998 resultados para Delta-7-sterol Reductase


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The active accretional features that have developed along the modern Nile Delta promontories during shoreline retreat are analysed using topographic maps, remote imagery, ground and hydrographic surveys, together providing 15 time-slice maps (1922-2000) at Rosetta and 14 time-slice maps (1909-2000) at Damietta. Small double sandy spits developed and persisted at Rosetta between 1986 and 1991. At Damietta, a much larger single spit, 9 km long, formed approximately east of the mouth of the Damietta Nile branch between 1955 and 1972, although its source has now been depleted. Both the Rosetta and Damietta inlets are associated with submerged mouth bars that accumulated prior to the damming of the Nile, but that continue to contribute to local sedimentation problems, particularly at Rosetta. The development of the active accretional features along the Nile promontories reflects a combination of factors including sediment availability, transport pathways from source areas, a decrease in the magnitude of Nile flood discharges, as well as the impact of protective structures at the river mouths.

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Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in an hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main precursor of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homestasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature.

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A new series of non-stoichiometric sulfides Ga1−xGexV4S8−δ (0≤x≤1; δ≤0.23) has been synthesized at high temperatures by heating stoichiometric mixtures of the elements in sealed quartz tubes. The samples have been characterized by powder X-ray diffraction, SQUID magnetometry and electrical transport-property measurements. Structural analysis reveals that a solid solution is formed throughout this composition range, whilst thermogravimetric data reveal sulfur deficiency of up to 2.9% in the quaternary phases. Magnetic measurements suggest that the ferromagnetic behavior of the end-member phase GaV4S8 is retained at x≤0.7; samples in this composition range showing a marked increase in magnetization at low temperatures. By contrast Ga0.25Ge0.75V4S8−δ appears to undergo antiferromagnetic ordering at ca. 15 K. All materials with x≠1 are n-type semiconductors whose resistivity falls by almost six orders of magnitude with decreasing Ga content, whilst the end-member phase GeV4S8−δ is a p-type semiconductor. The results demonstrate that the physical properties are determined principally by the degree of electron filling of narrow-band states arising from intracluster V–V interactions.

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We have previously demonstrated that PAS-1, a 200 kDa protein from Ascaris suum, has a potent immunomodulatory effect on humoral and cell-mediated responses induced by APAS-3 (an allergenic protein from A. suum) or unrelated antigens. In this study, we investigated the mechanisms by which PAS-1 is able to induce this effect on an allergic airway inflammation induced by OVA in mice. C57BL/6 mice were adoptively transferred on day 0 with seven different PAS-1-primed cell populations: PAS-1-primed CD19(+) or B220(+) or CD3(+) or CD4(+) or CD8(+) or CD4(+) CD25) or CD4(+) CD25(+) lymphocytes. These mice were immunized twice with OVA and alum by intraperitoneal route (days 0 and 7) and challenged twice by intranasal route (days 14 and 21). Two days after the last challenge, the airway inflammation was evaluated by antibody levels, cellular migration, eosinophil peroxidase levels, cytokine and eotaxin production, and pulmonary mechanical parameters. Among the adoptively transferred primed lymphocytes, only CD4(+) CD25(+), CD8(+) or the combination of both T cells impaired the production of total IgE and OVA-specific IgE and IgG1 antibodies, eosinophilic airway inflammation, Th2-type cytokines (IL-4, IL-5 and IL-13), eotaxin release and airway hyperreactivity. Moreover, airway recruited cells from CD4(+) CD25(+) and CD8(+) T-cell recipient secreted more IL-10/TGF-beta and IFN-gamma, respectively. Moreover, we found that PAS-1 expands significantly the number of CD4(+) CD25(+) FoxP3(+) and CD8(+) gamma delta TCR(+) cells. In conclusion, these findings demonstrate that the immunomodulatory effect of PAS-1 is mediated by these T-cell subsets.

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We analyze the potential of the CERN Large Hadron Collider running at 7 TeV to search for deviations from the Standard Model predictions for the triple gauge boson coupling ZW(+)W(-) assuming an integrated luminosity of 1 fb(-1). We show that the study of W(+)W(-) and W(+/-)Z productions, followed by the leptonic decay of the weak gauge bosons can improve the present sensitivity on the anomalous couplings Delta g(1)(Z), Delta kappa(Z), lambda(Z), g(4)(Z), and (lambda) over bar (Z) at the 2 sigma level. (C) 2010 Elsevier B.V. All rights reserved.

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A thermodynamic study involving 7-nitro-1,3,5-triaza adamantane, 1, and its interaction with metal cations in nonaqueous media is first reported. Solubility data of 1 in various solvents were used to derive the standard Gibbs energies of solution, Delta G(s)degrees in these solvents. The effect of solvation in the different media was assessed from the Gibbs energy of transfer taking acetonitrile as a reference solvent. (1)H NMR studies of the interaction of 1 and metal cations were carried out in CD(3)CN and CD(3)OD and the data are reported. Conductance measurements revealed that this ligand forms lead(II) or zinc complexes of 1: 1 stoichiometry in acetonitrile. It also revealed a stoichiometry of two molecules of 1 per mercury(II) and two cadmiu (II) ions per molecule of 1. The addition of silver salt to 1 led to the precipitation of the silver-1 complex which was isolated and characterized by X-ray crystallography. At variance with conductance measurements in solution, in the solid state the X-ray structure show`s a 1:1 stoichiometry in the Hg(II) complex. The themiodynamics of complexation of 1 and these cations provide a quantitative assessment of the selective behavior of this ligand for ions of environmental relevance.

