RESUMO
Gene therapy has been adapted, from the laboratory to the clinic, to treat retinopathies. In contrast to subretinal route, intravitreal delivery of AAV vectors displays the advantage of bypassing surgical injuries, but the viral particles are more prone to be nullified by the host neutralizing factors. To minimize such suppression of therapeutic effect, especially in terms of AAV2 and its derivatives, we introduced three serine-to-glycine mutations, based on the phosphorylation sites identified by mass spectrum analysis, to the XL32 capsid to generate a novel serotype named AAVYC5. Via intravitreal administration, AAVYC5 was transduced more effectively into multiple retinal layers compared with AAV2 and XL32. AAVYC5 also enabled successful delivery of anti-angiogenic molecules to rescue laser-induced choroidal neovascularization and astrogliosis in mice and non-human primates. Furthermore, we detected fewer neutralizing antibodies and binding IgG in human sera against AAVYC5 than those specific for AAV2 and XL32. Our results thus implicate this capsid-optimized AAVYC5 as a promising vector suitable for a wide population, particularly those with undesirable AAV2 seroreactivity.
Assuntos
Capsídeo , Neovascularização de Coroide , Humanos , Camundongos , Animais , Capsídeo/metabolismo , Dependovirus/genética , Sorogrupo , Transdução Genética , Neovascularização de Coroide/terapia , Tropismo , Proteínas do Capsídeo/metabolismo , Vetores Genéticos/genéticaRESUMO
In the title compound, C(18)H(16)N(2)O(2), the central pyridazine ring forms dihedral angles of 77.08â (5)° and 84.62â (5)° with the two benzene rings. The dihedral angle between the two benzene rings is 68.18â (4)°. A very weak intra-molecular C-Hâ¯N hydrogen bond and an intra-molecular C-Hâ¯π inter-action occur. The crystal structure is stabilized by weak inter-molecular C-Hâ¯O hydrogen bonds and weak C-Hâ¯π and π-π stacking inter-actions [centroid-centroid distance = 3.6867â (10)â Å].
RESUMO
To investigate the impacts of large hydropower station in Gufu River on benthic algae, monthly samplings were conducted from September 2004 to June 2007 at the site GF04 which was impacted by the hydropower station, with the site GL03 in Gaolan River as reference. During sampling period, no significant differences were observed in the main physicochemical variables between GF04 and GL03, but the hydrodynamics differed significantly. GL03 was basically at a status of slow flow; while GF04, owing to the discharging from the reservoir, was at a riffle status during more than 60% of the sampling period. Such a difference in hydrodynamics induced significant differences in the community similarity of benthic algae and the relative abundance of unattached diatoms, erect diatoms, and stalked diatoms between GF04 and GL03, which could better reflect the impacts of irregular draw-off by large hydropower station on river eco-system.
Assuntos
Ecossistema , Monitoramento Ambiental/métodos , Eucariotos/crescimento & desenvolvimento , Água Doce/análise , Centrais Elétricas , China , Eucariotos/classificação , Dinâmica Populacional , RiosRESUMO
To study the seasonal dynamics of macrozoobenthos community in Xiangxi River, the individuals of macrozoobenthos in the River were quantitatively monitored. A total of 197 taxa belonging to 6 class and 68 families were collected, among which, Baetis spp., Epeorus spp., and Nemoura spp. were the dominant groups, and their compositions varied with seasons. The macrozoobenthos community was most complicated in winter, followed by in spring and autumn, and the simplest in summer. Gather-collector was the main component of functional feeding groups in Xiangxi River system, followed by scraper, predator, and filter-collector, while shredder only accounted for a small part. Canonical correspondence analysis showed that the factors affecting the macrozoobenthos community were dissimilar among seasons. In summer and autumn, nutrients had greater effects; and in all seasons, water depth had definite effects.
Assuntos
Invertebrados/crescimento & desenvolvimento , Invertebrados/fisiologia , Animais , China , Água Doce/análise , Invertebrados/classificação , Dinâmica Populacional , Rios , Estações do AnoRESUMO
An investigation was made from July 2005 to June 2006 to understand the spatial distribution of macroinvertebrates in Xiangxi River, the largest tributary in Hubei portion of Three Gorges Reservoir. The results showed that Ephemeroptera baetis spp., Ephemeroptera epeorus spp., and Plecoptera nemoura spp. were the dominant taxa. There existed greater differences in the habitat characters and in the community structure of macroinvertebrates among the major tributaries of Xiangxi River, and the relative abundance of functional feeding groups could reflect the characters of different habitats. A comparison of the diversity of dominant taxa and their tolerance towards pollution among the major tributaries showed that Jiuchong River had the best habitat, followed by the main stream of Xiangxi River, and Gaolan River and Gufu River. Canonical correspondence analysis showed that the NH4+ -N concentration in the main stream of Xiangxi River, the pH, turbidity, water depth, SiO2, conductance, and alkalinity in Jiuchong River, the turbidity in Gaolan River, and the NH4+ -N and NO3- -N concentrations in Gufu River had significant impact on the community structure of macroinvertebrates.
Assuntos
Biodiversidade , Monitoramento Ambiental , Insetos/crescimento & desenvolvimento , Invertebrados/crescimento & desenvolvimento , Água/análise , Animais , China , Insetos/classificação , Invertebrados/classificação , Nitrogênio/análise , Dinâmica Populacional , Compostos de Amônio Quaternário/análise , Rios , Dióxido de Silício/análiseRESUMO
With the five small hydropowers (SHPs) from up- to downstream of Xiangxi River as test objects, this paper studied the influence of SHPs cascaded exploitation on the phytoplankton in the river. The results showed that phytoplankton assemblages were dominated by diatoms, occupying 95.54% of the total number of species. Achnanthes linearis, A. lanceolata var. elliptica and Cocconeis placentula were the most abundant species, with the relative abundance being 23.96%, 18.62% and 12.48%, respectively. The average algal density at 25 sampling sites was 6.29 x 10(5) ind x L(-1), with the maximum of 1.81 x 10(6) ind x L(-1) and the minimum of 2.35 x 10(5) ind x L(-1). Two-way ANOVA indicated that water flow velocity was the main factor affecting the phytoplankton. The establishment of the cascaded SHPs on the river made the habitat of lower reach has a significant difference with the others, resulting in a dramatic change of many parameters including Margalef diversity index, species richness, generic richness, taxonomic composition, and the percentage of diatoms.