RESUMO
AIMS/HYPOTHESIS: To determine the impact of maternal diabetes during pregnancy on racial disparities in fetal growth. METHODS: Using linked birth certificate, inpatient hospital and prenatal claims data we examined live singleton births of mothers resident in South Carolina who self-reported their race as non-Hispanic white (NHW; n = 140,128) or non-Hispanic black (NHB; n = 82,492) and delivered at 28-42 weeks' gestation between 2004 and 2008. RESULTS: Prepregnancy diabetes prevalence was higher in NHB (3.0%) than in NHW (1.7%), while the prevalence of gestational diabetes mellitus (GDM) was similar in NHB (6.1%) and NHW (6.3%). At a delivery BMI of 35 kg/m(2), GDM exposure was associated with an average birthweight only 17 g (95% CI 4, 30) higher in NHW, but 78 g (95% CI 61, 95) higher in NHB (controlling for gestational age, maternal age, infant sex and availability of information on prenatal care). Figures for prepregnancy diabetes were 58 g (95% CI 34, 81) in NHW and 60 g (95% CI 37, 84) in NHB. GDM had a greater impact on birthweight in NHB than in NHW (60 g racial difference [95% CI 39, 82]), while prepregnancy diabetes had a large but similar impact. Similarly, the RR for GDM of having a large- relative to a normal-weight-for-gestational-age infant was lower in NHW (RR 1.41 [95% CI 1.34, 1.49]) than in NHB (RR 2.24 [95% CI 2.05, 2.46]). CONCLUSIONS/INTERPRETATION: These data suggest that the negative effects of GDM combined with obesity during pregnancy may be greater in NHB than in NHW individuals.
Assuntos
Peso ao Nascer/fisiologia , Negro ou Afro-Americano , Diabetes Mellitus Tipo 2/etnologia , Diabetes Gestacional/etnologia , Gravidez em Diabéticas/etnologia , População Branca , Adolescente , Adulto , Feminino , Disparidades nos Níveis de Saúde , Humanos , Recém-Nascido , Masculino , Idade Materna , Obesidade/etnologia , Gravidez , South CarolinaRESUMO
Somatostatin analogues (SAs) are potential anticancer agents. This study was designed to investigate the expression of somatostatin receptors (SSTRs) in melanoma cells and the effect of two SAs on cell proliferation and viability. Eighteen primary and metastatic human cutaneous melanoma cell lines were treated with octreotide and SOM230. Expression of SSTR1, SSTR2, SSTR3 and SSTR5 was assessed by real-time polymerase chain reaction. Proliferation, viability and cell death were assessed using standard assays. Inhibition was modelled by mixed-effect regression. Melanoma cells expressed one or more SSTR. Both SAs inhibited proliferation of most melanoma cell lines, but inhibition was < 50%. Neither SA affected cell viability or induced cell death. The results suggest that melanoma cell lines express SSTRs. The SAs investigated, under the conditions used in this study, did not, however, significantly inhibit melanoma growth or induce cell death. Novel SAs, combination therapy with SAs and their anti-angiogenic properties should be further investigated.
Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma/genética , Melanoma/patologia , Octreotida/farmacologia , Receptores de Somatostatina/genética , Somatostatina/análogos & derivados , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Receptores de Somatostatina/metabolismo , Somatostatina/farmacologiaRESUMO
The walls of Aspergillus nidulans conidia contain a green pigment that protects the spores from damage by ultraviolet light. At least two genes, wA and yA, are required for pigment synthesis: yA mutants produce yellow spores, wA mutants produce white spores, and wA mutations are epistatic to yA mutations. We cloned wA by genetic complementation of the wA3 mutation with a cosmid library containing nuclear DNA inserts from the wild-type strain. The wA locus was mapped to an 8.5-10.5-kilobase region by gene disruption analysis. DNA fragments from this region hybridized to a 7500 nucleotide polyadenylated transcript that is absent from hyphae and mature conidia but accumulates during conidiation beginning when pigmented spores first appear. Mutations in the developmental regulatory loci brlA, abaA, wetA and apsA prevent wA mRNA accumulation. By contrast, yA mRNA fails to accumulate only in the brlA- and apsA- mutants. Thus, the level of wA transcript is regulated during conidiophore development and wA activation requires genes within the central pathway regulating conidiation.
