GH receptor was
not influenced by the genotype. It is concluded that the sex-linked dwarf hens are unable to increase their hepatic T4 into T3 conversion following a TRH challenge probably because of a deficiency in hepatic GH receptors. The lower content of selenium
in dwarfs and their inability to increase its uptake after TRH seem therefore to support the hypothesis that selenium has
a direct role in the activity of the 5′-deiodinase complex. 相似文献
10.
Dagmar Jičínská Eduard Brabec Marcel Rejmánek Jan Jeník Joří Haager Josef Holub Věroslav Samek Hana Rambousková Josef Holub Marie Naděžda Končalová Robert Neuhäusl Josev Kyncl František Krahuleo Jaroslav Dobrý Blanka Úlehlová Jiří Úlehla Eliška Rybníčková Kamil Rybníček 《Folia Geobotanica》1982,17(4):431-448