64 resultados para endosome escape


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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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At present, gene transfection insufficient efficiency is a major drawback of non-viral gene therapy. The 2 main types of delivery systems deployed in gene therapy are based on viral or non-viral gene carriers. Several non-viral modalities can transfer foreign genetic material into the human body. To do so, polycation-based gene delivery methods must achieve sufficient efficiency in the transportation of therapeutic genes across various extracellular and intracellular barriers. These barriers include interactions with blood components, vascular endothelial cells and uptake by the reticuloendothelial system. Furthermore, the degradation of therapeutic DNA by serum nucleases is a potential obstacle for functional delivery to target cells. Cationic polymers constitute one of the most promising approaches to the use of viral vectors for gene therapy. A better understanding of the mechanisms by which DNA can escape from endosomes and traffic to enter the nucleus has triggered new strategies of synthesis and has revitalized research into new polycation-based systems. The objective of this review is to address the state of the art in gene therapy with synthetic and natural polycations and the latest advances to improve gene transfer efficiency in cells.

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We consider an electric charge, minimally coupled to the Maxwell field, rotating around a Schwarzschild black hole. We investigate how much of the radiation emitted from the swirling charge is absorbed by the black hole and show that most of the photons escape to infinity. For this purpose we use the Gupta-Bleuler quantization of the electromagnetic field in the modified Feynman gauge developed in the context of quantum field theory in Schwarzschild spacetime. We obtain that the two photon polarizations contribute quite differently to the emitted power. In addition, we discuss the accurateness of the results obtained in a full general relativistic approach in comparison with the ones obtained when the electric charge is assumed to be orbiting a massive object due to a Newtonian force.

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We discuss modified gravity which includes negative and positive powers of curvature and provides gravitational dark energy. It is shown that in GR plus a term containing a negative power of curvature, cosmic speed-up may be achieved while the effective phantom phase (with w less than -1) follows when such a term contains a fractional positive power of curvature. Minimal coupling with matter makes the situation more interesting: even 1/R theory coupled with the usual ideal fluid may describe the (effective phantom) dark energy. The account of the R(2) term (consistent modified gravity) may help to escape cosmic doomsday.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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A probable capture of Phobos into an interesting resonance was presented in our previous work. With a simple model, considering Mars in a Keplerian and circular orbit, it was shown that once captured in the resonance, the inclination of the satellite reaches very high values. Here, the integrations are extended to much longer times and escape situations are analyzed. These escapes are due to the interaction of new additional resonances, which appear as the inclination starts to increase reaching some specific values. Compared to classical capture in mean motion resonances, we see some interesting differences in this problem. We also include the effect of Mars' eccentricity in the process of the capture. The role played by this eccentricity becomes important, particularly when Phobos encounters a double resonance at a approximate to 2.619R(M). Planetary perturbations acting on Mars and variation of its equator are also included. In general, some possible scenarios of the future of Phobos are presented.

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Gravitational capture can be used to explain the existence of the irregular satellites of giants planets. However, it is only the first step since the gravitational capture is temporary. Therefore, some kind of non-conservative effect is necessary to to turn the temporary capture into a permanent one. In the present work we study the effects of Jupiter mass growth for the permanent capture of retrograde satellites. An analysis of the zero velocity curves at the Lagrangian point L-1 indicates that mass accretion provides an increase of the confinement region ( delimited by the zero velocity curve, where particles cannot escape from the planet) favoring permanent captures. Adopting the restricted three-body problem, Sun-Jupiter-Particle, we performed numerical simulations backward in time considering the decrease of M-4. We considered initial conditions of the particles to be retrograde, at pericenter, in the region 100 R-4 less than or equal to a less than or equal to 400 R-4 and 0 less than or equal to e < 0.5. The results give Jupiter's mass at the moment when the particle escapes from the planet. Such values are an indication of the necessary conditions that could provide capture. An analysis of these results shows that retrograde satellites would be captured as soon as they get inside the Hills' radius and after that they keep migrating toward the planet while it is growing. For the region where the orbits of the four old retrograde satellites of Jupiter ( Ananke, Carme, Pasiphae and Sinope) are located we found that such satellites could have been permanently captured when Jupiter had between 62% and 93% of its present mass.

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

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Some dynamical properties of an ensemble of trajectories of individual (non-interacting) classical particles of mass m and charge q interacting with a time-dependent electric field and suffering the action of a constant magnetic field are studied. Depending on both the amplitude of oscillation of the electric field and the intensity of the magnetic field, the phase space of the model can either exhibit: (i) regular behavior or (ii) a mixed structure, with periodic islands of regular motion, chaotic seas characterized by positive Lyapunov exponents, and invariant Kolmogorov-Arnold-Moser curves preventing the particle to reach unbounded energy. We define an escape window in the chaotic sea and study the transport properties for chaotic orbits along the phase space by the use of scaling formalism. Our results show that the escape distribution and the survival probability obey homogeneous functions characterized by critical exponents and present universal behavior under appropriate scaling transformations. We show the survival probability decays exponentially for small iterations changing to a slower power law decay for large time, therefore, characterizing clearly the effects of stickiness of the islands and invariant tori. For the range of parameters used, our results show that the crossover from fast to slow decay obeys a power law and the behavior of survival orbits is scaling invariant. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4772997]

