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1.
Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice.  相似文献   
2.
目的:研究混合效应模型(Mixed Effects Model)在肿瘤表达谱基因芯片数据分析中的检验效能,并探讨其分析效果。方法:采用混合效应模型分析肿瘤实例基因芯片数据,并以基因集富集分析方法(GSEA)作为参照比较分析结果的有效性和科学性,探讨其检验效果。结果:通过混合效应模型和基因集富集分析(GSEA)两种方法对肿瘤基因芯片数据的分析和比较,两种方法筛选出共同的差异表达通路外,混合效应模型额外地筛选出来GSEA未能检验到的8条差异表达通路,且得到文献支持;混和效应模型筛选出的前10个差异表达通路中有6个已有生物学证明而基因集富集分析方法(GSEA)筛选出的前10个差异表达通路中仅有4个已有生物学证明。结论:混合效应模型作为top-down方法中的典型代表,其优势在于通过构建潜变量达到降维目的,可有效地减少多个复杂的变异来源从而保证了结果的准确性和科学性,其检验效能优于基因集富集分析方法(GSEA),是一种行之有效的筛选肿瘤基因芯片数据的分析方法。  相似文献   
3.
Since Gleason and Clements, our understanding of community dynamics has been influenced by theories emphasising either dispersal or niche assembly as central to community structuring. Determining the relative importance of these processes in structuring real‐world communities remains a challenge. We tracked reef fish community reassembly after a catastrophic coral mortality in a relatively unfished archipelago. We revisited the stochastic model underlying MacArthur and Wilson's Island Biogeography Theory, with a simple extension to account for trophic identity. Colonisation and extinction rates calculated from decadal presence‐absence data based on (1) species neutrality, (2) trophic identity and (3) site‐specificity were used to model post‐disturbance reassembly, and compared with empirical observations. Results indicate that species neutrality holds within trophic guilds, and trophic identity significantly increases overall model performance. Strikingly, extinction rates increased clearly with trophic position, indicating that fish communities may be inherently susceptible to trophic downgrading even without targeted fishing of top predators.  相似文献   
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In the study of food webs, the existence and explanation of recurring patterns, such as the scale invariance of linkage density, predator–prey ratios and mean chain length, constitute long-standing issues. Our study focused on litter-associated food webs and explored the influence of detritivore and predator niche width (as δ13C range) on web topological structure. To compare patterns within and between aquatic and terrestrial ecosystems and take account of intra-habitat variability, we constructed 42 macroinvertebrate patch-scale webs in four different habitats (lake, lagoon, beech forest and cornfield), using an experimental approach with litterbags. The results suggest that although web differences exist between ecosystems, patterns are more similar within than between aquatic and terrestrial web types. In accordance with optimal foraging theory, we found that the niche width of predators and prey increased with the number of predators and prey taxa as a proportion of total taxa in the community. The tendency was more marked in terrestrial ecosystems and can be explained by a lower per capita food level than in aquatic ecosystems, particularly evident for predators. In accordance with these results, the number of links increased with the number of species but with a significantly sharper regression slope for terrestrial ecosystems. As a consequence, linkage density, which was found to be directly correlated to niche width, increased with the total number of species in terrestrial webs, whereas it did not change significantly in aquatic ones, where connectance scaled negatively with the total number of species. In both types of ecosystem, web robustness to rare species removal increased with connectance and the niche width of predators. In conclusion, although limited to litter-associated macroinvertebrate assemblages, this study highlights structural differences and similarities between aquatic and terrestrial detrital webs, providing field evidence of the central role of niche width in determining the structure of detritus-based food webs and posing foraging optimisation constraints as a general mechanistic explanation of food web complexity differences within and between ecosystem types.  相似文献   
7.
