Eye drop delivery of nano-polymeric micelle formulated genes with cornea-specific promoters

BACKGROUND: This study evaluates the eye drop delivery of genes with cornea-specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms. METHODS: Three PM-formulated plasmids (pCMV-Lac Z, pK12-Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta-Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine-aspartic acid) peptide. RESULTS: The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment. CONCLUSIONS: Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport.     

Mechanisms of the acute ischemia-induced arrhythmogenesis--a simulation study

The underlying ionic mechanisms of ischemic-induced arrhythmia were studied by the computer simulation method. To approximate the real situation, ischemic cells were simulated by considering the three major component conditions of acute ischemia (elevated extracellular K(+) concentration, acidosis and anoxia) at the level of ionic currents and ionic concentrations, and a round ischemic zone was introduced into a homogeneous healthy sheet to avoid sharp angle of the ischemic tissue. The constructed models were solved using the operator splitting and adaptive time step methods, and the perturbation finite difference (PFD) scheme was first used to integrate the partial differential equations (PDEs) in the model. The numerical experiments showed that the action potential durations (APDs) of ischemic cells did not exhibited rate adaptation characteristic, resulting in flattening of the APD restitution curve. With reduction of sodium channel availability and long recovery of excitability, refractory period of the ischemic tissue was significantly prolonged, and could no longer be considered as same as APD. Slope of the conduction velocity (CV) restitution curve increased both in normal and ischemic region when pacing cycle length (PCL) was short, and refractory period dispersion increased with shortening of PCL as well. Therefore, dynamic changes of CV and dispersion of refractory period rather than APD were suggested to be the fundamental mechanisms of arrhythmia in regional ischemic myocardium.     

林农复合经营生态体系的研究

林农复合经营以生态经济学的原理,运用现代生物和生态工程方法技术,组成林、农、牧、副、渔有机结合的复合生产体系。它突破了传统林业的单一生产方式,形成以林为主的一个复合的、开放的、具有整体效应的生态系统。这种复合系统能有效地提高土地资源利用率,促进太阳能和有关物质在系统内的多次循环利用,实现整个系统在空间和时间上的高效利用。多年来的研究表明,这种由多种产业部     

Structural understanding of stabilization patterns in engineered bispecific Ig‐like antibody molecules

Bispecific immunoglobulin‐like antibodies capable of engaging multiple antigens represent a promising new class of therapeutic agents. Engineering of these molecules requires optimization of the molecular properties of one of the domain components. Here, we present a detailed crystallographic and computational characterization of the stabilization patterns in the lymphotoxin‐beta receptor (LTβR) binding Fv domain of an anti‐LTβR/anti‐TNF‐related apoptosis inducing ligand receptor‐2 (TRAIL‐R2) bispecific immunoglobulin‐like antibody. We further describe a new hierarchical structure‐guided approach toward engineering of antibody‐like molecules to enhance their thermal and chemical stability. Proteins 2009. © 2009 Wiley‐Liss, Inc.     

Leaf traits of natural populations of <Emphasis Type="Italic">Adiantum reniforme</Emphasis> var. <Emphasis Type="Italic">sinensis</Emphasis>, endemic to the Three Gorges region in China

Leaf mass per unit area (LMA), carbon and nitrogen contents, leaf construction cost, and photosynthetic capacity (P _max) of Adiantum reniforme var. sinensis, an endangered fern endemic to the Three Gorges region in southwest China, were compared in five populations differing in habitat such as soil moisture and irradiance. The low soil moisture and high irradiance habitat population exhibited significantly higher LMA, area-based leaf construction (CC_A), and carbon content (C_A), but lower leaf nitrogen content per unit dry mass (N_M) than the other habitat populations. The high soil moisture and low irradiance habitat populations had the lowest CC_A, but their cost/benefic ratios of CCA/P _max were similar to the medium soil moisture and irradiance habitat population due to their lower leaf P _max. Hence A. reniforme var. sinensis prefers partially shaded, moist but well-drained, slope habitats. Due to human activities, however, its main habitats now are cliffs or steeply sloped bare rocks with poor and thin soil. The relatively high energy requirements and low photosynthetic capacity in these habitats could limit the capability of the species in extending population or interspecific competition and hence increase its endangerment.     

Flexible Solar Thermal Fuel Devices: Composites of Fabric and a Photoliquefiable Azobenzene Derivative

Controllable storage and release of solar energy has always been a highlighted scientific issue for its benefit of mankind. Solar thermal fuels (STFs) supply a closed cycle and renewable energy‐storage strategy by transforming solar energy into chemical energy stored in the conformation of molecular isomers, such as cis/trans‐azobenzene, and releasing it as heat under various stimuli. Although the potential high energy density of the STFs which are based on the hybrids of azobenzene derivatives and carbon nanomaterials has been reported the solvent‐assistant charging hinders their practicability. In this study, a solid‐state STF device is designed and fabricated by compositing one photoliquefiable azobenzene (PLAZ) derivative with a flexible fabric template. The photoinduced phase transition of the PLAZ derivative enables the charging of the flexible STFs to be totally solvent‐free. Interestingly, the energy‐storage capacity (energy density ≈201 J g^?1) of flexible PLAZ STFs has been improved by the soft fabric template. The exothermic situation is monitored with one infrared camera, which shows 4 °C temperature difference between charged and discharged samples under blue light stimulus. The flexible STFs are may be used in practice as heating equipment.     

藕莲有性繁殖栽培

根据莲(Nelumbo nucifera)生物学特性,既可用藕作种进行无性繁殖,也可用种子播种进行有性繁殖。藕莲在我国有数千年的栽培历史,但素以无性系栽培。尚未见到有性繁殖栽培的报道。作者自1980年起进行了有性繁殖栽培试验。