Substrate protection of immobilized glucose isomerase

Using commercial immobilized glucose isomerase (SWETASE(R), Nagase Co.), the effect of substrate protection on enzyme deactivation has been studied in a batch manner. The data analysis was carried out based on Briggs-Haldane kinetics in which enzyme deactivation accompanying the protection of substrates was also considered. The protection factor was proposed to elucidate the dependence of the degree of substrate protection. The existence of the protection of glucose isomerase by the substrates has been verified experimentally. Also, the enzyme-substrate complex deactivates with a decay constant which is one-half that of the free enzyme. Theoretical analysis of enzyme deactivation with substrate protection offers an effective understanding which is essential for enzyme replacement and process optimization.     

Protecting vernal pools: a model from Massachusetts,USA

Ephemeral ponded wetlands, often referred to as vernal pools in the wetland’s lexicon of the northeastern United States, are in need of protection from outright loss, catastrophic alteration, and disruption of natural processes in the surrounding landscape, because of their great importance to a characteristic wildlife fauna. The state of Massachusetts, USA provides a useful model for vernal pool protection. Vernal pools have been specifically protected under state wetlands regulations since 1987 and many of the state’s municipalities have added additional, more stringent protection under local wetland bylaws. Some vernal pools are also protected under federal wetlands protection law. The protection of vernal pools in Massachusetts is based on a certification process in which biological data are collected to demonstrate that a wetland provides vernal pool functions. Once certified, and if a pool meets jurisdictional requirements, regulatory restrictions are placed on development and other activities proposed within the pool. The regulatory protection for vernal pools in Massachusetts has resulted in the prevention of outright loss and degradation of many vernal pools across the state. However, a 2001 US Supreme Court decision, referred to as the SWANCC decision, may result in a loss of federal jurisdiction over many vernal pools, protection that is especially valuable for pools that do not meet state regulatory criteria. Of significant importance is a lack of protection in existing regulations of the upland non-breeding habitat surrounding vernal pools, which has been shown to be of critical importance to the animals that rely on the pools. Despite the shortcomings of the regulatory protection model in Massachusetts, it has been especially effective as a catalyst for environmental and wildlife awareness, public participation in the wetlands regulatory process, and as an extremely valuable tool in environmental education and outreach.     

艰难梭菌荚膜致病作用的初步研究

本文在我室先前研究的基础上,以3株艰难梭菌的荚膜多糖提取物、全菌悬液以及全菌免疫血清分别在小鼠中进行半数致死量和保护试验等动物实验,以探讨艰难梭菌荚膜的致病作用。结果测得其中一株艰难梭菌的荚膜多糖对小鼠有致死毒性,其LD50为2.83mg,特异性抗血清保护试验证实艰难梭菌免疫血清对动物有保护作用。实验结果可能为进一步研究艰难梭菌荚膜的致病作用提供了参考资料。     

The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors

Even before the partial success of a preventive HIV vaccine in a recent Phase III clinical trial, there had been an active research effort to determine one or more immune correlates of protection for HIV infection. This effort has been hampered by the lack of natural protective immunity against HIV. As a result, most of the studies have focused on long-term non-progressive infection or other clinical situations, none of which fully recapitulates protective immunity against HIV. Although this effort has been successful in defining characteristics of T cells in acute and non-progressive HIV infection, and has therefore greatly expanded our knowledge of the immunopathogenesis of AIDS, its success in defining immune correlates of protection is less clear. In this Opinion article we offer a perspective on how successful this effort has been in defining immune correlates of protection that have been, or will be, of use in the development of an HIV vaccine. Our view is that investing in an iterative approach to human vaccine efficacy trials of sufficient size and sampling frequency will improve the likelihood that an immune correlate of vaccine protection will be defined.     

Microscopic stability of cold shock protein A examined by NMR native state hydrogen exchange as a function of urea and trimethylamine N-oxide

