RESUMO
The Drosophila teashirt (tsh) gene has an homeotic function which, in combination with HOM-C genes, determines thoracic and abdominal (trunk) identities. Analysis of TSH protein distribution during embryogenesis using a specific polyclonal antibody shows that it is nuclear. The protein is present with regional modulation in several tissues within the trunk, suggesting additional tsh functions to those already studied. We identified a candidate tsh target shared with some HOM-C genes, the modifier of variegation gene modulo (mod). The TSH zinc-finger protein recognizes in vitro two specific sites within a 5' control element of the mod gene which responds in vivo to tsh activity. TSH is therefore a DNA binding protein and might directly control mod expression.
Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Drosophila , Genes Homeobox , Hormônios de Inseto/química , Proteínas Repressoras , Fatores de Transcrição/química , Dedos de Zinco , Animais , Sequência de Bases , Drosophila , Ectoderma/metabolismo , Dados de Sequência Molecular , Mapeamento por RestriçãoRESUMO
The maternal-fetal HIV transmission trials, conducted in developing countries in the 1990s, undoubtedly generated one of the most intense, high profile controversies in international research ethics. They sparked off a prolonged acrimonious and public debate and deeply divided the scientific community. They also provided an impetus for the revision of the Declaration of Helsinki--the most widely known guideline for international research. In this paper, I provide a brief summary of the context, outline the arguments for and against the controversial use of placebo controls, and focus on particular areas that I believe merit further discussion or clarification. On balance, I argue that the researchers failed in their duties to protect the best interests of their research subjects, and to promote distributive justice. I discuss the difficulties of obtaining valid consent in this research context, and argue that it is unethical to inform women of their HIV status without at least offering them prophylactic treatment for their unborn children. A global view of justice, which endorses international equity, cannot be squared with international research guidelines that allow 'local conditions' to define the scope of duty to the control group. Finally, I suggest that the heated debate reflects a tension, if not an outright war, between two conflicting meta-ethical systems, or incommensurable paradigms, that underpin scientific research involving human subjects.
Assuntos
Países em Desenvolvimento , Análise Ética , Infecções por HIV/transmissão , Experimentação Humana , Transmissão Vertical de Doenças Infecciosas , Internacionalidade , Placebos , Gestantes , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Projetos de Pesquisa , Ética em Pesquisa , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Declaração de Helsinki , Humanos , Consentimento Livre e Esclarecido , Gravidez , Justiça Social , ZidovudinaRESUMO
Seroprevalence monitoring of HIV in pregnant women by anonymized unlinked testing has been widely adopted in the UK and other countries. The scientific rationale is to eliminate participation and selection bias. The ethical justification is that the public good outweighs any harm to individuals. The assumption has been that individuals have had their autonomy respected by the offer of informed consent. In the light of new scientific evidence, it is doubtful that the public good is best served by the continuation of anonymously testing women receiving antenatal care. It is submitted that it is no longer ethical for health professionals to refrain from informing pregnant women of the benefits of voluntary named testing, or to request their consent to anonymized testing. The legal and moral concept of duty of care is examined, and the abrogation of this duty through anonymization is explained.
Assuntos
Sorodiagnóstico da AIDS/legislação & jurisprudência , Testes Anônimos , Beneficência , Confidencialidade/legislação & jurisprudência , Revelação , Ética Médica , Infecções por HIV/diagnóstico , Testes Obrigatórios/legislação & jurisprudência , Obrigações Morais , Defesa do Paciente/legislação & jurisprudência , Autonomia Pessoal , Complicações Infecciosas na Gravidez/diagnóstico , Gestantes , Diagnóstico Pré-Natal , Medição de Risco , Medicina Baseada em Evidências , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Consentimento Livre e Esclarecido/legislação & jurisprudência , Relações Médico-Paciente , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Cuidado Pré-Natal/legislação & jurisprudência , Alocação de Recursos , Viés de Seleção , Justiça Social , Recusa do Paciente ao Tratamento/legislação & jurisprudência , Reino Unido , Programas VoluntáriosRESUMO
Homeotic genes determine the identities of metameres in Drosophila. We have examined functional aspects of the homeotic gene teashirt by ectopically expressing its product under the control of a heat-shock promoter during embryogenesis. Our results confirm that the gene is critical for segmental identity of the larva. Under mild heat-shock conditions, the Teashirt protein induces an almost complete transformation of the labial to prothoracic segmental identity, when expressed before 8 hours of development. Positive autoregulation of the endogenous teashirt gene and the presence of Sex combs reduced protein in the labium explain this homeosis. Patterns in the maxillary and a more anterior head segment are partly replaced with trunk ones. Additional Teashirt protein has no effect on the identity of the trunk segments where the gene is normally expressed; teashirt function is overridden by some homeotic complex acting in the posterior trunk. Strong heat-shock regimes provoke novel defects: ectopic sense organs differentiate in posterior abdominal segments and trunk pattern elements differentiate in the ninth abdominal segment. Teashirt acts in a partially redundant way with certain homeotic complex proteins but co-operates with them for the establishment of specific segment types. We suggest that Teashirt and HOM-C proteins regulate common sets of downstream target genes.