RESUMO
Searches for the lepton number violating K^{+}âπ^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}âπ^{+}µ^{-}e^{+} and π^{0}âµ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}âπ^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}âπ^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}âµ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.
RESUMO
Lipoxygenases (LOXs) are lipid-peroxidizing enzymes that are involved in the metabolism of polyunsaturated fatty acids. Their biological activity includes a membrane binding process whose molecular details are not completely understood. The mechanism of enzyme-membrane interactions is thought to involve conformational changes at the level of the protein tertiary structure, and the extent of such alterations depends on the degree of structural flexibility of the different LOX isoforms. In this study, we have tested the resilience properties of a plant and a mammalian LOX, by using high pressure fluorescence measurements at different temperatures. The binding of LOXs to the lipid bilayer has been characterized using both large and giant unilamellar vesicles and electron transfer particles (inner mitochondrial membranes) as model membranes. The data indicate that the degree of LOXs' flexibility is strictly dependent on the two distinct N- and C-terminal domains that characterize the 3D structure of these enzymes. Furthermore, they demonstrate that increasing the rigidity of protein scaffolding by the presence of an active site ligand impairs the membrane binding ability of LOXs. These findings provide evidence that the amphitropic nature of LOXs is finely tuned by the interaction of the substrate with the residues of the active site, suggesting new strategies for the design of enzyme inhibitors.
Assuntos
Ácido 5,8,11,14-Eicosatetrainoico/química , Bicamadas Lipídicas/química , Inibidores de Lipoxigenase/química , Lipoxigenase/química , Membranas Mitocondriais/química , Domínio Catalítico , Humanos , Membranas Mitocondriais/enzimologiaRESUMO
Two hundred and seventy-one male patients suffering from uncomplicated gonococcal urethritis were treated in an open randomized study with either 250 mg (121 patients) or 500 mg (150 patients) single oral doses of ciprofloxacin. The efficacy of treatment was verified on the third day by direct examination of urethral swabs in 91 patients and by culture and direct microscopic examination in 180 subjects. Cure rates were 100% in the 500 mg group and 96.6% in the 250 mg treated patients. No side effects were seen. Ciprofloxacin appears to be a very effective and safe drug in the treatment of uncomplicated gonococcal urethritis in men.