Identification of a new small molecule chemotype of Melanin Concentrating Hormone Receptor-1 antagonists using pharmacophore-based virtual screening

MCH receptor is a G protein-coupled receptor with two subtypes R1 and R2. Many studies have demonstrated the role of MCH-R1 in feeding and energy homeostasis. It has been proven that oral administration of small molecule MCH-R1 antagonists significantly reduces food intake and causes a dose-dependent weight loss. In this study, two ligand-based pharmacophores were developed and validated based on recently published MCH-R1 antagonists with diverse structures. Successful pharmacophores had one hydrogen bond acceptor, one positive ionizable, one ring aromatic and two or three hydrophobic groups. These 3D-QSAR models were used for virtual screening of the ZINC chemical database resulting in the identification of nine compounds with more than 50% displacement of radiolabeled MCH at a 20 μM concentration. Moreover, four of these compounds showed antagonistic activities in Aequorin functional assay, including MH-3 which is the first MCH-R1 antagonist based on a diazaspiro[4.5]decane scaffold. The most active compounds were also docked into our previously published MCH-R1 homology model to gain insights into their binding determinants. These compounds could represent a viable starting scaffold for the design of potent MCH-R1 antagonists with improved pharmacokinetic properties as an effective treatment for obesity.     

高速公路生态景观质量评价指标体系和评价方法:以江苏南通为例

公路生态景观建设不仅是公路建设的重要组成部分,也是美丽乡村建设和生态园林城市建设的重要标志,对于实现社会经济的可持续发展具有重要作用.公路生态景观质量的评价指标和方法是衡量公路及其外部环境建设质量的重要依据.本研究以江苏省南通市5条主要干线高速公路G15、G228、G204、S334和S335为例,建立了定量和定性评价指标相结合的公路生态景观质量评价指标体系,包括景观功能、生态效能和安全设计3大类12个评价指标.通过现场调查和计算,建立了12个评价指标的变量矩阵,并进行了主成分(PC)分析.结果表明: 公路绿化景观生态评价综合得分模型为: H=0.694PC1+0.191PC2+0.115PC3, 5条高速公路得分排序结果为: G204>G15>S334>G228>S335.本研究结果将为高速公路生态景观质量评价提供方法和参考.     

基于土地利用变化情景的城市暴雨洪涝灾害风险评估——以深圳市茅洲河流域为例

近年来频发的暴雨洪涝成为威胁城市可持续发展的主要灾害类型,而土地利用变化改变了区域原有的景观结构和水文过程,是城市暴雨洪涝灾害风险加剧的重要诱因,定量探讨土地利用变化对暴雨洪涝灾害及其风险影响具有重要意义。以深圳市茅洲河流域为例,基于CLUE-S模型、SCS模型及等体积淹没算法等,对12种暴雨洪涝致灾-土地利用承灾情景下的城市暴雨洪涝灾害风险进行定量模拟。研究结果显示,相同土地利用空间格局下城市暴雨洪涝灾害随暴雨致灾危险性增加风险加剧显著;在同等致灾危险性水平下随建设用地面积增加,中等风险和高风险区面积均呈现较为明显的增加趋势,中、高风险区面积与建设用地面积的增加率表现出较高的协同变化特征;以50年遇危险性水平为例,随着建设用地面积由基期的15368.85hm~2增加至近期16076.07hm~2和远期16750.89hm~2,高风险区面积由254.07hm~2增加至276.48hm~2和286.2hm~2。由此可见,尽管暴雨强度的增加是城市暴雨洪涝灾害风险加剧的根本诱因,但是以建设用地面积增加为表征的土地利用变化对暴雨洪涝灾害风险的影响不容忽视。     

基于电子地图兴趣点数据的城市可持续发展水平分析——以绍兴市为例

在当前大数据时代背景下,电子地图兴趣点(POI,Point of Interest)作为地理空间大数据的重要类型,能直接反映城市人口密度、发展程度与强度等各类型要素的聚集状况。基于当前普遍使用的兴趣点数据源,运用ArcGIS软件中的空间分析工具,提取了绍兴市各区(县、市)的POI数据分类信息;结合绍兴市各区(县、市)的面积及人口数据,评估各区(县、市)的单位面积POI和单位人口POI指标,以分析绍兴市各区(县、市)POI的均衡分布水平。进一步利用核密度分析、空间回归分析和近邻分析的手段,从不同角度研究了各类POI在地理空间分布中的特征规律。研究结果表明:从不同区县来看,城市化发展水平较高的地域POI总数明显较高,其核函数密度值也明显较大;从单位面积POI数量及单位人口POI数量来看,各区县发展水平较不均衡,表现为越城区最高,上虞区、柯桥区和诸暨市次之,新昌县和嵊州市较低,其表现在不同区县在提供生活、生产服务的基础设施具有区域间差异性,不符合可持续发展的公平性原则。最后,针对解决这一问题提出一些促进绍兴各区县协调公平可持续发展的城市建设与规划建议。     

