甘草抗动脉粥样硬化机制的网络药理学研究

利用网络药理学方法探讨甘草在抗动脉粥样硬化中的分子机制。本研究利用中医药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)分析甘草中的有效活性成分,并获得有效成分的作用靶点。通过Cytoscape软件构建可视化靶点互相作用网络,对网络中的关键靶点进行基因本体(GO)富集分析和KEGG通路富集分析。结果显示甘草中40种有效活性成分的预测靶点共97个,47个靶点与动脉粥样硬化(AS)相关,其中18个是血管保护药物和脂质修饰药物的作用靶点,表明甘草可作为调控AS发展的药物。基于97个预测靶点的GO富集分析,发现甘草可参与多种生物学过程,尤其是应对外源性刺激,以及参与细胞凋亡等过程。通过构建甘草靶点与AS疾病靶点相互作用网络(PPI),确定了AKT1、MAPK3、MAPK1、JUN和CASP3等关键靶点,并对关键靶点进行KEGG富集分析,结果表明甘草主要影响调控细胞增殖、生存以及凋亡的细胞信号转导相关通路,并激活先天免疫相关信号通路,调节炎性细胞因子释放,从而发挥抗动脉粥样硬化作用。甘草具有多成分、多靶点、多途径的作用特点,主要通过PI3K-AKT信号途径、MAPK信号途径、NOD样受体信号通路调控细胞增殖和凋亡,同时发挥免疫调控作用,从而影响动脉粥样硬化的发展,由此可见,甘草可作为动脉粥样硬化疾病治疗的候选中草药。     

Trophic niche similarities of sympatric Turdus thrushes determined by fecal contents,stable isotopes,and bipartite network approaches

An ecological niche has been defined as an n‐dimensional hypervolume formed by conditions and resources that species need to survive, grow, and reproduce. In practice, such niche dimensions are measurable and describe how species share resources, which has been thought to be a crucial mechanism for coexistence and a major driver of broad biodiversity patterns. Here, we investigate resource partitioning and trophic interactions of three sympatric, phylogenetically related and morphologically similar species of thrushes (Turdus spp.). Based on one year of data collected in southern Brazil, we investigated niche partitioning using three approaches: diet and trophic niche assessed by fecal analysis, diet and niche estimated by stable isotopes in blood and mixing models, and bipartite network analysis derived from direct diet and mixing model outputs. Approaches revealed that the three sympatric thrushes are generalists that feed on similar diets, demonstrating high niche overlap. Fruits from C3 plants were one of the most important food items in their networks, with wide links connecting the three thrush species. Turdus amaurochalinus and T. albicollis had the greatest trophic and isotopic niche overlap, with 90% and 20% overlap, respectively. There was partitioning of key resources between these two species, with a shared preference for fig tree fruits—Ficus cestrifolia (T. amaurochalinus PSIRI% = 11.3 and T. albicollis = 11.5), which was not present in the diet of T. rufiventris. Results added a new approach to the network analysis based on values from the stable isotope mixing models, allowing comparisons between traditional dietary analysis and diet inferred by isotopic mixing models, which reflects food items effectively assimilated in consumer tissues. Both are visualized in bipartite networks and show food‐consumers link strengths. This approach could be useful to other studies using stable isotopes coupled to network analysis, particularly useful in sympatric species with similar niches.     

Robustness of a meta-network to alternative habitat loss scenarios

Studying how habitat loss affects the tolerance of ecological networks to species extinction (i.e. their robustness) is key for our understanding of the influence of human activities on natural ecosystems. With networks typically occurring as local interaction networks interconnected in space (a meta-network), we may ask how the loss of specific habitat fragments affects the overall robustness of the meta-network. To address this question, for an empirical meta-network of plants, herbivores and natural enemies we simulated the removal of habitat fragments in increasing and decreasing order of area, age and connectivity for plant extinction and the secondary extinction of herbivores, natural enemies and their interactions. Meta-network robustness was characterized as the area under the curve of remnant species or interactions at the end of a fragment removal sequence. To pinpoint the effects of fragment area, age and connectivity, respectively, we compared the observed robustness for each removal scenario against that of a random sequence. The meta-network was more robust to the loss of old (i.e. long-fragmented), large, connected fragments than of young (i.e. recently fragmented), small, isolated fragments. Thus, young, small, isolated fragments may be particularly important to the conservation of species and interactions, while contrary to our expectations larger, more connected fragments contribute little to meta-network robustness. Our findings highlight the importance of young, small, isolated fragments as sources of species and interactions unique to the regional level. These effects may largely result from an unpaid extinction debt, whereby younger fragments are likely to lose species over time. Yet, there may also be more long-lasting effects from cultivated lands (e.g. water, fertilizers and restricted cattle grazing) and network complexity in small, isolated fragments. Such fragments may sustain important biological diversity in fragmented landscapes, but maintaining their conservation value may depend on adequate restoration strategies.     

