RESUMO
Expression of the Bacillus subtilis hut operon is subject to regulation by catabolite repression. A set of hut-lacZ transcriptional fusions was constructed and used to identify two cis-acting sites involved in catabolite repression. The hutOCR1 operator site lies immediately downstream of the hut promoter and weakly regulates hut expression in response to catabolite repression. The downstream hutOCR2 operator site lies within the hutP gene, between positions +203 and +216, and is required for wild-type levels of catabolite repression. Both the hutOCR1 and hutOCR2 operators have sequence similarity to the sites which mediate catabolite repression of several other B. subtilis genes. Two mutations which relieve catabolite repression of hut expression were found to alter the nucleotide sequence of the hutOCR2 operator. Catabolite repression of hut expression was partially relieved in strains containing the ccpA mutation but not in strains containing either the pai or hpr mutation.
Assuntos
Aldose-Cetose Isomerases , Bacillus subtilis/genética , Proteínas de Bactérias , Repressão Enzimática , Regulação Bacteriana da Expressão Gênica , Histidina/metabolismo , Óperon/genética , Sequências Reguladoras de Ácido Nucleico/genética , Sequência de Aminoácidos , Sequência de Bases , Biodegradação Ambiental , Carboidratos Epimerases/genética , Análise Mutacional de DNA , Proteínas de Ligação a DNA/genética , Histidina Amônia-Liase/biossíntese , Indol-3-Glicerolfosfato Sintase/genética , Óperon Lac , Dados de Sequência Molecular , Complexos Multienzimáticos/genética , Regiões Operadoras Genéticas/genética , Sistema Fosfotransferase de Açúcar do Fosfoenolpiruvato/genética , Mutação Puntual , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Repressoras/genética , Transcrição GênicaRESUMO
The rate of disease progression was assessed for 42 persons affected by Huntington's disease who had been neurologically examined at least six times and followed up for at least 3 years. Disease progression was assessed by a disability rating scale administered at each examination. Slow progression was associated with older age at onset of disease and with heavier weight (body mass index) at the first examination. Men tended to have a slower disease progression than did women, and this was particularly evident among men inheriting Huntington's disease from affected mothers. Neither the butyrophenone haloperidol nor the tricyclic antidepressant imipramine were related to rate of progression. Assessments of depression, hostility, and tobacco use were also unrelated to rate of progression. Clinical trials in Huntington's disease should consider these factors when designing therapeutic studies.