济南市森林生态系统服务功能的维持机制

森林作为陆地生态系统的重要组成部分,在维持生物多样性、固碳、水源涵养和木材供应等方面起着不可替代的作用。依据《森林生态系统服务功能评估规范》(LY/T1721—2008),以济南市12个林分类型为研究对象,对济南市森林生态系统服务功能维持机制进行研究,得出济南市年森林生态系统涵养水源、保育土壤、固碳释氧、林木积累营养物质、净化大气环境、生物多样性保护的价值为251.80亿元。其中,涵养水源、固碳释氧、生物多样性保护排在前3位;不同林分类型生态系统服务功能价值量中黑杨类和柏类占绝对优势,而泡桐、落叶松和竹林生态系统服务功能较弱;不同林龄生态系统服务功能价值量以中幼龄林为主;济南市森林生态系统服务功能的维持机制,受到森林资源面积、林龄结构、森林起源以及自然保护区建设等诸多因素的影响。     

Long‐term outcomes of forest restoration in an urban park

Creating, restoring, and sustaining forests in urban areas are complicated by habitat fragmentation, invasive species, and degraded soils. Although there is some research on the outcomes of urban reforestation plantings during the first 5 years, there is little research on longer term outcomes. Here, we compare the successional trajectories of restored and unrestored forest sites 20 years after initiating restoration. The sites are located within the Rodman's Neck area of Pelham Bay Park, in the northeast corner of the Bronx in New York City (NYC), U.S.A. Compared with unrestored sites, we saw improvements in species diversity, greater forest structure complexity, and evidence of the regeneration and retention of native tree species in restored sites. In addition, we found differences in restoration outcomes depending on the level of intervention: clearing exotic shrubs and vines and planting native trees and shrubs improved tree diversity and canopy closure to a greater extent than clearing exotics alone, and the mechanical removal of invasive plants after the native plantings further improved some measures of restoration, such as tree species diversity and native tree regeneration. The results of this study suggest that the goal of a sustainable forest ecosystem dominated by native trees and other plant species may not be achievable without continued human intervention on site. In addition, these results indicate that the restoration approach adopted by NYC's reforestation practitioners is moving the site toward a more desirable vegetative community dominated by native species.     

海岛型旅游目的地生态补偿标准方法体系的构建与应用

海岛旅游可持续发展问题是学术界关注的焦点。但是,目前很少有涉及海岛旅游生态补偿方面的研究成果,这不利于对海岛旅游地的保护和恢复政策的制定。以生态补偿相关理论为基础,构建了一种由界定空间尺度、建立狭义生态补偿标准与广义生态补偿标准物质量核算体系、构建狭义生态补偿标准与广义生态补偿标准物质量评价模型和价值量评价模型、设计狭义生态补偿标准与广义生态补偿标准分摊方案等组成的海岛型旅游目的地生态补偿标准研究的方法体系;并进行了舟山市普陀区案例应用。结果表明:(1)2008年,舟山市普陀区旅游目的地的狭义生态补偿标准为687.2552×104元,广义生态补偿标准为6656.5528×104元;分摊次序Ⅱ阶段的生态补偿标准为687.2552×104元,分摊次序Ⅱ—Ⅲ阶段的生态补偿标准为5794.5577×104元,分摊次序Ⅱ—Ⅳ阶段的生态补偿标准为6656.5528×104元。(2)来自于舟山市、沪宁杭(除舟山市)、国内(除沪宁杭)和国际(含港澳台)的游客,分摊次序Ⅱ阶段均需实际承担1.90元/人次的生态补偿标准额度,分摊次序Ⅱ—Ⅲ阶段分别需实际承担1.90、3.94、29.96和207.57元/人次的生态补偿标准额度,分摊次序Ⅱ—Ⅳ阶段分别需实际承担3.29、5.33、31.35和208.96元/人次的生态补偿标准额度。     

Mitochondrial DNA synthesis in cell cycle mutants of saccharomyces cerevisiae

Mitochondrial DNA replication was examined in mutants for seven different Saccharomyces cerevisiae genes which are essential for nuclear DNA replication. In cdc8 and cdc21, mutants defective in continued replication during the S phase of the cell cycle, mitochondrial DNA replication ceases at the nonpermissive temperature. Replication is temperature sensitive even when these mutants are arrested in the G1 phase of the cell cycle with α factor, a condition where mitochondrial DNA replication continues for the equivalent of several generations at the permissive temperature. Therefore the cessation of replication results from a defect in mitochondrial replication per se, rather than from an indirect consequence of cells being blocked in a phase of the cell cycle where mitochondrial DNA is not normally synthesized. Since the temperature-sensitive mutations are recessive, the products of genes cdc8 and cdc21 must be required for both nuclear and mitochondrial DNA replication. In contrast to cdc8 and cdc21, mitochondrial DNA replication continues for a long time at the nonpermissive temperature in five other cell division cycle mutants in which nuclear DNA synthesis ceases within one cell cycle: cdc4, cdc7, and cdc28, which are defective in the initiation of nuclear DNA synthesis, and cdc14 and cdc23, which are defective in nuclear division. The products of these genes, therefore, are apparently not required for the initiation of mitochondrial DNA replication.