Native state hydrogen exchange of cold shock protein A (CspA) has been characterized as a function of the denaturant urea and of the stabilizing agent trimethylamine N-oxide (TMAO). The structure of CspA has five strands of beta-sheet. Strands beta1-beta4 have strongly protected amide protons that, based on experiments as a function of urea, exchange through a simple all-or-none global unfolding mechanism. By contrast, the protection of amide protons from strand beta5 is too weak to measure in water. Strand beta5 is hydrogen bonded to strands beta3 and beta4, both of which afford strong protection from solvent exchange. Gaussian network model (GNM) simulations, which assume that the degree of protection depends on tertiary contact density in the native structure, accurately predict the strong protection observed in strands beta1-beta4 but fail to account for the weak protection in strand beta5. The most conspicuous feature of strand beta5 is its low sequence hydrophobicity. In the presence of TMAO, there is an increase in the protection of strands beta1-beta4, and protection extends to amide protons in more hydrophilic segments of the protein, including strand beta5 and the loops connecting the beta-strands. TMAO stabilizes proteins by raising the free energy of the denatured state, due to highly unfavorable interactions between TMAO and the exposed peptide backbone. As such, the stabilizing effects of TMAO are expected to be relatively independent of sequence hydrophobicity. The present results suggest that the magnitude of solvent exchange protection depends more on solvent accessibility in the ensemble of exchange susceptible conformations than on the strength of hydrogen-bonding interactions in the native structure.     

Benzophenone semicarbazone protection strategy for synthesis of aza-glycine containing aza-peptides

Aza-glycine has been incorporated into peptide mimics as a tool for studying the active conformation and characterizing structure-function relationships for activity. Side reactions, such as intramolecular cyclizations to form hydantoins and oxadiazalones, have, however, inhibited efforts to make activated aza-Gly residues in solution using carbamate protection. Herein, we describe efficient incorporation of aza-glycine into aza-peptides using diphenyl hydrazone protection. Hydrazone acylation with p-nitrobenzyl chloroformate provided the protected aza-Gly activated ester, which was used to acylate a set of amino ester and amino acids to provide aza-Gly-Xaa aza-dipeptide fragments for peptide synthesis. Removal of the hydrazone protection was performed under acidic conditions to provide the hydrochloride salt of the aza-Gly residue for subsequent elongation of the aza-peptide chain using standard coupling conditions. A proof of concept for the use of benzophenone protection has been established by the synthesis of an aza-peptide analog of a potent activator of caspase 9 in cancer cells.     

Wolbachia-mediated antibacterial protection and immune gene regulation in Drosophila

The outcome of microbial infection of insects is dependent not only on interactions between the host and pathogen, but also on the interactions between microbes that co-infect the host. Recently the maternally inherited endosymbiotic bacteria Wolbachia has been shown to protect insects from a range of microbial and eukaryotic pathogens. Mosquitoes experimentally infected with Wolbachia have upregulated immune responses and are protected from a number of pathogens including viruses, bacteria, Plasmodium and filarial nematodes. It has been hypothesised that immune upregulation underpins Wolbachia-mediated protection. Drosophila is a strong model for understanding host-Wolbachia-pathogen interactions. Wolbachia-mediated antiviral protection in Drosophila has been demonstrated for a number of different Wolbachia strains. In this study we investigate whether Wolbachia-infected flies are also protected against pathogenic bacteria. Drosophila simulans lines infected with five different Wolbachia strains were challenged with the pathogenic bacteria Pseudomonas aeruginosa PA01, Serratia marcescens and Erwinia carotovora and mortality compared to paired lines without Wolbachia. No difference in mortality was observed in the flies with or without Wolbachia. Similarly no antibacterial protection was observed for D. melanogaster infected with Wolbachia. Interestingly, D. melanogaster Oregon RC flies which are naturally infected with Wolbachia showed no upregulation of the antibacterial immune genes TepIV, Defensin, Diptericin B, PGRP-SD, Cecropin A1 and Attacin D compared to paired flies without Wolbachia. Taken together these results indicate that Wolbachia-mediated antibacterial protection is not ubiquitous in insects and furthermore that the mechanisms of antibacterial and antiviral protection are independent. We suggest that the immune priming and antibacterial protection observed in Wolbachia-infected mosquitoes may be a consequence of the recent artificial introduction of the symbiont into insects that normally do not carry Wolbachia and that antibacterial protection is unlikely to be found in insects carrying long-term Wolbachia infections.     

Ischemic preconditioning: from the first to the second window of protection.

