Perfil característico das atividades 17-hidroxilase e 17,20-liase reveladas por meio do metaboloma de esteroides urinários de pacientes com deficiência de CYP17

OBJECTIVES: (1) Characterize serum (S) and urinary (U) steroid metabolites in complete CYP17 deficiency (cCYP17D); (2) analyze the relative 17α-hydroxylase (17OH) and 17,20-lyase (17,20L) activities in vivo; and (3) comparedata from the two most prevalent mutations in Brazil. SUBJECTS AND METHODS: 20 genotyped cCYP17D patients from a previously reported cohort were homozygous for W406R or R362C; 11 controls were CYP17 wild types (WT). WT and cCYP17D patients had S and U samples drawn to measure: cortisol (F), corticosterone (B), deoxycorticosterone (DOC), 18OH-B, 18OH-DOC, and 17OHP; and tetrahydro (TH)-B, THA, THDOC, THF+5α-THF, TH-cortisone, androsterone, etiocholanolone, 5-pregnenediol, 17OH-pregnenolone and pregnanetriol. RESULTS: Compared to WT, cCYP17D patients had marked elevations of B, DOC, 18OH-B and 18OH-DOC, whereas 17OHP, F and adrenal androgens (AA) were reduced; U steroids parallel S findings. Metabolite ratios revealed that both 17OH and 17,20L activities were impaired in cCYP17D. There were nodifferences between W406R andR362C mutations. CONCLUSIONS: cCYP17D patients show parallel overproduction/overexcretion of 17-deoxysteroids, and marked reduction of F and AA. In addition to 17OH, 17,20-L activity was also impaired in cCYP17D. W406 and R362C mutations disclose similar Sand U patterns.OBJETIVOS: (1) Caracterizar os esteroides séricos (S) e urinários (U) na deficiência completa da CYP17 (DcCYP17); (2) analisar as atividades da 17α-hidroxilase (17OH) e 17,20-liase (17, 20 L) in vivo; e (3) comparar as duas mutações mais prevalentes no Brasil. SUJEITOS E MÉTODOS: 20 pacientes genotipados para a DcCYP17, de uma coorte anterior, eram homozigotos para W406R ou R362C (8 cada); 11 controles eram CYP17 wild types (WT). Amostras de S e U foram colhidas dos WT e pacientes para dosagem de: cortisol (F), corticosterona (B), deoxicorticosterona (DOC), 18-OH-B, 18OH-DOC e 17OHP; e tetraidro(TH)-B, THA, TH-DOC, THF+5α-THF, THE, androsterona, etiocolanolona, 5-pregnenediol, 17OH-pregnenolona e pregnanetriol. RESULTADOS: Comparados aos WT, os pacientes com DcCYP17 revelaram elevações acentuadas de B, DOC, 18OHB e 18OHDOC, enquanto 17OHP, F e andrógenos adrenais (AA) estavam reduzidos. Os esteroides na U acompanham os achados no S. As relações de metabólitos mostraram que as atividades de 17OH e 17,20L estavam reduzidas em pacientes com DcCYP17. Não houve diferenças entre pacientes com as mutações W406R e R362C. CONCLUSÕES: Na DcCYP17, a produção e a excreção dos 17-deoxiesteroides estão aumentadas em paralelo, em contraste com a reduzida produção/excreção de F e AA. As atividades da 17OH e 17,20-L estão diminuídas na DcCYP17. As mutações W406 e R362C apresentam achados semelhantes em S e U.Universidade Federal de São Paulo (UNIFESP) Department of Medicine Division of Endocrinology and MetabolismUniversity of Texas Southwestern Medical Center Department of Clinical SciencesUniversity of Birmingham Division of Medical SciencesUNIFESP, Department of Medicine Division of Endocrinology and MetabolismSciEL

Perfil de ácidos graxos de carne de búfalos terminados em sistemas tradicional e silvipastoril.

