Feedback regulation of coronary artery disease susceptibility gene ADTRP and LDL receptors LDLR/CD36/LOX-1 in endothelia cell functions involved in atherosclerosis

A high level of low-density lipoprotein cholesterol (LDL) is one of the most important risk factors for coronary artery disease (CAD), the leading cause of death worldwide. However, a low concentration of LDL may be protective. Genome-wide association studies revealed that variation in ADTRP gene increased the risk of CAD. In this study, we found that a low concentration of oxidized-LDL induced the expression of ADTRP. Further analyses showed that knockdown of the expression of LDL receptor genes LDLR, CD36, or LOX-1 significantly downregulated ADTRP expression, whereas overexpression of LDLR/CD36/LOX-1 markedly increased ADTRP expression through the NF-κB pathway. Like ADTRP, LDLR, CD36 and LOX-1 were all involved in endothelial cell (EC) functions relevant to the initiation of atherosclerosis. Downregulation of LDLR/CD36/LOX-1 promoted monocyte adhesion to ECs and transendothelial migration of monocytes by increasing expression of ICAM-1, VCAM-1, E-selectin and P-selectin, decreased EC proliferation and migration, and increased EC apoptosis, thereby promoting the initiation of atherosclerosis. Opposite effects were observed with the overexpression of ADTRP and LDLR/CD36/LOX-1 in ECs. Interestingly, through the NF-κB and AKT pathways, overexpression of ADTRP significantly upregulated the expression of LDLR, CD36, and LOX-1, and knockdown of ADTRP expression significantly downregulated the expression of LDLR, CD36, and LOX-1. These data suggest that ADTRP and LDL receptors LDLR/CD36/LOX-1 positively regulate each other, and form a positive regulatory loop that regulates endothelial cell functions, thereby providing a potential protective mechanism against atherosclerosis. Our findings provide a new molecular mechanism by which deregulation of ADTRP and LDLR/CD36/LOX-1 promote the development of atherosclerosis and CAD.     

Characterizing the impacts of highway pavement in a newly planned greater bay area economic belt in China

The International Journal of Life Cycle Assessment - As an ambitious strategy of national interest in China and with an aim at achieving the ‘one-hour economic circle’ among Greater Bay...     

Divergent DNA methylation contributes to duplicated gene evolution and chilling response in tea plants

The tea plant (Camellia sinensis) is a thermophilic cash crop and contains a highly duplicated and repeat-rich genome. It is still unclear how DNA methylation regulates the evolution of duplicated genes and chilling stress in tea plants. We therefore generated a single-base-resolution DNA methylation map of tea plants under chilling stress. We found that, compared with other plants, the tea plant genome is highly methylated in all three sequence contexts, including CG, CHG and CHH (where H = A, T, or C), which is further proven to be correlated with its repeat content and genome size. We show that DNA methylation in the gene body negatively regulates the gene expression of tea plants, whereas non-CG methylation in the flanking region enables a positive regulation of gene expression. We demonstrate that transposable element-mediated methylation dynamics significantly drives the expression divergence of duplicated genes in tea plants. The DNA methylation and expression divergence of duplicated genes in the tea plant increases with evolutionary age and selective pressure. Moreover, we detect thousands of differentially methylated genes, some of which are functionally associated with chilling stress. We also experimentally reveal that DNA methyltransferase genes of tea plants are significantly downregulated, whereas demethylase genes are upregulated at the initial stage of chilling stress, which is in line with the significant loss of DNA methylation of three well-known cold-responsive genes at their promoter and gene body regions. Overall, our findings underscore the importance of DNA methylation regulation and offer new insights into duplicated gene evolution and chilling tolerance in tea plants.     

Stromal cell‐derived factor‐1/Exendin‐4 cotherapy facilitates the proliferation,migration and osteogenic differentiation of human periodontal ligament stem cells in vitro and promotes periodontal bone regeneration in vivo

ObjectivesStromal cell‐derived factor‐1 (SDF‐1) actively directs endogenous cell homing. Exendin‐4 (EX‐4) promotes stem cell osteogenic differentiation. Studies revealed that EX‐4 strengthened SDF‐1‐mediated stem cell migration. However, the effects of SDF‐1 and EX‐4 on periodontal ligament stem cells (PDLSCs) and bone regeneration have not been investigated. In this study, we aimed to evaluate the effects of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro and periodontal bone regeneration in vivo.MethodsCell‐counting kit‐8 (CCK8), transwell assay, qRT‐PCR and western blot were used to determine the effects and mechanism of SDF‐1/EX‐4 cotherapy on PDLSCs in vitro. A rat periodontal bone defect model was developed to evaluate the effects of topical application of SDF‐1 and systemic injection of EX‐4 on endogenous cell recruitment, osteoclastogenesis and bone regeneration in vivo.ResultsSDF‐1/EX‐4 cotherapy had additive effects on PDLSC proliferation, migration, alkaline phosphatase (ALP) activity, mineral deposition and osteogenesis‐related gene expression compared to SDF‐1 or EX‐4 in vitro. Pretreatment with ERK inhibitor U0126 blocked SDF‐1/EX‐4 cotherapy induced ERK signal activation and PDLSC proliferation. SDF‐1/EX‐4 cotherapy significantly promoted new bone formation, recruited more CXCR4⁺ cells and CD90⁺/CD34^‐ stromal cells to the defects, enhanced early‐stage osteoclastogenesis and osteogenesis‐related markers expression in regenerated bone compared to control, SDF‐1 or EX‐4 in vivo.ConclusionsSDF‐1/EX‐4 cotherapy synergistically regulated PDLSC activities, promoted periodontal bone formation, thereby providing a new strategy for periodontal bone regeneration.     

