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1.
New Phytol ; 201(3): 1009-1020, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24180488

RESUMO

Many angiosperm families develop spatially regulated anthocyanin spots on their flowers. The Asiatic hybrid lily (Lilium spp.) cv 'Latvia' develops splatter-type spots on its tepals. The splatters arise simply from the deposition of anthocyanin pigments in the tepal epidermis. To determine how splatter development was regulated, we analysed the transcription of anthocyanin biosynthesis genes, and isolated and characterized an R2R3-MYB gene specific to splatter pigmentation. All anthocyanin biosynthesis genes were expressed in splatter-containing regions of tepals, but not in other regions, indicating that splatter pigmentation is caused by the transcriptional regulation of biosynthesis genes. Previously characterized LhMYB12 regulators were not involved in splatter pigmentation, but, instead, a new allele of the LhMYB12 gene, LhMYB12-Lat, isolated in this study, contributed to splatter development. In 'Latvia' and other lily plants expressing splatters, LhMYB12-Lat was preferentially transcribed in the splatter-containing region of tepals. Progeny segregation analysis showed that LhMYB12-Lat genotype and splatter phenotype were co-segregated among the F1 population, indicating that LhMYB12-Lat determines the presence or absence of splatters. LhMYB12-Lat contributes to splatter development, but not to full-tepal pigmentation and raised spot pigmentation. As a result of its unique sequences and different transcription profiles, this new allele of LhMYB12 should be a novel R2R3-MYB specifically associating with splatter spot development.


Assuntos
Alelos , Flores/anatomia & histologia , Flores/genética , Genes de Plantas/genética , Hibridização Genética , Lilium/genética , Pigmentação , Sequência de Aminoácidos , Antocianinas/biossíntese , Vias Biossintéticas/genética , Segregação de Cromossomos , Cruzamentos Genéticos , Flores/crescimento & desenvolvimento , Regulação da Expressão Gênica de Plantas , Genótipo , Lilium/anatomia & histologia , Dados de Sequência Molecular , Fenótipo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Alinhamento de Sequência , Nicotiana/genética , Transcrição Gênica , Transformação Genética
2.
J Pharm Sci ; 100(9): 3854-61, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21607954

RESUMO

We previously showed that oseltamivir, a prodrug of the influenza virus neuraminidase inhibitor Ro 64-0802, is a substrate of proton-coupled oligopeptide transporter (PEPT1), and its intestinal absorption in rats is markedly inhibited by administration with milk. To investigate the importance of PEPT1 for oseltamivir absorption in humans, and the characteristics of the drug-milk interaction, a crossover clinical study was conducted in healthy volunteers, who received 75 mg of oseltamivir with 400 mL of water or milk. Milk significantly reduced the maximum plasma concentration (C(max) ) and the area under the plasma concentration-time curve from 0 to 2 h (AUC(0-2) ) of both oseltamivir and Ro 64-0802 (oseltamivir, 68.9% and 34.5%; Ro 64-0802, 69.5% and 14.2%, respectively, vs. water), but had no significant effect on the apparent terminal half-life (t(1/2) ) or AUC(0-∞) . Urinary recovery of oseltamivir and Ro 64-0802 was significantly reduced to 77.5% of the control by milk. The early reduction of oseltamivir absorption might be through the PEPT1 inhibition by milk peptides. However, the extent of interaction in humans was limited as compared with that in rats, possibly because of species difference in the PEPT1 expression and its contribution. This might be the first report suggesting the clinical drug-food interaction via PEPT1.


Assuntos
Antivirais/farmacocinética , Leite , Oseltamivir/farmacocinética , Acetamidas/sangue , Acetamidas/farmacocinética , Acetamidas/urina , Adulto , Animais , Antivirais/sangue , Antivirais/urina , Área Sob a Curva , Estudos Cross-Over , Interações Alimento-Droga , Meia-Vida , Humanos , Oseltamivir/sangue , Oseltamivir/urina , Valores de Referência
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