Assuntos
Aspergillus nidulans/genética , Genes Fúngicos , Pigmentos Biológicos/genética , Aspergillus nidulans/crescimento & desenvolvimento , Clonagem Molecular , Cosmídeos , Regulação Fúngica da Expressão Gênica , Teste de Complementação Genética , Mutação , Pigmentos Biológicos/biossíntese , Mapeamento por Restrição , Esporos Fúngicos/genética , Esporos Fúngicos/fisiologia , Transcrição GênicaRESUMO
Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth in which it alternates between a budding haploid saprophyte and a filamentous dikaryotic pathogen. We are interested in identifying the genetic determinants of filamentous growth and pathogenicity in U. maydis. To do this we have taken a forward genetic approach. Earlier, we showed that haploid adenylate cyclase (uac1) mutants display a constitutively filamentous phenotype. Mutagenesis of a uac1 disruption strain allowed the isolation of a large number of budding suppressor mutants. These mutants are named ubc, for Ustilago bypass of cyclase, as they no longer require the production of cyclic AMP (cAMP) to grow in the budding morphology. Complementation of a subset of these suppressor mutants led to the identification of the ubc4 and ubc5 genes, which are required for filamentous growth and encode a MAP (mitogen-activated protein) kinase kinase kinase and a MAP kinase kinase, respectively. Evidence suggests that they are important in the pheromone response pathway and in pathogenicity. These results further support an important interplay of the cAMP and MAP kinase signal transduction pathways in the control of morphogenesis and pathogenicity in U. maydis.
Assuntos
MAP Quinase Quinase Quinases/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/química , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Ustilago/enzimologia , Ustilago/genética , Sequência de Aminoácidos , Proteínas Fúngicas , MAP Quinase Quinase Quinases/química , Dados de Sequência Molecular , Doenças das Plantas/microbiologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Ustilago/crescimento & desenvolvimento , Zea mays/microbiologiaRESUMO
The field of cardiovascular regenerative medicine has made significant strides over the past decade. Clinical trials have demonstrated benefit in acute myocardial infarction (AMI) and chronic heart failure (CHF). As the field has matured, it has defined novel biology and invented an array of therapeutic strategies that are currently under development. In this brief review, we attempt to conceptualize the knowledge to date as well as examine how this knowledge has been translated to various therapeutic strategies.
Assuntos
Infarto do Miocárdio/cirurgia , Regeneração/fisiologia , Medicina Regenerativa/tendências , Transplante de Células-Tronco/tendências , Animais , Ensaios Clínicos como Assunto/tendências , Humanos , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologiaRESUMO
The Aspergillus nidulans wA gene is required for synthesis of a green pigment present in the walls of mature asexual spores (conidia); wA mutants produce colorless (white) conidia. We determined the transcriptional structure and DNA sequence of the wA gene. wA consists of 5 exons separated by short (40-60 bp) introns. The processed transcript has the potential to encode a protein consisting of 1986 amino acid residues. The predicted WA polypeptide showed extensive sequence similarities with bacterial and fungal polyketide synthases and vertebrate fatty acid synthases, particularly within conserved active sites. Properties of the yellow conidial wall pigment intermediate suggest that it is a polyketide rather than a fatty acid. It is therefore likely that wA encodes all or part of a polyketide synthase involved in the formation of this pigment intermediate.
Assuntos
Aspergillus nidulans/genética , Ácido Graxo Sintases/genética , Proteínas Fúngicas/genética , Genes Fúngicos , Complexos Multienzimáticos/genética , Sequência de Aminoácidos , Aspergillus nidulans/fisiologia , Sequência de Bases , DNA Fúngico/genética , Dados de Sequência Molecular , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , Software , Esporos Fúngicos/fisiologia , Transcrição GênicaRESUMO
The Basidiomycete fungus Ustilago maydis causes corn smut disease and alternates between a budding haploid saprophyte and a filamentous dikaryotic pathogen. Previous work demonstrated that haploid adenylate cyclase (uac1) mutants display a constitutively filamentous phenotype. Suppressor mutants of a uac1 disruption strain, named ubc for Ustilago bypass of cyclase, no longer require cAMP for the budding morphology. The ubc2 gene was isolated by complementation and is required for filamentous growth. The deduced amino acid sequence encoded by ubc2 shows localized homology to Sterile Alpha Motif (SAM), Ras Association (RA) and Src homology 3 (SH3) protein-protein interaction domains. A K78E missense mutation within the SAM domain, revealed a genetic interaction between ubc2 and ubc4, a pheromone-responsive MAP kinase kinase kinase. This indicates involvement of ubc2 in the pheromone-responsive MAP kinase cascade and ubc2 is required for pheromone-responsive morphogenesis. The ubc2 gene is a critical virulence factor. Thus, ubc2 encodes a putative novel adaptor protein that may act directly upstream of the pheromone-responsive MAP kinase cascade in U. maydis.
