6 research outputs found
Hybrid capture II and PapilloCheck® tests for detection of anal high-risk human papillomavirus
Introduction: This study evaluated the level of concordance between hybrid capture II (HCII) and PapilloCheck® for the detection of high-risk human papillomavirus (HPV) in anal samples. Methods: Anal cell samples collected from 42 human immunodeficiency virus (HIV)+ patients were analyzed. Results: Considering only the 13 high-risk HPV types that are detectable by both tests, HCII was positive for 52.3% of the samples, and PapilloCheck® was positive for 52.3%. The level of concordance was 80.9% (Kappa = 0.61). Conclusions: Good concordance was observed between the tests for the detection of high-risk HPV
Thyroid hormone response element organization dictates the composition of active receptor
Thyroid hormone (triiodothyronine, T3) is known to activate transcription by binding heterodimers of thyroid hormone receptors (TRs) and retinoid X receptors (RXRs). RXR-TRs bind to T3 response elements (TREs) composed of direct repeats of the sequence AGGTCA spaced by four nucleotides (DR-4). In other TREs, however, the half-sites can be arranged as inverted palindromes and palindromes (Pal). Here we show that TR homodimers and monomers activate transcription from representative TREs with alternate half-site placements. TRβ activates transcription more efficiently than TRα at an inverted palindrome (F2), and this correlates with preferential TRβ homodimer formation at F2 in vitro. Furthermore, reconstruction of TR transcription complexes in yeast indicates that TRβ homodimers are active at F2, whereas RXR-TRs are active at DR-4 and Pal. Finally, analysis of TRβ mutations that block homodimer and/or heterodimer formation reveal TRE-selective requirements for these surfaces in mammalian cells, which suggest that TRβ homodimers are active at F2, RXR-TRs at DR-4, and TR monomers at Pal. TRβ requires higher levels of hormone for activation at F2 than other TREs, and this differential effect is abolished by a dimer surface mutation suggesting that it is related to composition of the TR·TRE complex. We propose that interactions of particular TR oligomers with different elements play unappreciated roles in TRE-selective actions of liganded TRs in vivo
Molecular mechanism of thyroid hormone action
Os hormônios tireoideanos (HTs) são necessários para a diferenciação, crescimento e metabolismo de diversos tecidos de vertebrados. Seus efeitos são mediados pelos receptores do hormônio tireoideano (TRs), membros da superfamÃlia dos receptores nucleares. Estes receptores são fatores de transcrição modulares que se ligam em seqüências especÃficas do DNA denominadas elementos responsivos ao TR, que são encontrados nos promotores dos genes regulados pelo HT. Os TRs são codificados
por dois genes distintos, a e b, localizados nos cromossomos 17 e 3, respectivamente. Estas isoformas apresentam diferentes funções e sua expressão é especÃfica para cada tecido. O TR se liga ao DNA como
monômero, homodÃmero ou heterodÃmero com o receptor de retinóide X (RXR). Além disso, o TR modula a atividade transcricional (repressão ou ativação) através da interação com correpressores e co-ativadores, na
ausência e na presença do T3, respectivamente. A compreensão do
mecanismo molecular da ação do receptor do hormônio tireoideano e a definição de sua estrutura cristalográfica contribuirão para a
aquisição de novos conceitos envolvidos na transcrição e nos distúrbios hormonais presentes nas doenças endócrinas, assim como facilitará o desenho de novas drogas, agonistas ou antagonistas, com grande valor
terapêutico.Thyroid hormones (TH) are involved in normal differentiation, growth, and metabolism in several tissues of all vertebrates. Their actions are mediated by the TH receptors (TRs), members of the nuclear hormone receptor superfamily. These receptors are transcription factors that bind to DNA on
specific sequences, the TR response element (TREs), in promoters of target genes. Two genes encode TRs, a e b, located in chromosomes 17 and 3, respectively. These isoforms show different functions and exhibit a tissue specific expression. TRs function as monomers, homodimers or heterodimers with retinoid X receptor (RXR) and modulate transcription activity (repression or activation) by interacting with co-repressor and coactivators,
which associate with TR in the absence or presence of T3, respectively. Understanding the molecular mechanism of TR action and
the definition of its crystallographic structure will provide new insights into
transcription mechanisms and will facilitate the design of new drugs with greater therapeutic value