The aim of this study was to evaluate the fatty acid profile of the meat of buffalo finished in creating Traditional Systems (ST) and Silvopastoral (SSP) with supplemental feeding. The experiments were performed in the Research Units Animal "Senator Álvaro Adolpho", silvopastoral system and "Dr. Philibert Camargo, "traditional system of creation, belonging to Embrapa Amazônia Oriental, Belém-Pará, Brazil. After the fattening period, eight months, the animals were slaughtered at a commercial abattoir and their carcasses identified, refrigerated for 24 hours. The Longissimus dorsi (kebabs) retained the right half carcass between the 12th and 10th ribs, was ground and stored for determination of acids in lipids extracted from samples and cold reading esters performed by gas chromatography. The experimental design was completely randomized, the data were evaluated by ANOVA and means were compared by 't' test at 5% significance level. The analysis of fatty acid profile reveals a statistical difference (P <0.05), only the percentage of myristic acid (C14: 0) and polyunsaturated fatty acids. In conclusion, therefore, that breeding systems and supplementation are not sufficient to indicate the use of either system, since it must be taken into account also the environmental, social and economic

Elaboração e avaliação sensorial de iogurte de leite de búfala sabor jacaiacá (Poupartia amazonica).

Objetivou-se elaborar e avaliar iogurte de leite de búfala saborizado com jacaiacá (Poupartia amazonica). O leite de búfala (Bubalus bubalis), obtido na Unidade de Pesquisa Animal "Dr. Felisberto Camargo" (01º26'S e 48º24'W), Embrapa Amazônia Oriental, Belém, Pará, foi submetido a tratamento térmico (95 C/5 minutos), resfriado a 45 C e inoculado com 2% de cultura láctica, e resfriado. Depois foi adicionada calda com 35% de polpa da fruta, 35% de sacarose e 30% de água, homogeneizados por cinco minutos. No dia seguinte foi feita avaliação sensorial, com 52 provadores não treinados, no Laboratório de Alimentos da Universidade do Estado do Pará, onde se constatou boa aceitabilidade, com média de 7,1, bem como intenção de compra, onde 55,8%, com certeza comprariam o produto, 42,28% talvez comprassem e 1,92% não comprariam. Esse derivado constitui excelente alternativa para Programas Especiais financiados pelo Governo, com vista à complementar a dieta de estudantes da rede pública, bem como de comunidades de baixa renda, pois é alimento de elevado valor calórico-protéico e baixo custo, além de utilizar matérias-primas produzidas em nível local e gerar renda e trabalho, através do incentivo à produção leiteira e à fruticultura, principalmente na agricultura familiar

Composição centesimal, física e sensorial de carne de búfalos terminados em sistema tradicional e silvipastoril na Amazônia Oriental.

The aim of this study was to evaluate the physical and sensory characteristics of buffalo meat ended Traditional Systems and Silvopastoral. The experiments were performed in the Research Units Animal "Senator Álvaro Adolpho", SSP installed and "Dr. Philibert Camargo "(ST), belonging to Embrapa Amazônia Oriental, Belém-Pará. After this period the animals were slaughtered at a commercial packing plant and their carcasses were identified and cooled for 24 hours. The right side carcass was cut between the 12th and 13th ribs and removed the Longissimus dorsi (kebabs), for analysis of pH, texture and color lenses, weight loss by cooking, ability to retain water, determining the composition proximate and sensory evaluation. The experimental design was completely randomized, the data submitted to analysis of variance and means were compared by 't' test at 5%. There were no differences (p> 0.05) in chemical composition and physical analysis between meat derived from animals of the two systems. Among the evaluated sensory only the "aroma" differed statistically. It is still early to suggest the use of either system, just based on the quality of meat produced, should be considered also the environmental, social and economic

Extração do óleo de babaçu (Orbignya Speciosa) provenientes da Embrapa Meio-­Norte visando a produção de biodiesel.

