21 research outputs found
Mass Spectrometric Characterization of the Glycosylation Pattern of HIV-gp120 Expressed in CHO Cells
Molecular Origins for the Dominant Negative Function of Human Glucocorticoid Receptor Beta
This study molecularly elucidates the basis for the dominant negative mechanism of the glucocorticoid receptor (GR) isoform hGRβ, whose overexpression is associated with human glucocorticoid resistance. Using a series of truncated hGRα mutants and sequential mutagenesis to generate a series of hGRα/β hybrids, we find that the absence of helix 12 is neither necessary nor sufficient for the GR dominant negative phenotype. Moreover, we have localized the dominant negative activity of hGRβ to two residues and found that nuclear localization, in addition to heterodimerization, is a critical feature of the dominant negative activity. Molecular modeling of wild-type and mutant hGRα and hGRβ provides structural insight and a potential physical explanation for the lack of hormone binding and the dominant negative actions of hGRβ
Structural Determinates for Apolipoprotein E-Derived Peptide Interaction with the α7 Nicotinic Acetylcholine Receptor
Human Glucocorticoid Receptor β Binds RU-486 and Is Transcriptionally Active
Human glucocorticoid receptor (hGR) is expressed as two alternately spliced C-terminal isoforms, α and β. In contrast to the canonical hGRα, hGRβ is a nucleus-localized orphan receptor thought not to bind ligand and not to affect gene transcription other than by acting as a dominant negative to hGRα. Here we used confocal microscopy to examine the cellular localization of transiently expressed fluorescent protein-tagged hGRβ in COS-1 and U-2 OS cells. Surprisingly, yellow fluorescent protein (YFP)-hGRβ was predominantly located in the cytoplasm and translocated to the nucleus following application of the glucocorticoid antagonist RU-486. This effect of RU-486 was confirmed with transiently expressed wild-type hGRβ. Confocal microscopy of coexpressed YFP-hGRβ and cyan fluorescent protein-hGRα in COS-1 cells indicated that the receptors move into the nucleus independently. Using a ligand binding assay, we confirmed that hGRβ bound RU-486 but not the hGRα ligand dexamethasone. Examination of the cellular localization of YFP-hGRβ in response to a series of 57 related compounds indicated that RU-486 is thus far the only identified ligand that interacts with hGRβ. The selective interaction of RU-486 with hGRβ was also supported by molecular modeling and computational docking studies. Interestingly, microarray analysis indicates that hGRβ, expressed in the absence of hGRα, can regulate gene expression and furthermore that occupation of hGRβ with the antagonist RU-486 diminishes that capacity despite the lack of helix 12 in the ligand binding domain
The Production History and Reception of Brian Friel's Dancing at Lughnasa in Irish and Czech contexts
Thesis Abstract The aim of this thesis is to compare the production history and reception of Brian Friel's Dancing at Lughnasa, arguably one of his most famous and successful plays, in Irish and Czech contexts. Following its triumphant premiere at the Abbey Theatre in 1990 directed by Patrick Mason, the production transferred to London and Broadway, where it garnered further critical acclaim and several prestigious awards. The first Czech production, directed by Jan Burian, opened at Divadlo na Vinohradech in Prague in 1993, and over the course of the next twenty years it was staged another eight times on Czech professional - mostly regional stages. The opening chapter of the thesis focuses on the analysis of Dancing at Lughnasa using the method of close reading, as well as consulting secondary literature. The following chapter is divided into two parts, the first of them attempting to outline the background of the play by focusing on the events of the 1930s in Ireland. The second part is concerned with the context of writing Dancing at Lughnasa. Chapters four and five comprise the main body of the thesis and deal with the description of the five most significant productions in Ireland and the Czech Republic. These chapters focus on the context, the directors' concept, the acting and the critical acclaim...
Zika virus homology model of DEXDc
Homology model of DEXDc protein from
<p><b>Illustrating and Homology Modeling
the Proteins of the Zika Virus</b></p