Regulation of endothelial permeability by Src kinase signaling: vascular leakage versus transcellular transport of drugs and macromolecules

An important function of the endothelium is to regulate the transport of liquid and solutes across the semi-permeable vascular endothelial barrier. Two cellular pathways have been identified controlling endothelial barrier function. The normally restrictive paracellular pathway, which can become "leaky" during inflammation when gaps are induced between endothelial cells at the level of adherens and tight junctional complexes, and the transcellular pathway, which transports plasma proteins the size of albumin via transcytosis in vesicle carriers originating from cell surface caveolae. During non-inflammatory conditions, caveolae-mediated transport may be the primary mechanism of vascular permeability regulation of fluid phase molecules as well as lipids, hormones, and peptides that bind avidly to albumin. Src family protein tyrosine kinases have been implicated in the upstream signaling pathways that lead to endothelial hyperpermeability through both the paracellular and transcellular pathways. Endothelial barrier dysfunction not only affects vascular homeostasis and cell metabolism, but also governs drug delivery to underlying cells and tissues. In this review of the field, we discuss the current understanding of Src signaling in regulating paracellular and transcellular endothelial permeability pathways and effects on endogenous macromolecule and drug delivery.     

微生物降解芘过程中的关键细菌

【目的】探究在渤海沉积物中参与降解芘的关键细菌及他们之间潜在的相互关系。【方法】构建以芘为唯一碳源的微宇宙培养体系驯化来自渤海的表层沉积物,借助Illumina Hiseq 2500获取驯化过程中的细菌群落组成,基于CCLasso算法及相对丰度数据预测细菌之间的相互作用关系以构建微生物生态网络。【结果】30 d后芘的降解率为(67.07±2.37)%,细菌群落结构也发生了明显改变:Alphaproteobacteria、Flavobacteriia、Planctomycetia等的相对丰度明显增加,而Deltaproteobacteria、Anaerolineae及Spirochaetes等则明显减少。本研究获得一个由29个点143条边构成的微生物生态网络。分类已知的属中,Erythrobacter及Planctomyces等拥有较高的点度中心度。较强的互作关系发生在Erythrobacter与Flavobacteriaceae、Alphaproteobacteria中的未知属之间。【结论】在芘的微生物降解过程中,关键细菌之间存在紧密互作。Erythrobacter为关键细菌的代表属。     

Effects of aspirin on the development of Helicobacter pylori-induced gastric inflammation and heterotopic proliferative glands in Mongolian gerbils

Background: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti‐inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori‐induced gastritis and the development of heterotopic proliferative glands. Methods: H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E₂ (PGE₂) levels of gastric tissue were determined. Results: H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori‐induced gastritis, but alleviated H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori‐associated apoptosis but decreased H. pylori‐associated cell proliferation. In addition, the increased gastric PGE₂ levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m. Conclusions: Aspirin alleviates H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori‐induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori‐related gastric carcinogenesis.     

Characterization of neutralizing antibody responses elicited by clade A envelope immunogens derived from early transmitted viruses

The vast majority of studies with candidate immunogens based on the human immunodeficiency virus envelope (Env) have been conducted with Env proteins derived from clade B viruses isolated during chronic infection. Whether non-clade B Env protein immunogens will elicit antibodies with epitope specificities that are similar to those of antibodies elicited by clade B Envs and whether the antibodies elicited by Envs derived from early transmitted viruses will be similar to those elicited by Envs derived from viruses isolated during chronic infection are currently unknown. Here we performed immunizations with four clade A Envs, cloned directly from the peripheral blood of infected individuals during acute infection, which differed in lengths and extents of glycosylation. The antibody responses elicited by these four Envs were compared to each other and to those elicited by a well-characterized clade B Env immunogen derived from the SF162 virus, which was isolated during chronic infection. Only one clade A Env, the one with the fewer glycosylation sites, elicited homologous neutralizing antibodies (NAbs); these did not target the V1, V2, or V3 regions. In contrast, all four clade A Envs elicited anti-V3 NAbs against "easy-to-neutralize" clade B and clade A isolates, irrespective of the variable region length and extent of glycosylation of the Env used as an immunogen. These anti-V3 NAbs did not access their epitopes on homologous and heterologous clade A, or B, neutralization-resistant viruses. The length and extent of glycosylation of the variable regions on the clade A Env immunogens tested did not affect the breadth of the elicited NAbs. Our data also indicate that the development of cross-reactive NAbs against clade A viruses faces similar hurdles to the development of cross-reactive anti-clade B NAbs.     

