Chemical modification-mediated optimisation of bronchodilatory activity of mepenzolate,a muscarinic receptor antagonist with anti-inflammatory activity

The treatment for patients with chronic obstructive pulmonary disease (COPD) usually involves a combination of anti-inflammatory and bronchodilatory drugs. We recently found that mepenzolate bromide (1) and its derivative, 3-(2-hydroxy-2, 2-diphenylacetoxy)-1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octane bromide (5), have both anti-inflammatory and bronchodilatory activities. We chemically modified 5 with a view to obtain derivatives with both anti-inflammatory and longer-lasting bronchodilatory activities. Among the synthesized compounds, (R)-(–)-12 ((R)-3-(2-hydroxy-2,2-diphenylacetoxy)-1-(3-phenylpropyl)-1-azoniabicyclo[2.2.2]octane bromide) showed the highest affinity in vitro for the human muscarinic M3 receptor (hM₃R). Compared to 1 and 5, (R)-(–)-12 exhibited longer-lasting bronchodilatory activity and equivalent anti-inflammatory effect in mice. The long-term intratracheal administration of (R)-(–)-12 suppressed porcine pancreatic elastase-induced pulmonary emphysema in mice, whereas the same procedure with a long-acting muscarinic antagonist used clinically (tiotropium bromide) did not. These results suggest that (R)-(–)-12 might be therapeutically beneficial for use with COPD patients given the improved effects seen against both inflammatory pulmonary emphysema and airflow limitation in this animal model.     

The role of economic incentives and social norms in forest resource management

Forests are experiencing increasing pressure from human activities, which is leading to rapid deforestation and loss of ecosystem services. Although deforestation occurs for a wide range of reasons, one important reason is that landowners lack a long-term management view. I suggest that both economic incentives and social norms will work differently to reduce landowners’ motivation to deforest and to help landowners identify the long-term benefits that will be obtained by sacrificing short-term gain.     

The social brain?

The notion that there is a 'social brain' in humans specialized for social interactions has received considerable support from brain imaging and, to a lesser extent, from lesion studies. Specific roles for the various components of the social brain are beginning to emerge. For example, the amygdala attaches emotional value to faces, enabling us to recognize expressions such as fear and trustworthiness, while the posterior superior temporal sulcus predicts the end point of the complex trajectories created when agents act upon the world. It has proved more difficult to assign a role to medial prefrontal cortex, which is consistently activated when people think about mental states. I suggest that this region may have a special role in the second-order representations needed for communicative acts when we have to represent someone else's representation of our own mental state. These cognitive processes are not specifically social, since they can be applied in other domains. However, these cognitive processes have been driven to ever higher levels of sophistication by the complexities of social interaction.     

基于灾害视角的区域生态安全评价机理与方法——以辽河流域为例

随着人类活动对生态环境形成了巨大压力,频繁且类型众多的灾害构成对生态安全的现实或潜在的巨大威胁。目前人们主要针对确定性因素,基于"压力-状态-响应"(P-S-R)机理框架进行生态安全评价研究,评价结果反映区域总体的安全状态。但是在实际生产生活中人们关注的不仅是确定性因素的影响,还包括不确定性生态隐患因素的影响;不仅关注生态安全的现时状态,而且还关注生态安全未来的发展趋势。生态安全是动态性的,其演变过程、趋势和风险更重要。生态安全是地域性的,具体地域需要具体分析。针对生态安全特点和P-S-R框架研究的不足,研究结合地理科学和安全科学的基本理论,从灾害视角探讨了区域生态安全评价机理与方法:①根据评价对象各组成部分之间的相互关系与相互影响构建区域生态安全状态-隐患综合评价指标体系;②根据多目标决策乘法准则,提出状态-隐患耦合指数评价方法;③针对不同的安全影响要素空间递变特点以及数据的来源途径,探讨了"行政单元-动态格网"交互赋值技术;④以辽河流域为例,基于GIS网格技术进行了生态安全"可视化"空间差异评价。评价结果与实地考察基本一致,说明了这种研究方法具有一定的科学性,为制定区域生态化发展战略和规划提供了决策支持,也为建设生态安全预警系统奠定了基础。     

工业生态学研究现状与展望

工业生态学是一门新兴交叉学科,自诞生10多年来,其理论研究与实践活动已经取得了长足的进展。首先介绍了工业生态学的缘起,综述了目前国外工业生态学在原料与能量流动(工业代谢)、物质减量化、技术变革和环境、生命周期规划设计与评价、为环境设计、延伸生产者的责任、生态工业园(工业共生系统)、产品导向的环境策略、生态效益等主要领域的研究进展;分析了我国工业生态学的研究现状,并结合国际发展趋势提出了我国工业生态学未来的研究框架和主要研究领域     

