RESUMO
The extra sex combs (esc) gene of Drosophila and its mammalian homologue embryonic ectoderm development (eed) play pivotal roles in establishing Polycomb-group (Pc-G) mediated transcriptional silencing of regulatory genes during early development. We have carried out a two-hybrid screen in yeast to identify maternally expressed proteins that interact directly with the product of the Xenopus eed homologue, Xeed. Xeed-interacting proteins that were recovered in this screen included a maternal Xenopus histone deacetylase (HDACm), the Xeed protein itself, and a Xenopus homologue of Enhancer of zeste (XEZ) - a second member of the Pc-G that is closely related by sequence similarity to histone methyltransferases. We have also identified a novel interaction between Xeed and a component of the Xenopus basal transcription machinery, TAF(II)32. We show for the first time that each of these proteins interacts with the Xeed polypeptide, both in the yeast two-hybrid assay and in vitro using purified recombinant proteins. XEZ, HDACm and TAF(II)32 mRNAs are all strongly co-expressed with Xeed mRNA in the fertilized egg, further suggesting that their encoded proteins could interact with Xeed during early embryonic development. Our observations support a multi-step model for the onset of transcriptional silencing in which Xeed binds to and inhibits the function of the transcription initiation complex and also recruits proteins that mediate the acquisition by associated chromatin of epigenetically heritable, post-translational modifications.
Assuntos
Proteínas Repressoras/metabolismo , Fatores Associados à Proteína de Ligação a TATA , Fator de Transcrição TFIID , Proteínas de Xenopus , Xenopus laevis/metabolismo , Sequência de Aminoácidos , Animais , Northern Blotting , DNA Complementar/genética , DNA Complementar/isolamento & purificação , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário , Proteína Potenciadora do Homólogo 2 de Zeste , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Dados de Sequência Molecular , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Complexo Repressor Polycomb 2 , Proteínas do Grupo Polycomb , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Repressoras/genética , Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos , Fatores de Transcrição TFII/genética , Fatores de Transcrição TFII/metabolismo , Técnicas do Sistema de Duplo-Híbrido , Xenopus laevis/genéticaRESUMO
Australia will implement a personally controlled electronic health record (PCEHR) over the next three to five years. Development of an e-health policy framework to support this initiative has involved healthcare providers and patients, but the discussion appears to have bypassed non-patient citizens. There is a risk that this omission may result in difficulties with implementation and uptake of the new system.
RESUMO
This paper investigates the coding of dementia in the episode of care in a pilot study group (N=48) post hospital discharge and the possible implications of under-coding. The assigned ICD-10-AM codes and Diagnosis Related Groups were reviewed. Results demonstrate under-coding of dementia and of cognitive deficits; poor correlation between admission diagnoses and dementia codes on separation; and changes in individual patients' cognitive status across forms and assessments in the same admission. The complexities of accurately coding dementias will impact upon planning for future treatments and service provision and will have a flow-on effect for patients, hospitals, and patient care in Australia.
Assuntos
Codificação Clínica/normas , Demência/classificação , Idoso , Idoso de 80 Anos ou mais , Austrália , Grupos Diagnósticos Relacionados , Cuidado Periódico , Feminino , Hospitais/normas , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Retrospectivos , Estados UnidosRESUMO
The small heat shock protein Hsp27 has been shown to be involved in a diverse array of cellular processes, including cellular stress response, protein chaperone activity, regulation of cellular glutathione levels, apoptotic signaling, and regulation of actin polymerization and stability. Furthermore, mutation within Hsp27 has been associated with the human congenital neuropathy Charcot-Marie Tooth (CMT) disease. Hsp27 is known to be expressed in developing embryonic tissues; however, little has been done to determine the endogenous requirement for Hsp27 in developing embryos. In this study, we show that depletion of XHSP27 protein results in a failure of cardiac progenitor fusion resulting in cardia bifida. Furthermore, we demonstrate a concomitant disorganization of actin filament organization and defects in myofibril assembly. Moreover, these defects are not associated with alterations in specification or differentiation. We have thus demonstrated a critical requirement for XHSP27 in developing cardiac and skeletal muscle tissues.