RESUMO
The chemical stage of the Monte Carlo track-structure (MCTS) code Geant4-DNA was extended for its use in DNA strand break (SB) simulations and compared against published experimental data. Geant4-DNA simulations were performed using pUC19 plasmids (2686 base pairs) in a buffered solution of DMSO irradiated by60Co or137Csγ-rays. A comprehensive evaluation of SSB yields was performed considering DMSO, DNA concentration, dose and plasmid supercoiling. The latter was measured using the super helix density value used in a Brownian dynamics plasmid generation algorithm. The Geant4-DNA implementation of the independent reaction times method (IRT), developed to simulate the reaction kinetics of radiochemical species, allowed to score the fraction of supercoiled, relaxed and linearized plasmid fractions as a function of the absorbed dose. The percentage of the number of SB after â¢OH + DNA and H⢠+ DNA reactions, referred as SSB efficiency, obtained using MCTS were 13.77% and 0.74% respectively. This is in reasonable agreement with published values of 12% and 0.8%. The SSB yields as a function of DMSO concentration, DNA concentration and super helix density recreated the expected published experimental behaviors within 5%, one standard deviation. The dose response of SSB and DSB yields agreed with published measurements within 5%, one standard deviation. We demonstrated that the developed extension of IRT in Geant4-DNA, facilitated the reproduction of experimental conditions. Furthermore, its calculations were strongly in agreement with experimental data. These two facts will facilitate the use of this extension in future radiobiological applications, aiding the study of DNA damage mechanisms with a high level of detail.
Assuntos
Dano ao DNA , Dimetil Sulfóxido , Simulação por Computador , DNA/química , Método de Monte Carlo , Conformação de Ácido Nucleico , PlasmídeosRESUMO
Broiler chicks aged 12 h after hatching were allotted according to a block design in a 7 x 2 factorial schedule of 14 treatments and four replications of 50 chicks each one. The main experimental factors were fasting for 0, 6, 12, 18, 24, 30, and 36 h after chick placement and sex. Independent of sex, fasting had a negative linear effect on weight and productivity of broilers at market age (42 d) without affecting feed conversion or mortality index. Groups subjected to 18 and 36 h of fasting after placement, corresponding to 30 and 48 h posthatching fasting, had lower biometrical values for small intestine (length, weight, and size; villus height; and crypt depth) than chicks fed immediately after placement. According to the Pearson test, BW of birds at 21 and 42 d were significantly correlated to BW at 7 d (r=0.77) and 21 d (r=0.45), respectively. Males performed better than females but had higher mortality rates. Fasting did not influence serum concentrations of corticosterone or sexual steroid hormones. Nevertheless, early signs of sexual dimorphism arose from the high estradiol (E2) concentration on female serum. Heterophil:lymphocyte ratio was not different among treatments, indicating that early fasting did not seem to be a stress factor 21 or 42 d after fasting. The results suggested a maximum fasting of 24 h after hatching in order to preserve broiler productivity at market age.
Assuntos
Envelhecimento , Galinhas/fisiologia , Jejum , Animais , Animais Recém-Nascidos , Peso Corporal , Galinhas/crescimento & desenvolvimento , Corticosterona/sangue , Estradiol/sangue , Feminino , Hormônios Esteroides Gonadais/sangue , Intestino Delgado/anatomia & histologia , Contagem de Leucócitos , Masculino , Tamanho do Órgão , Caracteres Sexuais , Saco Vitelino/fisiologiaRESUMO
Fetal abnormalities including chylous ascites, polyhydramnios, claw hands, and hammer toes were identified in an infant who had a missense mutation R106P and a 52bp deletion in the gene for a peroxisomal beta-oxidation enzyme, D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase, D-bifunctional protein. The patient had psychomotor retardation and craniofacial dysmorphism and died at 7 months of age. The patient had atypical fetal manifestations of this enzyme deficiency.