Assuntos
Proteínas Fúngicas/genética , Genes Fúngicos , Ustilago/genética , Proteínas Adaptadoras de Transdução de Sinal , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Primers do DNA/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/fisiologia , Deleção de Genes , Teste de Complementação Genética , Proteínas Quinases Ativadas por Mitógeno/genética , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Fenótipo , Feromônios/farmacologia , Doenças das Plantas/microbiologia , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Temperatura , Ustilago/crescimento & desenvolvimento , Ustilago/patogenicidade , Ustilago/fisiologia , Virulência/genética , Zea mays/microbiologiaRESUMO
Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth in which it alternates between a budding haploid saprophyte and a filamentous dikaryotic pathogen. We are interested in identifying the genetic determinants of filamentous growth and pathogenicity in U. maydis. To do this, we have taken a forward genetic approach. Previously, we showed that haploid adenylate cyclase (uac1) mutants display a constitutively filamentous phenotype. Mutagenesis of a uac1 disruption strain allowed the isolation of a large number of budding suppressor mutants. These mutants are named ubc, for Ustilago bypass of cyclase, as they no longer require the production of cAMP to grow in the budding morphology. Complementation of one of these suppressor mutants led to the identification of ubc3, which is required for filamentous growth and encodes a MAP kinase most similar to those of the yeast pheromone response pathway. In addition to filamentous growth, the ubc3 gene is required for pheromone response and for full virulence. Mutations in the earlier identified fuz7 MAP kinase kinase also suppress the filamentous phenotype of the uac1 disruption mutant, adding evidence that both ubc3 and fuz7 are members of this same MAP kinase cascade. These results support an important interplay of the cAMP and MAP kinase signal transduction pathways in the control of morphogenesis and pathogenicity in U. maydis.
Assuntos
Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ustilago/crescimento & desenvolvimento , Ustilago/patogenicidade , Sequência de Aminoácidos , Clonagem Molecular , Deleção de Genes , Genes Fúngicos , Proteínas Quinases Ativadas por Mitógeno/química , Dados de Sequência Molecular , Feromônios/metabolismo , Doenças das Plantas/microbiologia , Alinhamento de Sequência , Análise de Sequência de DNA , Ustilago/enzimologia , Ustilago/genética , Virulência , Zea mays/microbiologiaRESUMO
Cryptococcus neoformans is a major opportunistic fungal pathogen in AIDS and other immunosuppressed patients. We have shown that wild-type haploid C. neoformans can develop an extensive hyphal phase under appropriate conditions. Hyphae produced under these conditions are monokaryotic, possess unfused clamp connections, and develop basidia with viable basidiospores. The ability to undergo this transition is determined by the presence of the alpha-mating type locus and is independent of serotype. The association of the hyphal phase with the alpha-mating type may explain the preponderance of this mating type in the environment and the nature of the infectious propagule of C. neoformans.
Assuntos
Cryptococcus neoformans/fisiologia , Biossíntese Peptídica , Peptídeos , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Cruzamentos Genéticos , Criptococose , Cryptococcus neoformans/genética , Cryptococcus neoformans/patogenicidade , Haploidia , Humanos , Fator de Acasalamento , Fenótipo , Feromônios , Esporos FúngicosRESUMO
In the plant, filamentous growth is required for pathogenicity of the corn smut pathogen Ustilago maydis. Earlier, we identified a role for the cAMP signal transduction pathway in the switch between budding and filamentous growth for this fungus. A gene designated ubc1 (for Ustilago bypass of cyclase) was found to be required for filamentous growth and to encode the regulatory subunit of a cAMP-dependent protein kinase (PKA). Here, we show that ubc1 is important for the virulence of the pathogen. Specifically, ubc1 mutants are able to colonize maize plants and, like the wild-type pathogen, cause localized symptoms in association with the presence of hyphae. However, in contrast to plants infected with wild-type cells that often developed galls from initially chlorotic tissue, plants infected with the ubc1 mutant did not produce galls. These data suggest that PKA regulation is critical for the transition from saprophytic to pathogenic growth and from vegetative to reproductive development. Plate mating assays in which exogenous cAMP was applied suggested that the cAMP and b mating-type morphogenetic pathways may be coordinated.