线蚓科分类学研究进展

线蚓科隶属于环节动物门环带纲,迄今共记录32属650余种,是该纲的第二大科。它们广泛分布于土壤、海洋、淡水、河口和冰川等。其中,约2/3的线蚓科物种(近500种)为陆生种类,100余种仅分布在海洋中。尽管经历了200多年的探索,线蚓科仍然是认知最少的类群之一。尝试回顾人类对线蚓科环带动物分类学和系统发育学方面的认知历程和积累的知识体系,描述线蚓科关键的形态学分类特征以及线蚓科分类研究遇到的主要问题和障碍,展望了线蚓科分类学未来的研究方向。线蚓科的分类研究尚处于α分类阶段,体现在以物种探索为主和大量的已描述的物种需要验证等。而基于生物学物种概念(生殖隔离)的线蚓科物种探索,虽然有一些合理的逻辑解释,但缺乏严格的科学验证。线蚓科内多数属为复系,表明已建立的线蚓科分类系统仍然不能很好的反映线蚓科的自然进化历史。线蚓科分类面临的主要问题和障碍是未描述种类亟待发掘、已描述的物种需要验证、属/种的厘定以及现代属级概念的建立、DNA分类在线蚓科的应用和线蚓科内的系统发育关系研究亟待开展,以及物种探索的不平衡、经费和研究人才匮乏以及网络分类的缺失等。将分子学数据和系统发育物种概念纳入线蚓科的分类学研究,应该是线蚓科分类的一个方向。通过解读保守基因的信息,可以揭示线蚓科的祖先与它们生活的古环境长期斗争的历史,以及将优良的性状遗传给后代的过程和驱动力。而系统发育物种概念认为物种是拥有共同祖先的,物种仅能通过生殖隔离与系统发育重建一起加以验证。基于系统发育物种概念而构建的线蚓科分类系统,必将能真实的反映线蚓科内各分类单元的亲缘关系和进化轨迹。而将最新的线蚓科分类学知识传播于分类学知识的终端使用者,是线蚓分类学家的职责。这些知识将有助于提高人们对线蚓类在生态系统中功能的了解,如土壤有机质分解、养分矿化和健康评价以及评估气候变化等。     

Isolation of Taka-amylase A Peptides Required for Substrate Binding

An α-amylase from Aspergillus oryzae, Taka-amylase A (TAA), was cleaved into peptide fragments by an acid protease. Inactivation of TAA was greatly retarded by the addition of α-cyclodextrin or Ca²⁺. TAA peptide fragments were separated into two groups having no and high affinity to the substrate, soluble starch. This separation was done by the forced affinity chromatography method by a column of epichlorohydrin cross-linked soluble starch gel. Three peptides were isolated from the high-affinity fragments, purified by the ODS-120T column, and their amino acids were sequenced. Peptides I, II, and III originated from α2-helix, α3-helix, and β2-sheet, respectively, and all of these were located in the (β/α)₈ barrel of the main domain of TAA molecule. A stereo graphic view showed that Peptides I–III were at the cleft near the catalytic site. Occurrence of a Trp residue in all three peptides strongly suggested that Trp was very important in the binding of TAA to the substrate, soluble starch.     

Relationships between forced vital capacity and subjective responses to added resistive load to inspiration

1. 1. This study was conducted to investigate the effects of forced vital capacity on breathing pattern and subjective responses to inspiratory resistance.

2. 2. The subjects were divided into two groups according to their %FVC [large (L) and small (S) group; five subjects in each].

3. 3. Added inspiratory resistances were 0.6 (control), 1.5 (R1), 2.5 (R2), 3.1 (R3) cmH₂O · 1⁻¹ · s.

4. 4. Breathing pattern was analyzed by personal computer during rest and exercise with bicycle ergometer.

5. 5. The degree of sensation of breathing difficulty was expressed in SNS reported in our previous study.

6. 6. SNS in S group increased with resistance while no tendency was observed in L group. SNS in S group was significantly greater than that in L group at R3 condition.

7. 7. The breathing pattern of S group was characterized in smaller tidal volume and faster respiratory frequency compared to those of L group with no resistive load.

8. 8. However, outstanding changes in breathing pattern were observed in S group with longer inspiratory time and lower mean inspiratory flow rate when resistive loads were added, which led to increased tidal volume and decreased respiratory frequency.