RESUMO
von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag ≥30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag ≤5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population.
Assuntos
Doença de von Willebrand Tipo 1/sangue , Adolescente , Testes de Coagulação Sanguínea , Hibridização Genômica Comparativa , Feminino , Variação Genética , Hemorragia/etiologia , Humanos , Masculino , Fenótipo , Análise de Sequência de DNA , Inquéritos e Questionários , Estados Unidos/epidemiologia , Adulto Jovem , Doença de von Willebrand Tipo 1/diagnóstico , Doença de von Willebrand Tipo 1/epidemiologia , Fator de von Willebrand/análise , Fator de von Willebrand/genéticaRESUMO
Sexual reproduction in the ciliate Tetrahymena follows a complex developmental program involving the sequential regulation of dozens of genes. Genes that are up-regulated during post-zygotic development in Tetrahymena were isolated by subtractive hybridization. Anlagen stage induced gene 1 (ASI1) encodes a 2.8 kb transcript that contains a single intron and is induced during macronuclear development. ASI1 is a single copy gene in both the micronucleus and the macronucleus. It encodes a 95 kDa conceptual protein with a leucine zipper near the amino terminus.
Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Zíper de Leucina , Proteínas de Protozoários/biossíntese , Proteínas de Protozoários/genética , Regulação para Cima , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Quimiotaxia , Íntrons , Modelos Genéticos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , TetrahymenaRESUMO
MarA47(Yp) from Yersinia pestis, showing 47% identity to Escherichia coli MarA in its N terminus, caused resistance to antibiotics and to organic solvents when expressed in both E. coli and Y. pestis. Resistance was linked to increased expression of the AcrAB multidrug efflux pump. In four of five spontaneous multidrug-resistant mutants of Y. pestis independently selected by growth on tetracycline, the marA47(Yp) gene was overexpressed. The findings suggest that marA47(Yp) is a marA ortholog in Y. pestis.
Assuntos
Proteínas de Ligação a DNA/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/biossíntese , Proteínas de Escherichia coli/genética , Lipoproteínas/biossíntese , Proteínas de Membrana Transportadoras/biossíntese , Yersinia pestis/genética , Sequência de Aminoácidos , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Alinhamento de Sequência , Yersinia pestis/efeitos dos fármacos , Yersinia pestis/isolamento & purificação , Yersinia pestis/metabolismoRESUMO
The ciliated protozoan Tetrahymena has two nuclei: a germ line micronucleus and a somatic macronucleus. The transcriptionally active macronucleus has about 50 copies of each chromosome. At sexual reproduction (conjugation), the parental macronucleus is degraded and new macronucleus develops from a mitotic product of the zygotic micronucleus. Development of the macronucleus involves massive genome remodeling, including deletion of about 6000 specific internal eliminated sequences (IES) and multiple rounds of DNA replication. A gene encoding a putative signal transduction receptor, ASI2, (anlagen stage induced 2) is up-regulated during development of the new macronuclei (anlagen). Macronuclear ASI2 is nonessential for vegetative growth. Homozygous ASI2 germ line knockout cells with wild type parental macronuclei proceed through mating but arrest at late macronuclear anlagen development and die before the first post-conjugation fission. IES elimination occurs in these cells. Two rounds of postzygotic DNA replication occur normally in progeny of ASI2 germ line knockouts, but endoreduplication of the macronuclear genome is arrested. The germ line ASI2 null phenotype is rescued in a mating of a knockout strain with wild type cells.