In many species one or more brief coronary occlusions limit the injuries which a subsequent ischemia-reperfusion can produce in the myocardium. A similar protection has been observed in the majority of organ systems. A first period or window of protection can lasts up to 3 hours and is followed by a second window of protection (SWOP) which begins about 24 hours after the brief coronary occlusions and lasts about 72 hours. Increase of the release of endogenous agents such as adenosine and nitric oxide (NO) may be responsible for both windows through the activation of a protein-kinase C (PKC) which in turn activates ATP sensitive potassium (K+(ATP)) channels. Nitric oxide is also reported to act directly on K+(ATP) channels. Recently, it has been suggested that the channels involved in the protection are mitochondrial rather than sarcolemmal. In SWOP the origin of NO is attributed to the activity of an inducible NO-synthase. Free oxygen radicals released during preconditioning are likely to take part in the delayed protection through the production of peroxynitrite which activates PKC and through the increase of the activity of antioxidant enzymes such as Mn superoxide-dismutase. The production of heat shock proteins is considered a marker rather than a mechanism of SWOP.     

Haemoglobinopathies and resistance to malaria

The haemoglobinopathies have a celebrated role in the study of human genetics as the first examples of balanced polymorphisms described in human populations. Over the last 50 years, considerable evidence has been provided to show that these traits do confer protection from malaria. More recently, the underlying mechanisms of protection have been examined. This short review summarizes these studies and where possible shows how the putative mechanisms of protection may be linked to redox processes.     

区域生态经济型防护林体系建设模式智能决策支持系统的研制开发

根据生态经济型防护林体系及其建设模式的内涵,研制开发出了以专家为核心,包括数据及数据库、图形及图形库、模型及模型库等模块的智能决策支持系统,以便为给定区域提供有关生态经济型防护林体系建设方面的决策服务。     

基于生境质量和生态安全格局的阿勒泰地区生态保护关键区域识别

随着生态文明建设上升为国家战略,生态安全与保护修复格局的识别成为国土空间规划战略中关于生态空间保护的重要内容。为了促进区域生态系统的保护修复及有效管理,从空间尺度上对区域生态安全和修复区域的识别必不可少。利用InVEST模型的Habitat Quality模块分析了阿勒泰地区1995年、2005年和2018年的生境质量变化状况,从生态环境保护的角度出发构建区域生态安全格局,结果发现：（1）1995-2018年阿勒泰地区生境质量处于中等水平,总体呈下降趋势,说明当地生态系统有不断退化趋势;（2）以生态结构系统性和生态过程完整性为目标,通过MSPA分析结合景观连通性识别出15块生态源地,处于阿勒泰北部的山间林地和乌伦古湖区域;利用ArcGIS软件的Cost Distance工具识别出阿勒泰地区有效生态廊道38条,长约2466km,总面积约80.08km²,其中草地和林地是生态廊道穿越的重点区域;识别出最小阻力路径与生态廊道交叉处的生态节点52个,主要分布在草地和林地区域;（3）通过生境质量与最小累积阻力值识别出三类生态保护关键区域,分别为生态涵养区、生态维护区和生态保育区,结合各类生态保护关键区域的存在的生态问题提出不同的生态保护方向。研究结果为阿勒泰地区生态保护修复按照三类生态保护分区分别提出了不同的保护方向,可为阿勒泰地区国土空间生态保护修复关键区域识别和为保障区域生态系统整体保护及可持续发展政策制定提供参考。     

文化线路视野下的米仓道（巴中段）遗产认知框架分析

在中国文物保护体系下,古道等遗产线路类的文物保护工作尚未能完全对接国际文化线路的保护理念,文化线路的国内文物保护体系和国际保护视野面临无法衔接的困境。以国际文化线路“物质线路”和“衍生要素”的分析视野,将具有申遗背景同时需要对接文物保护工作的米仓道（巴中段）作为对象,通过梳理其时空范畴和价值认知,分别辨析作为国内文物保护体系的交通遗产构成框架,以及对接申遗工作的文化线路衍生遗产要素。基于此,遗产线路衔接国内文物保护体系和“文化线路”申遗保护要求的工作框架得以厘清,可为国内面临类似研究需求的文化线路类遗产提供借鉴。     

跨国公司生物技术知识产权保护策略分析——以棉花转化体MON531为例

近年来,转基因棉花种植面积在多个国家得到了快速增长。为深入研究转基因抗虫棉花的技术体系和知识产权保护状况,现以棉花转化体MON531为例研究跨国生物公司的知识产权保护策略。结果显示,目前MON531转化体涉及3件处于有效保护期限内的专利,并在多个国家受到保护,实现了从功能基因及调控元件到最终商业化品种的全方位有效保护。申请人还通过申请植物品种权对下游的品种进行保护,美国有19件品种获得授权,在中国仅有1件相关申请处于审查中。对棉花转化体MON531技术体系的知识产权保护策略的研究,可以为我国研发转基因作物并采取知识产权保护提供有利的借鉴。     