O óleo de babaçu é constituído por ácidos graxos saturados e insaturados sendo que o ácido láurico (C 12:0) é predominante. A quantidade de ácidos graxos insaturados na composição do biodiesel esta relacionada à matéria-prima utilizada, que viabiliza a aceleração da reação de oxidação pela exposição ao oxigênio em altas temperaturas, prejudicando motores. O alto índice de acidez também afeta a estabilidade do biodiesel, provocando reações indesejáveis que promovem a formação de produtos que aceleram o envelhecimento do produto. Dentre esses motivos a analise do óleo de babaçu torna se bastante eficiente, pois o babaçu é uma fonte de óleo economicamente viável, e bastante promissora já que se refere a um produto abundante na nossa região

Enterobactin-Mediated Delivery of β-Lactam Antibiotics Enhances Antibacterial Activity against Pathogenic Escherichia coli

The design, synthesis, and characterization of enterobactin–antibiotic conjugates, hereafter Ent-Amp/Amx, where the β-lactam antibiotics ampicillin (Amp) and amoxicillin (Amx) are linked to a monofunctionalized enterobactin scaffold via a stable poly(ethylene glycol) linker are reported. Under conditions of iron limitation, these siderophore-modified antibiotics provide enhanced antibacterial activity against Escherichia coli strains, including uropathogenic E. coli CFT073 and UTI89, enterohemorrhagic E. coli O157:H7, and enterotoxigenic E. coli O78:H11, compared to the parent β-lactams. Studies with E. coli K-12 derivatives defective in ferric enterobactin transport reveal that the enhanced antibacterial activity observed for this strain requires the outer membrane ferric enterobactin transporter FepA. A remarkable 1000-fold decrease in minimum inhibitory concentration (MIC) value is observed for uropathogenic E. coli CFT073 relative to Amp/Amx, and time-kill kinetic studies demonstrate that Ent-Amp/Amx kill this strain more rapidly at 10-fold lower concentrations than the parent antibiotics. Moreover, Ent-Amp and Ent-Amx selectively kill E. coli CFT073 co-cultured with other bacterial species such as Staphylococcus aureus, and Ent-Amp exhibits low cytotoxicity against human T84 intestinal cells in both the apo and iron-bound forms. These studies demonstrate that the native enterobactin platform provides a means to effectively deliver antibacterial cargo across the outer membrane permeability barrier of Gram-negative pathogens utilizing enterobactin for iron acquisition.Pacific Southwest Regional Center of Excellence for Biodefense and Emerging Infectious DiseaseKinship Foundation. Searle Scholars ProgramMassachusetts Institute of Technology. Department of Chemistr

Identification of Functional Differences in Metabolic Networks Using Comparative Genomics and Constraint-Based Models

Genome-scale network reconstructions are useful tools for understanding cellular metabolism, and comparisons of such reconstructions can provide insight into metabolic differences between organisms. Recent efforts toward comparing genome-scale models have focused primarily on aligning metabolic networks at the reaction level and then looking at differences and similarities in reaction and gene content. However, these reaction comparison approaches are time-consuming and do not identify the effect network differences have on the functional states of the network. We have developed a bilevel mixed-integer programming approach, CONGA, to identify functional differences between metabolic networks by comparing network reconstructions aligned at the gene level. We first identify orthologous genes across two reconstructions and then use CONGA to identify conditions under which differences in gene content give rise to differences in metabolic capabilities. By seeking genes whose deletion in one or both models disproportionately changes flux through a selected reaction (e.g., growth or by-product secretion) in one model over another, we are able to identify structural metabolic network differences enabling unique metabolic capabilities. Using CONGA, we explore functional differences between two metabolic reconstructions of Escherichia coli and identify a set of reactions responsible for chemical production differences between the two models. We also use this approach to aid in the development of a genome-scale model of Synechococcus sp. PCC 7002. Finally, we propose potential antimicrobial targets in Mycobacterium tuberculosis and Staphylococcus aureus based on differences in their metabolic capabilities. Through these examples, we demonstrate that a gene-centric approach to comparing metabolic networks allows for a rapid comparison of metabolic models at a functional level. Using CONGA, we can identify differences in reaction and gene content which give rise to different functional predictions. Because CONGA provides a general framework, it can be applied to find functional differences across models and biological systems beyond those presented here

Global patterns and drivers of ecosystem functioning in rivers and riparian zones

River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.peerReviewe