RESUMO
Natural variation in the absolute and relative size of different parts of the human brain is substantial, with a range that often exceeds a factor of 2. Much of this variation is generated by the cumulative effects of sets of unknown gene variants that modulate the proliferation, growth and death of neurons and glial cells. Discovering and testing the functions of these genes should contribute significantly to our understanding of differences in brain development, behavior and disease susceptibility. We have exploited a large population of genetically well-characterized strains of mice (BXD recombinant inbred strains) to map gene variants that influence the volume of the dorsal striatum (caudate-putamen without nucleus accumbens). We used unbiased methods to estimate volumes bilaterally in a sex-balanced sample taken from the Mouse Brain Library (www.mbl.org). We generated a matched microarray data set to efficiently evaluate candidate genes (www.genenetwork.org). As in humans, volume of the striatum is highly heritable, with greater than twofold differences among strains. We mapped a locus that modulates striatal volume on chromosome (Chr) 6 at 88 +/- 5 Mb. We also uncovered an epistatic interaction between loci on Chr 6 and Chr 17 that modulates striatal volume. Using bioinformatic tools and the corresponding expression database, we have identified positional candidates in these quantitative trait locus intervals.
Assuntos
Corpo Estriado/anatomia & histologia , Variação Genética/genética , Animais , Mapeamento Cromossômico/métodos , Cromossomos de Mamíferos/genética , Biologia Computacional/métodos , Corpo Estriado/citologia , Corpo Estriado/metabolismo , Cruzamentos Genéticos , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Masculino , Camundongos , Camundongos Endogâmicos , Neurogênese/genética , Análise de Sequência com Séries de Oligonucleotídeos , Tamanho do Órgão/genética , Fenótipo , Locos de Características Quantitativas/genética , Especificidade da EspécieRESUMO
Flies (Diptera: Muscidae) that breed in faeces and other organic refuse (filth flies) have been implicated as vectors of pathogenic bacteria including Escherichia coli O157:H7, which cause haemorrhagic colitis in humans, and Campylobacter, which is the principal causative agent of human enteritis. The potential role of filth flies in the epidemiology of these pathogens in the United States was investigated by examining the prevalence of Campylobacter spp. and E. coli O157:H7 from two Arkansas turkey facilities. Polymerase chain reaction was conducted on DNA extractions of individual Musca domestica Linnaeus, Stomoxys calcitrans (Linnaeus), Hydrotaea aenescens (Wiedemann), Adia cinerella Fallen and turkey faecal samples using primers specific for E. coli H7, O157 and Campylobacter spp. Culturing verified that the flies were carrying viable Campylobacter spp. and E. coli O157:H7. Results from this study indicated that M. domestica, S. calcitrans, H. aenescens and Anthomyids are capable of carrying Campylobacter in North American poultry facilities and that the E. coli O157:H7 is carried by house flies and black dump flies associated with poultry. This PCR method provided a rapid and effective method to identify Campylobacter spp. and E. coli O157:H7 directly from individual filth flies.
Assuntos
Campylobacter/genética , Dípteros/microbiologia , Escherichia coli O157/genética , Insetos Vetores/microbiologia , Perus/microbiologia , Animais , Campylobacter/crescimento & desenvolvimento , Bovinos , DNA Bacteriano/química , DNA Bacteriano/genética , Escherichia coli O157/crescimento & desenvolvimento , Fezes/microbiologia , Feminino , Microbiologia de Alimentos , Masculino , Reação em Cadeia da Polimerase , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/transmissão , Análise de Sequência de DNARESUMO
There is increasing evidence that endothelial cells respond to a variety of mediators. In the current studies rat pulmonary artery endothelial cells (RPAEC) responded to human recombinant C5a and tumor necrosis factor-alpha (TNF-alpha) with the generation of superoxide (O2-). RPAEC responsiveness was dependent on whether cells had been obtained from confluent or subconfluent cell monolayers. RPAEC responded to C5a and TNF-alpha in a dose-dependent manner, with increases in intracellular Ca2+ (Cai2+), formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], and generation of O2-. Optimal O2- responses occurred in cells that had been pretreated with the inhibitor of superoxide dismutase (SOD), diethyldithiocarbamate, and O2- responses were allopurinol insensitive. Pertussis toxin pretreatment abolished the ability of C5a to cause increases in Ins(1,4,5)P3 and Cai2+ and formation of O2- but did not inhibit the changes in Cai2+ and formation of O2- after addition of TNF-alpha. The O2- response to C5a but not to TNF-alpha was abolished by pretreatment with the inhibitor of protein kinase C, staurosporine. These data indicate that signal transduction events in response to C5a and TNF-alpha were fundamentally different.