It is known that over half of the proteins encoded by most organisms function as oligomeric complexes. Oligomerization confers structural stability and dynamics changes in proteins. We investigate the effects of oligomerization on protein dynamics and its functional significance for a set of 145 multimeric proteins. Using coarse‐grained elastic network models, we inspect the changes in residue fluctuations upon oligomerization and then compare with residue conservation scores to identify the functional significance of these changes. Our study reveals conservation of about ½ of the fluctuations, with ¼ of the residues increasing in their mobilities and ¼ having reduced fluctuations. The residues with dampened fluctuations are evolutionarily more conserved and can serve as orthosteric binding sites, indicating their importance. We also use triosephosphate isomerase as a test case to understand why certain enzymes function only in their oligomeric forms despite the monomer including all required catalytic residues. To this end, we compare the residue communities (groups of residues which are highly correlated in their fluctuations) in the monomeric and dimeric forms of the enzyme. We observe significant changes to the dynamical community architecture of the catalytic core of this enzyme. This relates to its functional mechanism and is seen only in the oligomeric form of the protein, answering why proteins are oligomeric structures. Proteins 2017; 85:1422–1434. © 2017 Wiley Periodicals, Inc.  相似文献   
8.
A new homology model of human microsomal epoxide hydrolase was derived based on multiple templates. The model obtained was fully evaluated, including MD simulations and ensemble‐based docking, showing that the quality of the structure is better than that of only previously known model. Particularly, a catalytic triad was clearly identified, in agreement with the experimental information available. Analysis of intermediates in the enzymatic mechanism led to the identification of key residues for substrate binding, stereoselectivity, and intermediate stabilization during the reaction. In particular, we have confirmed the role of the oxyanion hole and the conserved motif (HGXP) in epoxide hydrolases, in excellent agreement with known experimental and computational data on similar systems. The model obtained is the first one that fully agrees with all the experimental observations on the system. Proteins 2017; 85:720–730. © 2016 Wiley Periodicals, Inc.  相似文献   
9.
In this paper we analyze a model for the HIV-infection transmission in a male homosexual population. In the model we consider two types of infected individuals. Those that are infected but do not know their serological status and/or are not under any sort of clinical /therapeutical treatment, and those who are. The two groups of infectives differ in their incubation time, contact rate with susceptible individuals, and probability of disease transmission. The aim of this article is to study the roles played by detection and changes in sexual behavior in the incidence and prevalence of HIV. The analytical results show that there exists a unique endemic equilibrium which is globally asymptotically stable under a range of parameter values whenever a detection /treatment rate and an indirect measure of the level of infection risk are sufficiently large. However, any level of detection/ treatment rate coupled with a decrease of the transmission probability lowers the incidence rate and prevalence level in the population. In general, only significant reductions in the transmission probability (achieved through, for example, the adoption of safe sexual practices) can contain effectively the spread of the disease.  相似文献   
10.
Prospective life cycle assessment (LCA) needs to deal with the large epistemological uncertainty about the future to support more robust future environmental impact assessments of technologies. This study proposes a novel approach that systematically changes the background processes in a prospective LCA based on scenarios of an integrated assessment model (IAM), the IMAGE model. Consistent worldwide scenarios from IMAGE are evaluated in the life cycle inventory using ecoinvent v3.3. To test the approach, only the electricity sector was changed in a prospective LCA of an internal combustion engine vehicle (ICEV) and an electric vehicle (EV) using six baseline and mitigation climate scenarios until 2050. This case study shows that changes in the electricity background can be very important for the environmental impacts of EV. Also, the approach demonstrates that the relative environmental performance of EV and ICEV over time is more complex and multifaceted than previously assumed. Uncertainty due to future developments manifests in different impacts depending on the product (EV or ICEV), the impact category, and the scenario and year considered. More robust prospective LCAs can be achieved, particularly for emerging technologies, by expanding this approach to other economic sectors beyond electricity background changes and mobility applications as well as by including uncertainty and changes in foreground parameters. A more systematic and structured composition of future inventory databases driven by IAM scenarios helps to acknowledge epistemological uncertainty and to increase the temporal consistency of foreground and background systems in LCAs of emerging technologies.  相似文献   
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