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61.
In response to light, most retinal neurons exhibit gradual changes in membrane potential. Therefore K+ channels that mediate threshold currents are well-suited for the fine-tuning of signal transduction. In the present study we demonstrate the expression of the different Kv11 (ether-à-go-go related gene; erg) channel subunits in the human and mouse retina by RT PCR and quantitative PCR, respectively. Immunofluorescence analysis with cryosections of mouse retinae revealed the following local distribution of the three Kv11 subunits: Kv11.1 (m-erg1) displayed the most abundant expression with the strongest immunoreactivity in rod bipolar cells. In addition, immunoreactivity was found in the inner part of the outer plexiform layer (OPL), in the inner plexiform layer (IPL) and in the inner segments of photoreceptors. Immunoreactivity for Kv11.2 (m-erg2) was observed in the outer part of the OPL and throughout the IPL. Double-labeling for vGluT1 or synaptophysin indicated a mainly presynaptic localization of Kv11.2. While no significant staining for Kv11.3 (m-erg3) was detected in the neuronal retina, strong Kv11.3 immunoreactivity was present in the apical membrane of the retinal pigment epithelium. The different expression levels were confirmed by real-time PCR showing almost equal levels of Kv11.1 and Kv11.2, while Kv11.3 mRNA expression was significantly lower. The two main splice variants of Kv11.1, isoforms a and b were detected in comparable levels suggesting a possible formation of cGMP/cGK-sensitive Kv11.1 channels in photoreceptors and rod bipolar cells. Taken together, the immunohistological results revealed different expression patterns of the three Kv11 channels in the mouse retina supposing distinct physiological roles. 相似文献
62.
Zmojdzian M Dziewulska-Szwajkowska D Dzugaj A 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2005,140(1):37-43
Fructose 1,6-bisphosphatase (FBPase; EC 3.1.3.11) localization in cardiomyocyte nuclei has recently been investigated in mammals [FEBS Lett. 539 (2003) 51]. In this study, nuclear localization of FBPase in the cardiac muscle of the chicken was studied by immunohistochemistry and other methods. A result of the electron microscopic investigation was confirmed by immunoblotting analysis. Using MALDI Q-TOF mass spectrometry and Mascot program, the nuclear FBPase was identified as muscle chicken FBPase. FBPase activity in isolated cardiomyocyte nuclei was 5.9 mU/g. Nuclear FBPase was strongly inhibited by allosteric inhibitor AMP. I(0.5) for AMP was 0.16 microM and was the same as for the purified chicken muscle enzyme. 相似文献
63.
Bayne EH Rakitina DV Morozov SY Baulcombe DC 《The Plant journal : for cell and molecular biology》2005,44(3):471-482
RNA silencing in transgenic and virus-infected plants involves a mobile silencing signal that can move cell-to-cell and systemically through the plant. It is thought that this signal can influence long-distance movement of viruses because protein suppressors of silencing encoded in viral genomes are required for long-distance virus movement. However, until now, it was not known whether the mobile signal could also influence short-range virus movement between cells. Here, through random mutation analysis of the Potato Potexvirus X (PVX) silencing suppressor P25, we provide evidence that it does. All mutants that were defective for silencing suppression were also non-functional in viral cell-to-cell movement. However, we identified mutant P25 proteins that were functional as silencing suppressors but not as movement proteins and we conclude that suppression of silencing is not sufficient to allow virus movement between cells: there must be a second P25 function that is independent of silencing but also required for cell-to-cell movement. Consistent with this hypothesis, we identified two classes of suppressor-inactive P25 mutants. One class of these mutants is proposed to be functional for the accessory function because their failure to support PVX movement could be complemented by heterologous suppressors of silencing. The second class of P25 mutants is considered defective for both the suppressor and second functions because the heterologous silencing suppressors did not restore virus movement. It is possible, based on analyses of short interfering RNA accumulation, that P25 suppresses silencing by interfering with either assembly or function of the effector complexes of RNA silencing. 相似文献
64.
Embrey MW Wai JS Funk TW Homnick CF Perlow DS Young SD Vacca JP Hazuda DJ Felock PJ Stillmock KA Witmer MV Moyer G Schleif WA Gabryelski LJ Jin L Chen IW Ellis JD Wong BK Lin JH Leonard YM Tsou NN Zhuang L 《Bioorganic & medicinal chemistry letters》2005,15(20):4550-4554
Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide 1 led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC(95) of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs. 相似文献
65.
Cainelli G Galletti P Garbisa S Giacomini D Sartor L Quintavalla A 《Bioorganic & medicinal chemistry》2005,13(22):6120-6132
A series of compounds combining the beta-lactam and polyphenol scaffold have been prepared and evaluated for inhibition of human leukocyte elastase and matrix metallo-proteases MMP-2 and MMP-9. The design of these compounds has been based on the 'overlapping-type' strategy where two pharmacophores are linked in a single molecule. The most powerful compound against elastase was an N-galloyl-4-alkyliden beta-lactam, [3-[1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-4-oxo-1-(3,4,5-tris-benzyloxy-benzoyl)-azetidin-2-ylidene]-acetic acid ethylester, with an IC50 of 0.5 microM; while the most powerful against MMP-2 was a 4-alkyliden beta-lactam arylated on the C-3 hydroxy side chain (3,5-bis-benzyloxy-4-hydroxy-benzoic acid 1-(2-benzyloxycarbonylmethylene-4-oxo-azetidin-3-yl)-ethyl ester) with an IC50 of 4 microM. Of the total 35 compounds tested, high levels of inhibition of elastase and of MMPs were separately exerted by distinct molecules. 相似文献
66.