Assuntos
17-Hidroxiesteroide Desidrogenases , 3-Hidroxiacil-CoA Desidrogenases/deficiência , Ascite Quilosa/congênito , Ascite Quilosa/complicações , Contratura/congênito , Contratura/complicações , Enoil-CoA Hidratase , Deformidades Congênitas do Pé/complicações , Deformidades Congênitas da Mão/complicações , Hidroliases/deficiência , Complexos Multienzimáticos/deficiência , Poli-Hidrâmnios/complicações , 3-Hidroxiacil-CoA Desidrogenases/genética , Ascite Quilosa/genética , Contratura/genética , Evolução Fatal , Feminino , Deformidades Congênitas do Pé/genética , Deleção de Genes , Deformidades Congênitas da Mão/genética , Humanos , Hidroliases/genética , Lactente , Recém-Nascido , Masculino , Complexos Multienzimáticos/genética , Mutação de Sentido Incorreto/genética , Proteína Multifuncional do Peroxissomo-2 , GravidezRESUMO
We report 2 patients with atypical glycogen storage disease type Ib without neutropenia or infectious complications. Neither patient was deficient in hepatic glucose-6-phosphatase activities in microsome-disrupted homogenates; both had mutations in the glucose-6-phosphate transporter gene, suggesting an allelic variant of glycogen storage disease type Ib.
Assuntos
Glucose-6-Fosfatase/metabolismo , Glucose-6-Fosfato/genética , Doença de Depósito de Glicogênio Tipo I/enzimologia , Doença de Depósito de Glicogênio Tipo I/genética , Adulto , Criança , Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Humanos , Mutação , NeutropeniaRESUMO
Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in N-acetylgalactosamine-6-sulfate sulfatase (GALNS). In previous studies, we have found two common mutations in Caucasians and Japanese, respectively. To characterize the mutational spectrum in various ethnic groups, mutations in the GALNS gene in Colombian MPS IVA patients were investigated, and genetic backgrounds were extensively analyzed to identify racial origin, based on mitochondrial DNA (mtDNA) lineages. Three novel missense mutations never identified previously in other populations and found in 16 out of 19 Colombian MPS IVA unrelated alleles account for 84.2% of the alleles in this study. The G301C and S162F mutations account for 68.4% and 10.5% of mutations, respectively, whereas the remaining F69V is limited to a single allele. The skewed prevalence of G301C in only Colombian patients and haplotype analysis by restriction fragment length polymorphisms in the GALNS gene suggest that G301C originated from a common ancestor. Investigation of the genetic background by means of mtDNA lineages indicate that all our patients are probably of native American descent.
Assuntos
Condroitina Sulfatases/genética , Mucopolissacaridose IV/enzimologia , Mucopolissacaridose IV/genética , Mutação Puntual , Povo Asiático/genética , Sequência de Bases , Colômbia , Primers do DNA/genética , DNA Mitocondrial/genética , Feminino , Humanos , Indígenas Sul-Americanos/genética , Masculino , Mucopolissacaridose IV/classificação , Fenótipo , Filogenia , Polimorfismo Conformacional de Fita SimplesRESUMO
alpha-Amylase inhibitors from wheat (Triticum aestivum) cultivar Iapar 28-Igapó were extracted with water in a 1:10 (w:v) ratio and precipitated with ammonium sulfate between 20-50% saturation, followed by DEAE and CM-cellulose chromatography. One inhibitor was purified and designated as CMC-IB, and had electrophoretic mobilities of 0.23 and 0.54 in alkaline and acidic conditions, respectively. This inhibitor was 750 times more active on human salivary alpha-amylase (HSSA) than porcine pancreatic o-amylase (PPA). The preincubation time required for maximum complexation with HSA was 20 minutes and optimum pH of inhibition was 7.5. The inhibitor CMC-IB was stable at 0 degrees C and maintained 50% of inhibitory activity against HSA, when incubated at 98 degrees C for one hour.