Spatio-temporal changes in biomass carbon sinks in China’s forests from 1977 to 2008

Forests play a leading role in regional and global carbon (C) cycles. Detailed assessment of the temporal and spatial changes in C sinks/sources of China’s forests is critical to the estimation of the national C budget and can help to constitute sustainable forest management policies for climate change. In this study, we explored the spatio-temporal changes in forest biomass C stocks in China between 1977 and 2008, using six periods of the national forest inventory data. According to the definition of the forest inventory, China’s forest was categorized into three groups: forest stand, economic forest, and bamboo forest. We estimated forest biomass C stocks for each inventory period by using continuous biomass expansion factor (BEF) method for forest stands, and the mean biomass density method for economic and bamboo forests. As a result, China’s forests have accumulated biomass C (i.e., biomass C sink) of 1896 Tg (1 Tg=10¹² g) during the study period, with 1710, 108 and 78 Tg C in forest stands, and economic and bamboo forests, respectively. Annual forest biomass C sink was 70.2 Tg C a^?1, offsetting 7.8% of the contemporary fossil CO₂ emissions in the country. The results also showed that planted forests have functioned as a persistent C sink, sequestrating 818 Tg C and accounting for 47.8% of total C sink in forest stands, and that the old-, mid- and young-aged forests have sequestrated 930, 391 and 388 Tg C from 1977 to 2008. Our results suggest that China’s forests have a big potential as biomass C sink in the future because of its large area of planted forests with young-aged growth and low C density.     

Alterations in cell membrane properties caused by perfluorinated compounds

The recent detection of perfluorinated compounds (PFCs) in wildlife from even remote locations has spurred interest in the environmental occurrence and effects of these chemicals. While the global distribution of PFCs is increasingly understood, there is still little information available on their effects on wildlife. The amphiphillic nature of PFCs suggests that their effects could be primarily on cell membranes. In this study we measured the effects of PFCs on membrane fluidity and mitochondrial membrane potential using flow cytometry and effects on membrane permeability using cell bioassay procedures (H4IIE, MCF-7, PLHC-1). Of the PFCs tested, only perfluorooctane sulfonic acid (PFOS) increased the permeability of cell membranes to the hydrophobic ligands used. Three PFCs were tested in the membrane fluidity assay: PFOS, perfluorohexane sulfonic acid (PFHS), and perfluorobutane sulfonic acid (PFBS). PFOS increased membrane fluidity in fish leukocytes in a dose-dependent fashion, while PFHS and PFBS had no effect in the concentration range tested. The lowest effective concentrations for the membrane fluidity effects of PFOS were 5-15 mg/l. Effects on mitochondrial membrane potential occurred in the same concentration range as effects on membrane fluidity. This suggests that PFOS effects membrane properties at concentrations below those associated with other adverse effects.     

Succession of aquatic macrophytes in the Modern Yellow River Delta after 150 years of alluviation

This study evaluated the succession process of aquatic macrophytes after 150 years of alluviation in the Modern Yellow River Delta, China, and identified the roles of various environmental parameters that regulate vegetation succession. From 2007 to 2008, 214 quadrats were surveyed and 19 environmental parameters were measured, including elevation, plot distance from the seashore, 10 water parameters, and 7 soil parameters. Forty-six aquatic macrophytes belonging to 20 families and 34 genera were identified across the entire delta. Emergent and submerged plants were the most frequent species, accounting for 58.7 and 34.8 % of all species, respectively. Detrended canonical correspondence analysis showed that the presence of aquatic macrophytes in this delta was primarily regulated by water salinity, soil salinity, and distance from the seashore, followed by nutrient concentrations (e.g., NH₄ ⁺, total soil N and PO₄ ^? of water). Salinity-tolerant species (e.g., Ruppia maritima, Phragmites australis, and Typha angustifolia) tended to be widely distributed across the entire delta. In contrast, salinity-sensitive species (e.g., Ceratophyllum demersum, Hydrilla verticillata, and Potamogeton malaianus) tended to be distributed in areas at the early stages of succession, which were relatively distant from the shore. Moreover, this study also confirmed that species richness and diversity were negatively correlated with water and soil salinity, which in turn were negatively correlated with plot distance from the shore. These data indicate that the primary drivers of aquatic macrophyte succession in this delta are water and soil salinity. The information assimilated here is used to propose management practices for the protection of aquatic macrophytes in the Yellow River Delta.     

Approximating subject-specific brain injury models via scaling based on head–brain morphological relationships

Biomechanics and Modeling in Mechanobiology - Most human head/brain models represent a generic adult male head/brain. They may suffer in accuracy when investigating traumatic brain injury (TBI) on...