Pietrak BL Crouthamel MC Tugusheva K Lineberger JE Xu M DiMuzio JM Steele T Espeseth AS Stachel SJ Coburn CA Graham SL Vacca JP Shi XP Simon AJ Hazuda DJ Lai MT 《Analytical biochemistry》2005,342(1):144-151
The deposition of beta-amyloid peptides (A beta42 and A beta40) in neuritic plaques is one of the hallmarks of Alzheimer's disease (AD). A beta peptides are derived from sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretases. BACE-1 has been shown to be the major beta-secretase and is a primary therapeutic target for AD. In this article, two novel assays for the characterization of BACE-1 inhibitors are reported. The first is a sensitive 96-well HPLC biochemical assay that uses a unique substrate containing an optimized peptide cleavage sequence, NFEV, spanning from the P2-P2' positions This substrate was processed by BACE-1 approximately 10 times more efficiently than was the widely used substrate containing the Swedish (NLDA) sequence. As a result, the concentration of the enzyme required for the assay can be as low as 100 pM, permitting the evaluation of inhibitors with subnanomolar potency. The assay has also been applied to related aspartyl proteases such as cathepsin D (Cat D) and BACE-2. The second assay is a homogeneous electrochemiluminescence assay for the evaluation of BACE-1 inhibition in cultured cells that assesses the level of secreted amyloid EV40_NF from HEK293T cells stably transfected with APP containing the novel NFEV sequence. To illustrate the use of these assays, the properties of a potent, cell-active BACE-1 inhibitor are described. 相似文献
67.
68.
Morphological investigations of morphogenesis accompanying the metamorphosis of the cinctoblastula larva of poriferan Plakina trilopha (Homoscleromorpha) have been made. The larva possesses a distinct columnar epithelium which subdivides into three cellular areas: antero-lateral, postero-lateral, and posterior one. Characteristic morphological features of the cells in each area can be used as natural markers when tracing the fate of larval cells during metamorphosis. The ciliated epithelium of the larva is transformed directly into choanoderm and pinacoderm, without losing its organization. This transformation is a peculiar feature of the metamorphosis in Homoscleromorpha. Metamorphosis in P. trilopha is based on epithelial morphogenesis and includes the mechanisms of flattening of the exopinacoderm, evagination and invagination of larval epithelium in the course of the development of the rhagon aquiferous system. The flattening of larval cells during exopinacoderm formation in metamorphosing P. trilopha is a common change of cell shape during epithelial morphogenesis of this species. The separation of proximal fragments of cells has been observed here. This phenomenon, that we have called “cytoplasmic shedding”, appears to play an important role in the change of epithelial cell shape in P. trilopha. Mechanism of epithelial–mesenchymal transition, i.e., ingression of epithelial ciliated cells into the cavity of the metamorphosing larva of P. trilopha participates in mesohylar cell origin. 相似文献
69.
Hua-Poo Su Youwei Yan G. Sridhar Prasad Robert F. Smith Christopher L. Daniels Pravien D. Abeywickrema John C. Reid H. Marie Loughran Maria Kornienko Sujata Sharma Jay A. Grobler Bei Xu Vinod Sardana Timothy J. Allison Peter D. Williams Paul L. Darke Daria J. Hazuda Sanjeev Munshi 《Journal of virology》2010,84(15):7625-7633
70.
Kukulska A Krajewska J Roskosz J Handkiewicz-Junak D Jarzab M Paliczka E Puch Z Wygoda Z Gubała E Jarzab B 《Endokrynologia Polska》2006,57(4):374-379
INTRODUCTION: The aim of this study was to compare the early outcomes between two groups of patients with differentiated thyroid carcinoma (DTC) who received 60 or 100 mCi of (131)I for remnant ablation. MATERIAL AND METHODS: 224 DTC patients with primary tumor > 1 cm of diameter or multifocal were randomised into prospective clinical trial. Patients with extrathyroideal extension of primary tumor and nodal metastases or M1 were not enrolled. 99 patients received 60 mCi, and 125--100 mCi of radioiodine as the first ablative dose. RESULTS: The effectiveness of thyroid ablation was evaluated after one year, during endogenous TSH (thyroid stimulating hormone) stimulation, and after two years during Lthyroxine therapy. Whole body scintigraphy (WBS) was performed under thyroxine withdrawal and thyroglobulin serum level was assessed. Distant micrometastases were detected in 9.8% of patients by post-therapy WBS, 11 patients in group A treated with 60 mCi and 11 in group B treated with 100 mCi. In other patients no symptoms of persistent disease were detected. At one year follow up full remission was diagnosed in 176 patients: 76 in group A and 100 in group B. The remaining ones, 13.3% and 11.2% respectively, received the second course of (131)I for remnant ablation. There were no statistically significant differences in Tg (thyroglobulin) serum level either 12 or 24 months after 131I treatment. CONCLUSIONS: Our evaluation of early efficacy of adjuvant radioiodine treatment in low risk DTC patients shows no differences between two radioiodine activities - 60 and 100 mCi in relation to thyroid ablation. Thus, the activity of 60 mCi is recommended. 相似文献