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LASSBio-767 [(-)-3-O-acetyl-spectaline] and LASSBio-822 [(-)-3-O-tert-Boc-spectaline] were recently described as cholinesterase inhibitors derived from the natural piperidine alkaloid (-)-spectaline, obtained from the flowers of Senna spectabilis (Fabaccae). We investigated their mechanism of inhibition of acetylcholinesterase and their efficacy in reversing scopolamine-induced amnesia. Competition assays with the substrate acetylthiocholine showed a concentration-dependent reduction in rat brain cholinesterase V-max without changes in apparent K-m. The kinetic data for LASSBio-767 and LASSBio-822 were best fit by a model of simple linear noncompetitive inhibition with K-i of 6.1 mu M and 7.5 mu M, respectively. A dilution assay showed a fast and complete reversal of inhibition, independent of incubation time. Simulated docking of the compounds into the catalytic gorge of Torpedo acetylcholinesterase showed interactions with the peripheral anionic site, but not with the catalytic triad. Anti-amnestic effects in mice were assessed in a step-down passive avoidance test and in the Morris water maze 30 min after injection of scopolamine (1 mg/kg i.p.). Saline, LASSBio-767, or LASSBio-822 was administered 15 min before scopolamine. Both compounds reversed the scopolamine-induced reduction in step-down latency at 0.1 mg/kg i.p. LASSBio-767 reversed scopolamine-induced changes in water maze escape latency at 1 mg/kg i.p. or p.o., while its cholinergic side effects were absent or mild up to 30 mg/kg i.p. (LD50 above 100 mg/kg i.p.). Thus, the (-)-spectaline derivatives are potent cholinergic agents in vivo, with a unique profile combining noncompetitive cholinesterase inhibition and CNS selectivity, with few peripheral side effects. (C) 2007 Elsevier B.V. All rights reserved.

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É apresentada uma síntese sobre os peixes do Alto Paraná, com base em dados de coleções, dados de literatura e novas coletas. Trezentas e dez espécies, de 11 ordens e 38 famílias, são referidas para a drenagem, aumentando significativamente números anteriores. Dentre as espécies da área, 236 (76,1%) são autóctones, 67 (21,6%) alóctones e sete (2,3%) exóticas. As principais causas de ocorrência de espécies não nativas (alóctones e exóticas) foram a dispersão a partir do baixo Paraná, após a construção do Reservatório de Itaipu e o escape de pisciculturas. A maior parte das espécies referidas (65%) tem porte pequeno, sendo menor que 21 cm de comprimento; dentre essas, a maioria ocorre apenas em riachos e cabeceiras. Apesar da ictiofauna do Alto Paraná ser uma das melhor conhecidas e mais estudadas, o número de espécies descritas ou referidas para a área tem crescido exponencialmente, o que indica que a riqueza apresentada está longe de representar a realidade. de fato, várias novas espécies têm sido descritas nos últimos anos e cerca de 50 novas espécies, já reconhecidas, estão em fase de descrição. A melhoria no conhecimento sobre a ictiofauna do Alto Paraná é proporcional ao número de pesquisadores envolvidos em estudos na bacia e reflete, de modo inequívoco, iniciativas recentes que têm estimulado e incrementado pesquisas taxonômicas, facilitado o acesso ao material depositado em coleções científicas e aumentado as coletas em áreas e ambientes pouco amostrados. Entretanto, mantido o ritmo de descrições de novas espécies ocorrido até agora nessa última década, as 50 novas espécies já reconhecidas estariam descritas apenas dentro de dez anos, um tempo demasiadamente longo. Por essa razão é muito importante que a comunidade científica e os órgãos de fomento encontrem e viabilizem iniciativas de modo a aumentar esse ritmo de descrições de novos táxons e disponibilizar esses novos nomes mais rapidamente.

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Estudaram-se os procedimentos de indexação biológica e bioquímica em um experimento de avaliação do uso de viróides como agentes ananicantes para pomeleiro 'Marsh Seedless'. em algumas parcelas, houve segregação de viróides, sendo que, em duas, a segregação foi de CEVd (viróide da exocorte dos citros) e, em outras duas, não foi detectada a presença de CVd-II (viróide dos citros II). Como conseqüência desta segregação, não ocorreram sintomas típicos da exocorte em cidra nas parcelas nas quais houve segregação de CEVd, o que ocorreu nas parcelas em que a segregação foi de CVd-II, indicando que é necessária a presença de CEV para a manifestação de sintomas típicos de exocorte em cidra. Numa quinta parcela, não se detectaram viróides, provavelmente, devido à ausência dos mesmos no material de inoculação do teste biológico (escape), já que a planta de campo teve desenvolvimento vegetativo normal e ausência de sintomas no tronco. Finalmente, em uma sexta parcela, o que ocorreu, foi uma segregação drástica, não relatada na literatura, já que a planta de campo mostrou redução de porte e sintomas no tronco. A coleta de varetas para indexação deve ser mais rigorosa em função da ocorrência de segregação.

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As videiras da região de Jales, Estado de São Paulo, têm sido intensamente atacadas pelo ácaro-rajado, Tetranychus urticae Koch. O presente trabalho teve por objetivo comparar cultivares de uva quanto à adequação como hospedeiras da espécie. em experimento de campo, naquele local, a ocorrência da praga, ao longo de 12 meses, foi acompanhada nas cultivares de uvas finas, Itália e Benitaka, e na cultivar de uva rústica, Niagara Rosada. No laboratório, a biologia de T. urticae foi estudada nessas três cultivares e na 'Redimeire'. Na cultivar Niagara Rosada, o ácaro-rajado apresentou menor fecundidade e menor sobrevivência, indicando a presença de mecanismos de resistência por antibiose. Além disso, houve maior tentativa de fuga dessa cultivar, sugerindo resistência por não preferência.

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