11,636 research outputs found

    Thyroid hormone and glucocorticoid independently regulate the expression of estrogen receptor in male Xenopus liver cells.

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    Earlier studies from our laboratory had shown that triiodothyronine (T-3) strongly potentiates the activation by estradiol (E(2)) of silent vitellogenin (Vit) genes and the autoinduction of estrogen receptor (ER) mRNA in primary cultures of male Xenopus hepatocytes (Rabelo and Tata, 1993). It was, however, not known if T-3, or other hormones, could up-regulate ER mRNA in the absence of exogenous E(2). We now show that T-3 and dexamethasone (Dex), but not progesterone and testosterone, directly induce ER mRNA within 4 h by separate pathways, at doses compatible with the K-d values of their receptors. This induction of ER mRNA is accompanied by a marked enhancement of the activation of the silent Vit B1 gene if E(2) is added by 12 h after T-3 and Dex, thus suggesting an elevated level of functional ER induced by the two hormones. This conclusion was supported by a higher rate of transcription from an estrogen response element (ERE)-tk-CAT construct transfected into cultured hepatocytes pre-treated with T-3 and Dex before incubation with estrogen. Our findings emphasize the importance of hormonal interplay via auto- and cross-regulation of nuclear hormone receptors

    Letter from T.H. Hayes, Jr. to Attorney Henry M. Beaty Jr

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    A letter of recommendation for Russell B. Sugarmon, Jr. to be admitted to the bar in Memphis and Shelby County. The author commends his ability, character, and family background

    Dominant-negative mutant thyroid hormone receptors prevent transcription from Xenopus thyroid hormone receptor beta gene promoter in response to thyroid hormone in Xenopus tadpoles in vivo

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    We describe a dominant-negative approach in vivo to assess the strong, early upregulation of thyroid hormone receptor beta (TR beta) gene in response to thyroid hormone, characteristic of the onset of natural and thyroid hormone-induced amphibian metamorphosis, 3,3',5-Triiodothyronine (T-3) treatment of organ cultures of premetamorphic Xenopus tadpole tails coinjected in vivo with the wild-type Xenopus TR beta (wt-xTR beta) and three different thyroid responsive element chloramphenicol acetyltransferase (TRE-CAT) reporter constructs, including a direct repeat +4 (DR +4) element in the -200/+87 fragment of the xTR beta promoter, resulted in a 4- to 8-fold enhancement of CAT activity, Two human C-terminal TR beta 1 mutants (Delta-hTR beta 1 and fs-hTR beta 1), an artificial Xenopus C-terminal deletion mutant (mt-xTR beta), and the oncogenic viral homolog v-erbA none of which binds T-3, inhibited this T-3 response of the endogenous wt-xTR in Xenopus XTC-2 cells cotransfected with the -1600/+87 xTR beta promoter-CAT construct, the potency of the dominant-negative effect of these mutant TRs being a function of the strength of their heterodimerization with Xenopus retinoid X receptor gamma, Coinjection of the dominant-negative Xenopus and human mutant TR beta s into Xenopus tadpole tails totally abolished the T-3 responsiveness of the wt-xTR beta with different TREs, including the natural DR +4 TRE of the xTR beta promoter

    A Small Trinucleotide Expansion in the TBP Gene Gives Rise to a Sporadic Case of SCA17 with Abnormal Putaminal Findings on MRI

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    A Japanese woman developed gait disturbances at 25 years of age, and subsequently underwent gradual changes in her personality. By the age of 42, she showed clear signs of dementia and cerebellar ataxia, and displayed behavioral abnormalities, choreic movements and hyperreflexia. The findings of MRI not only showed cerebellar and cerebral atrophy, but also revealed putaminal rim hyperintensity on T2-weighted images. We identified a heterozygously expanded CAG/CAA repeat (45/36) within the TATA-binding protein gene, leading to a diagnosis of SCA17. These results show that a 45 CAG/CAA repeat is pathological, giving rise to early-onset SCA17.</p

    A structural investigation of bacterial twin-arginine translocation (tat) complexes by single-particle electron microscopy

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    The Twin arginine translocase (Tat) pathway was first characterised in chloroplast thylakoid membranes in the late 1990s. It has since been identified in the plasma membranes of both Gram-positive and Gram-negative bacteria. Substrates of this transport system contain a critical twin-arginine motif within their cleavable Nterminal signal sequence and the majority are large co-factor containing proteins. There is now considerable evidence that Tat systems can transport such globular proteins in a fully folded state. The minimal components required for transport in E.coli are TatA, TatB and TatC; these three integral membrane proteins are thought to form an active translocon. In Bacillus subtilis only TatA and TatC subunits are present, with TatA acting in a bifunctional manner to replace TatB. Little structural information is known about these multimeric integral membrane protein complexes due to the inherent difficulty in purifying them and their compositional variability. Complexes formed by B. subtilis TatAd and TatAyCy and E. coli TatE were investigated by single-particle EM analysis. An image processing protocol was developed to analyse and separate out individual Tat complexes based on their size. Using this method 3D electron density maps were generated of TatAd and TatE, which appear as small, ring-shaped complexes. Unlike E. coli TatA complexes, that have been shown to vary widely in size, those observed here appear small and homogeneous. These data conflict with the widely accepted ‘size-fitting pore’ model of Tat mediated translocation and rather support the alternative transient coalescent model. Additionally the first structural characterisation of a TatA-type mutant protein was performed revealing a dramatic polymerisation phenotype and indicating a primary role for the N-terminus in forming protein-protein interactions
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