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A few years ago, it was reported that ozone is produced in human atherosclerotic arteries, on the basis of the identification of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3 beta-hydroxy-5 beta-hydroxy-B-norcholestane-6 beta-carboxaldehyde (ChAld) as their 2,4-dinitrophenylhydrazones. The formation of endogenous ozone was attributed to water oxidation catalyzed by antibodies, with the formation of dihydrogen trioxide as a key intermediate. We now report that ChAld is also generated by the reaction of cholesterol with singlet molecular oxygen [O(2) ((1)Delta(g))] that is produced by photodynamic action or by the thermodecomposition of 1,4-dimethylnaphthalene endoperoxide, a defined pure chemical source of O(2) ((1)Delta(g)). On the basis of (18)O-labeled ChAld mass spectrometry, NMR, light emission measurements, and derivatization studies, we propose that the mechanism of ChAld generation involves the formation of the well-known cholesterol 5 alpha-hydroperoxide (5 alpha-OOH) (the major product of O(2) ((1)Delta(g))-oxidation of cholesterol) and/or a 1,2-dioxetane intermediate formed by O(2) ((1)Delta(g)) attack at the Delta(5) position. The Hock cleavage of 5 alpha-OOH (the major pathway) or unstable cholesterol dioxetane decomposition (a minor pathway, traces) gives a 5,6-secosterol intermediate, which undergoes intramolecular aldolization to yield ChAld. These results show clearly and unequivocally that ChAld is generated upon the reaction of cholesterol with O(2) ((1)Delta(g)) and raises questions about the role of ozone in biological processes.

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In mammalian membranes, cholesterol is concentrated in lipid rafts. The generation of cholesterol hydroperoxides (ChOOHs) and their decomposition products induces various types of cell damage. The decomposition of some organic hydroperoxides into peroxyl radicals is known to be a potential source of singlet molecular oxygen [O(2) ((1)Delta(g))] in biological systems. We report herein on evidence of the generation of O(2) ((1)Delta(g)) from ChOOH isomers in solution or in liposomes containing ChOOHs, which involves a cyclic mechanism from a linear tetraoxide intermediate originally proposed by Russell. Characteristic light emission at 1270 nm, corresponding to O(2) ((1)Delta(g)) monomolecular decay, was observed for each ChOOH isomer or in liposomes containing ChOOHs. Moreover, the presence of O(2) ((1)Delta(g)) was unequivocally demonstrated using the direct spectral characterization of near-infrared light emission. Using (18)O-labeled cholesterol hydroperoxide (Ch(18)O(18)OH), we observed the formation of (18)O-labeled O(2) ((1)Delta(g)) [(18)O(2) ((1)Delta(g))] by the chemical trapping of (18)O(2) ((1)Delta(g)) with 9,10-diphenylanthracene (DPA) and detected the corresponding (18)O-labeled DPA endoperoxide (DPA(18)O(18)O) and the (18)O-labeled products of the Russell mechanism using high-performance liquid chromatography coupled to tandem mass spectrometry. Photoemission properties and chemical trapping clearly demonstrate that the decomposition of Ch(18)O(18)OH generates (18)O(2) ((1)Delta(g)), which is consistent with the Russell mechanism and points to the involvement of O(2) ((1)Delta(g)) in cholesterol hydroperoxide-mediated cytotoxicity.

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Oxidation of cholesterol (Ch) by a variety of reactive oxygen species gives rise mainly to hydroperoxides and aldehydes. Despite the growing interest in Ch-oxidized products, the detection and characterization of these products is still a matter of concern. In this work, the main Ch-oxidized products, namely, 3 beta-hydroxycholest-5-ene-7 alpha-hydroperoxide (7 alpha-OOH), 3 beta-5 alpha-cholest-6-ene-5-hydroperoxide (5 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 alpha-hydroperoxide (6 alpha-OOH), 3 beta-hydroxycholest-4-ene-6 beta-hydroperoxide (6 beta-OOH), and 3 beta-hydroxy-5 beta-hydroxy-B-norcholestane-6 beta-carboxaldehyde (ChAld), were detected in the same analysis using high-performance liquid chromatography (HPLC) coupled to dopant assisted atmospheric pressure photoionization tandem mass spectrometry. The use of selected reaction monitoring mode (SRM) allowed a sensitive detection of each oxidized product, while the enhanced product ion mode (EPI) helped to improve the confidence of the analyses. Isotopic labeling experiments enabled one to elucidate mechanistic features during fragmentation processes. The characteristic fragmentation pattern of Ch-oxidized products is the consecutive loss of 1120 molecules, yielding cationic fragments at m/z 401, 383, and 365. Homolytic scissions of the peroxide bond are also seen. With (18)O-labeling approach, it was possible to establish a fragmentation order for each isomer. The SRM transitions ratio along with EPI and (18)O-labeled experiments give detailed information about differences for water elimination, allowing a proper discrimination between the isomers:Phis is of special interest considering the emerging role of Ch-oxidized products in the development of diseases.

