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目的:静脉血栓是一种高复发风险和高致死率的疾病,其形成和复发的分子机制尚不明确。基于人类信号网络和基因表达谱数据可针对静脉血栓经华法令抗凝治疗后的复发机制进行研究。方法:结合表达谱数据和人类信号网络,设计差异模块筛选策略,通过功能分析、差异表达分析和已知血栓相关基因及药物靶基因的互作关联研究,获得与静脉血栓复发相关的显著差异模块。结果:最终获得8个与静脉血栓复发密切相关的显著差异模块,评估了华法令治疗静脉血栓的效能,提出了联合用药的3种可能途径。结论:应用本文提出的整合筛选策略,能识别与静脉血栓复发相关的模块,探究静脉血栓复发的分子机制和评估华法令的治疗效能。还提供了潜在的联合用药途径,这对治愈血栓、防治血栓复发及复发机制的研究具有重要意义。 相似文献
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Habitat destruction is driving biodiversity loss in remaining ecosystems, and ecosystem functioning and services often directly depend on biodiversity. Thus, biodiversity loss is likely creating an ecosystem service debt: a gradual loss of biodiversity‐dependent benefits that people obtain from remaining fragments of natural ecosystems. Here, we develop an approach for quantifying ecosystem service debts, and illustrate its use to estimate how one anthropogenic driver, habitat destruction, could indirectly diminish one ecosystem service, carbon storage, by creating an extinction debt. We estimate that c. 2–21 Pg C could be gradually emitted globally in remaining ecosystem fragments because of plant species loss caused by nearby habitat destruction. The wide range for this estimate reflects substantial uncertainties in how many plant species will be lost, how much species loss will impact ecosystem functioning and whether plant species loss will decrease soil carbon. Our exploratory analysis suggests that biodiversity‐dependent ecosystem service debts can be globally substantial, even when locally small, if they occur diffusely across vast areas of remaining ecosystems. There is substantial value in conserving not only the quantity (area), but also the quality (biodiversity) of natural ecosystems for the sustainable provision of ecosystem services. 相似文献
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Margaret S. Robinson 《Traffic (Copenhagen, Denmark)》2015,16(12):1210-1238
The purification of coated vesicles and the discovery of clathrin by Barbara Pearse in 1975 was a landmark in cell biology. Over the past 40 years, work from many labs has uncovered the molecular details of clathrin and its associated proteins, including how they assemble into a coated vesicle and how they select cargo. Unexpected connections have been found with signalling, development, neuronal transmission, infection, immunity and genetic disorders. But there are still a number of unanswered questions, including how clathrin‐mediated trafficking is regulated and how the machinery evolved. 相似文献
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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
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Nathalie Isabelle Chardon Samuel Pironon Megan Lynn Peterson Daniel Forest Doak 《Ecography》2020,43(1):60-74
The most common approach to predicting how species ranges and ecological functions will shift with climate change is to construct correlative species distribution models (SDMs). These models use a species’ climatic distribution to determine currently suitable areas for the species and project its potential distribution under future climate scenarios. A core, rarely tested, assumption of SDMs is that all populations will respond equivalently to climate. Few studies have examined this assumption, and those that have rarely dissect the reasons for intraspecific differences. Focusing on the arctic-alpine cushion plant Silene acaulis, we compared predictive accuracy from SDMs constructed using the species’ full global distribution with composite predictions from separate SDMs constructed using subpopulations defined either by genetic or habitat differences. This is one of the first studies to compare multiple ways of constructing intraspecific-level SDMs with a species-level SDM. We also examine the contested relationship between relative probability of occurrence and species performance or ecological function, testing if SDM output can predict individual performance (plant size) and biotic interactions (facilitation). We found that both genetic- and habitat-informed SDMs are considerably more accurate than a species-level SDM, and that the genetic model substantially differs from and outperforms the habitat model. While SDMs have been used to infer population performance and possibly even biotic interactions, in our system these relationships were extremely weak. Our results indicate that individual subpopulations may respond differently to climate, although we discuss and explore several alternative explanations for the superior performance of intraspecific-level SDMs. We emphasize the need to carefully examine how to best define intraspecific-level SDMs as well as how potential genetic, environmental, or sampling variation within species ranges can critically affect SDM predictions. We urge caution in inferring population performance or biotic interactions from SDM predictions, as these often-assumed relationships are not supported in our study. 相似文献