Application of plant metabarcoding to identify diverse honeybee pollen forage along an urban–agricultural gradient

Understanding animal foraging ecology requires large sample sizes spanning broad environmental and temporal gradients. For pollinators, this has been hampered by the laborious nature of morphologically identifying pollen. Identifying pollen from urban environments is particularly difficult due to the presence of diverse ornamental species associated with consumer horticulture. Metagenetic pollen analysis represents a potential solution to this issue. Building upon prior laboratory and bioinformatic methods, we applied quantitative multilocus metabarcoding to characterize the foraging ecology of honeybee colonies situated in urban, suburban, mixed suburban–agricultural and rural agricultural sites in central Ohio, USA. In cross‐validating a subset of our metabarcoding results using microscopic palynology, we find strong concordance between the molecular and microscopic methods. Our results suggest that forage from the agricultural site exhibited decreased taxonomic diversity and temporal turnover relative to the urban and suburban sites, though the generalization of this observation will require replication across additional sites and cities. Our work demonstrates the power of honeybees as environmental samplers of floral community composition at large spatial scales, aiding in the distinction of taxa characteristically associated with urban or agricultural land use from those distributed ubiquitously across the sampled landscapes. Observed patterns of high forage diversity and compositional turnover in our more urban sites are likely reflective of the fine‐grain heterogeneity and high beta diversity of urban floral landscapes at the scale of honeybee foraging. This provides guidance for future studies investigating how relationships between urbanization and measures of pollinator health are mediated by variation in floral resource dynamics across landscapes.     

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/ .     

中国退耕还林还草对生态系统服务权衡与协同的影响

基于生态系统服务之间相关关系的时空动态变化,实现区域可持续发展与生态系统利益最大化,是兼顾生态保护、粮食安全、改善民生等多目标的重要途径。通过分析退耕还林还草工程县域粮食供给与地块水源涵养、土壤保持、防风固沙功能变化,评估退耕还林还草工程对生态系统关键服务之间权衡与协同关系的影响。结果表明：（1）2000-2015年,约76%工程县域的粮食供给增加,约46%和49%工程县域退耕还林还草地块的土壤保持与水源涵养功能呈提升态势,而风蚀区仅约2%工程县域的地块防风固沙功能明显提升。（2）1897个工程县域中,约24%县域粮食供给与地块水源涵养、约18%县域粮食供给与地块土壤保持之间呈显著地空间协同关系,风蚀区约38%县域粮食供给与地块防风固沙之间呈显著地空间权衡关系。（3）31%工程县域表现为多重生态系统服务供给区,其中双重服务供给县域占43%,三重服务供给县域占53%,四重服务供给县域占4%。（4）近16年,不同区域退耕还林还草工程导致粮食供给与调节服务之间呈现权衡与协同相互转换、权衡或协同程度变化等差异的空间相关关系,反映了多重生态系统服务联合权衡与协同在未来工程生态效应评估中的重要性。     

南水北调中线水源区丹江口市域景观格局变化及氮磷净化能力

丹江口库区是南水北调中线工程重要水源地,通过探究库区景观格局变化与氮磷净化能力,对未来景观规划和生态系统功能提升提供科学依据。在县域尺度上以丹江口市为研究区,运用景观格局指数和InVEST模型研究2003—2018年库区景观格局和氮磷净化能力,并利用Pearson相关分析和RDA分析法探讨二者之间的关系,分析引起氮磷净化能力变化的因素。结果表明:在斑块类型上,水域面积和林地面积不断增加,耕地和园地面积逐渐减少,建设用地面积整体上呈增长趋势;在景观水平上,景观形状指数不断减少,蔓延度指数和聚集度指数整体呈增长趋势,形状复杂程度降低,景观聚集程度提升,散布与并列指数增加了5.58,香农多样性指数变幅较小,各斑块类型趋于规则,呈均衡趋势分布。2003年、2008年、2013年和2018年氮磷净化能力呈持续增强趋势,其中TN输出总量分别为899.224、801.481、776.979、672.149 t, TP输出总量分别为77.308、69.921、68.163、60.802 t, 15年间TN、TP的净化能力分别增强了25.3%和21.4%;对氮磷净化能力重要性等级划分表明,极重要、高度重要区主要分布于库区、河流两岸和林地区域。利用Pearson相关分析和RDA分析法表明,在斑块类型上林地与氮磷的输出呈显著负相关,耕地、园地和建设用地与氮磷输出量呈正相关;在景观水平上氮磷输出量与景观形状指数呈显著正相关,和散布与并列指数表现出显著负相关,与蔓延度指数、聚集度指数呈负相关。因此,可在库区氮磷输出量较高的地区种植喜氮喜磷植物,通过调节景观格局结构,合理规划土地利用,增加林地面积,建设河岸植被缓冲带充分滞缓径流等一系列措施,充分保障库区水源水质安全。