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A new approach for the synthesis of alpha,beta-unsaturated delta-lactones, a unit present in many natural products with interesting biological activities is described. The approach was based on the use of a vinyl telluride, and it is complementary to the methods using ring-closing metathesis. The sequence was performed in good overall yield with retention of the Z-double bond geometry. (C) 2011 Elsevier Ltd. All rights reserved.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Os autores padronizaram métodos para a avaliação da atividade da glicose-6-fosfato desidrogenase e glutationa redutase. O princípio geral do primeiro método baseou-se na formação de metahemoglobina pelo nitrito de sódio, seguido da estimulação da via das pentoses pelo azul de metileno. Foram estudados 46 indivíduos adultos, sendo 23 do sexo masculino e 23 do feminino, não deficientes em glicose-6-fosfato desidrogenase (G6PD), com idades variando entre 20 e 30 anos. Os resultados revelaram que a redução da metahemoglobina pelo azul de metileno para sangue total, foram de 154.50 e 139.90 mg/min (p<0.05) respectivamente para o sexo masculino e feminino. Para hemácias lavadas os valores foram de 221.10 e 207.85 mg/min (n.s.) respectivamente. Estas observações permitiram concluir que ao se empregar hemácias lavadas e 0.7 g% de concentração de nitrito de sódio, por um lado não houve diferença entre os sexos e por outro, abreviou o tempo de leitura da quantidade residual de metahemoglobina para 90 minutos. A avaliação da atividade da glutationa redutase foi feita baseado no fato de que a cistamina (agente tiol) liga-se aos grupos SH da hemoglobina formando complexos. Estes complexos são revertidos pela ação da glutationa redutase, ocorrendo conjuntamente nesta reação a redução da metahemoglobina. Foram estudados 32 indivíduos adultos, sendo 16 do sexo masculino e 16 do feminino, não deficientes em G6PD, com idades variando entre 20 e 30 anos. Os resultados revelaram valores de redução da metahemoglobina pela cistamina de 81.27 e 91.13 mg/min (p<0.01) respectivamente para o sexo masculino e feminino. Estas observações permitiram concluir que o emprego de hemácias lavadas e 0.1 molar de concentração de cistamina torna possível a leitura da quantidade residual de metahemoglobina aos 180 minutos de incubação. A atividade da glutationa redutase avaliada por meio da redução da metahemoglobina pela cistamina, foi estudada em 14 indivíduos do sexo feminino antes e após o tratamento com 10 mg por dia de riboflavina durante 8 dias. Os resultados foram de 73.69 e 94.26 mg/min (p<0.01) antes e após o tratamento. Estas observações permitiram concluir que a oferta de riboflavina, mesmo para indivíduos normais, aumenta a atividade da glutationa redutase. Foram ainda avaliados 3 indivíduos da raça negra e deficientes em G6PD, sendo 2 do sexo masculino e 1 do feminino. Houve ativação parcial da G6PD e glutationa redutase, sendo estas alterações mais intensas nos indivíduos do sexo masculino. Considerando-se a raça e as características laboratoriais observadas, foi possível sugerir que a deficiência em G6PD verificada é do tipo Africano, bem como, permitiu considerar os indivíduos do sexo feminino coin o sendo heterozigoto para esta deficiência. Por fim, a análise dos resultados em seu conjunto permitiu concluir que os métodos propostos se mostraram eficientes para avaliar a atividade da G6PD e glutationa redutase. Esta última é dependente da via das pentoses, geradora de NADPH e da riboflavina, vitamina precursora de FAD.

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This study proposed the use of the stable isotope technique to track the type of food utilized by pacu Piaractus mesopotamicus larvae during their development, and to identify the moment when the larvae start using nutrients from the dry diet by retaining its carbon and nitrogen atoms in their body tissues. Five-day-old pacu larvae at the onset of exogenous feeding were fed Artemia nauplii or formulated diet exclusively; nauplii+formulated diet during the entire period; or were weaned from nauplii to a dry diet after 3, 6 or 12 days after the first feeding. delta(13)C and delta(15)N values for Artemia nauplii were -15.1 parts per thousand and 4.7 parts per thousand, respectively, and -25.0 parts per thousand and 7.4 parts per thousand for the dry diet. The initial isotopic composition of the larval tissue was -20.2 parts per thousand and 9.5 parts per thousand for delta(13)C and delta(15)N respectively. Later, at the end of a 42-day feeding period, larvae fed Artemia nauplii alone reached values of -12.7 parts per thousand and 7.0 parts per thousand for delta(13)C and delta(15)N respectively. Larvae that received the formulated diet alone showed values of -22.7 parts per thousand for delta(13)C and 9.6 parts per thousand for delta(15)N. The stable isotope technique was precise, and the time at which the larvae utilized Artemia nauplii, and later dry diet as a food source could be clearly defined.