Integrated analysis of ceRNA network and tumor-infiltrating immune cells in esophageal cancer

Background: Esophageal cancer (ESCA) is one of the most commonly diagnosed cancers in the world. Tumor immune microenvironment is closely related to tumor prognosis. The present study aimed at analyzing the competing endogenous RNA (ceRNA) network and tumor-infiltrating immune cells in ESCA.Methods: The expression profiles of mRNAs, lncRNAs, and miRNAs were downloaded from the Cancer Genome Atlas database. A ceRNA network was established based on the differentially expressed RNAs by Cytoscape. CIBERSORT was applied to estimate the proportion of immune cells in ESCA. Prognosis-associated genes and immune cells were applied to establish prognostic models basing on Lasso and multivariate Cox analyses. The survival curves were constructed with Kaplan–Meier method. The predictive efficacy of the prognostic models was evaluated by the receiver operating characteristic (ROC) curves.Results: The differentially expressed mRNAs, lncRNAs, and miRNAs were identified. We constructed the ceRNA network including 23 lncRNAs, 19 miRNAs, and 147 mRNAs. Five key molecules (HMGB3, HOXC8, HSPA1B, KLHL15, and RUNX3) were identified from the ceRNA network and five significant immune cells (plasma cells, T cells follicular helper, monocytes, dendritic cells activated, and neutrophils) were selected via CIBERSORT. The ROC curves based on key genes and significant immune cells all showed good sensitivity (AUC of 3-year survival: 0.739, AUC of 5-year survival: 0.899, AUC of 3-year survival: 0.824, AUC of 5-year survival: 0.876). There was certain correlation between five immune cells and five key molecules.Conclusion: The present study provides an effective bioinformatics basis for exploring the potential biomarkers of ESCA and predicting its prognosis.     

The Bio3D packages for structural bioinformatics

Bio3D is a family of R packages for the analysis of biomolecular sequence, structure, and dynamics. Major functionality includes biomolecular database searching and retrieval, sequence and structure conservation analysis, ensemble normal mode analysis, protein structure and correlation network analysis, principal component, and related multivariate analysis methods. Here, we review recent package developments, including a new underlying segregation into separate packages for distinct analysis, and introduce a new method for structure analysis named ensemble difference distance matrix analysis (eDDM). The eDDM approach calculates and compares atomic distance matrices across large sets of homologous atomic structures to help identify the residue wise determinants underlying specific functional processes. An eDDM workflow is detailed along with an example application to a large protein family. As a new member of the Bio3D family, the Bio3D‐eddm package supports both experimental and theoretical simulation‐generated structures, is integrated with other methods for dissecting sequence‐structure–function relationships, and can be used in a highly automated and reproducible manner. Bio3D is distributed as an integrated set of platform independent open source R packages available from: http://thegrantlab.org/bio3d/ .     

Strategic Habitat Conservation for Beach Mice: Estimating Management Scenario Efficiencies

The Perdido Key beach mouse (Peromyscus polionotus trissyllepsis), Choctawhatchee beach mouse (P. p. allophrys), and St. Andrew beach mouse (P. p. peninsularis) are 3 federally endangered subspecies that inhabit coastal dunes of Alabama and Florida, USA. Conservation opportunities for these subspecies are limited and costly. Consequently, well-targeted efforts are required to achieve their downlisting criteria. To aid the development of targeted management scenarios that are designed to achieve downlisting criteria, we developed a Bayesian network model that uses habitat characteristics to predict the probability of beach mouse presence at a 30-m resolution across a portion of the Florida Panhandle. We then designed alternative management scenarios for a variety of habitat conditions for coastal dunes. Finally, we estimated how much area is needed to achieve the established downlisting criterion (i.e., habitat objective) and the amount of effort needed to achieve the habitat objective (i.e., management efficiency). The results suggest that after 7 years of post-storm recolonization, habitat objectives were met for Perdido Key (within its Florida critical habitat) and Choctawhatchee beach mice. The St. Andrew beach mouse required 5.14 km² of additional critical habitat to be protected and occupied. The St. Andrew beach mouse habitat objective might be achieved by first restoring protected critical habitat to good dune conditions and then protecting or restoring the unprotected critical habitat with the highest predicted probability of beach mouse presence. This scenario provided a 28% increase in management efficiency compared to a scenario that randomly protected or restored undeveloped unprotected critical habitat. In total, when coupled with established downlisting criteria, these quantitative and spatial decision support tools could provide insight into how much habitat is available, how much more is needed, and targeted conservation or restoration efforts that might efficiently achieve habitat objectives. © 2020 The Wildlife Society.