基于生态系统服务的山水林田湖草生态保护修复研究——以南太行地区鹤山区为例

开展山水林田湖草生态保护修复是生态文明建设的重要内容,将生态系统服务评价成果与山水林田湖草生态保护修复工程相结合,以国家第三批山水林田湖草生态保护修复试点-河南省南太行地区鹤山区为例,探究生态系统服务评价成果在区域山水林田湖草生态保护修复中的应用。结果表明,近年来鹤山区生态系统服务价值整体呈下降趋势且生态环境破坏严重。其中,2014-2017年鹤山区各土地类型二级服务ESV减少了303.95万元。研究期内,水资源供给、气体调节功能、气候调节、净化环境、水文调节、土壤保持、生物多样性和美学景观等8项生态服务价值都出现不同程度的下降;在鹤山区生态保护修复工作中需要重点关注生态系统的水文调节、净化环境、土壤保持和生物多样性等服务功能,相应的生态保护修复工程应集中在河道生态修复与湿地保护、矿山生态环境修复与土地整治、森林及生物多样性保护修复;鹤山区山水林田湖草生态保护修复工程能够提升区域生态服务价值。其中,工程实施后的生态系统服务价值总量预计能达到36407.95万元,比2017年增加7741.96万元,增长率为27%且各项生态服务价值均有提升。研究结果对鹤山区山水林田湖草生态保护修复工程的实施有一定的指导性作用。     

Trypanosoma gambiense and T. equiperdum: characterization of variant specific antigens

It has been shown that by a simple procedure the variant specific protective antigen can be isolated from both T. gambiense and T. equiperdum. The protection afforded mice by this antigen is relatively long term and a high percentage of mice has complete protection. It has been suggested that the antigens are highly antigenic and although antigenically unique for each relapse strain, they have one or more common physical characteristic. It is therefore hypothesized that a multivalent vaccine might be prepared by similar procedures for protection against trypanosomiasis.     

Assessment of coastal protection as an ecosystem service in Europe

Mapping and assessment of ecosystem services is essential to provide scientific support to global and EU biodiversity policy. Coastal protection has been mostly analysed in the frame of coastal vulnerability studies or in local, habitat-specific assessments. This paper provides a conceptual and methodological approach to assess coastal protection as an ecosystem service at different spatial–temporal scales, and applies it to the entire EU coastal zone. The assessment of coastal protection incorporates 14 biophysical and socio-economic variables from both terrestrial and marine datasets. Those variables define three indicators: coastal protection capacity, coastal exposure and human demand for protection. A questionnaire filled by coastal researchers helped assign ranks to categorical parameters and weights to the individual variables. The three indicators are then framed into the ecosystem services cascade model to estimate how coastal ecosystems provide protection, in particular describing the service function, flow and benefit. The results are comparative and aim to support integrated land and marine spatial planning. The main drivers of change for the provision of coastal protection come from the widespread anthropogenic pressures in the European coastal zone, for which a short quantitative analysis is provided.     

免疫抑制剂治疗对儿童疫苗诱导的免疫保护性的影响及其相关机制

疫苗是目前公认的预防传染病的有效手段,接种疫苗可极大降低人群传染病的发病率和病死率。随着现代医学的进展,接受免疫抑制剂治疗肿瘤、器官移植、造血干细胞移植及慢性病的患儿生存率有了很大提高,但免疫抑制剂的使用会影响疫苗诱导的免疫保护效果及儿童时期疫苗接种的安全性,使这部分免疫低下的特殊儿童成为疫苗可预防疾病的高危易感人群。本文综述了免疫抑制剂对儿童疫苗免疫保护性的影响及其相关机制。     

青藏高原山水林田湖草生态保护修复模式——以拉萨河流域为例

山水林田湖草生态保护与修复是推进生态文明建设的必然要求。青藏高原是我国生态屏障区、水源涵养区和生态脆弱区,生态地位独特、生态保护责任重大。为此,中央及地方政府高度重视青藏高原生态文明建设,积极开展山水林田湖草生态保护修复试点工程。从青藏高原山水林田湖草生态保护与修复试点的特殊性出发,以拉萨河流域为例梳理了其主要的生态保护修复工程项目,提炼了青藏高原山水林田湖草生态保护与修复的技术路线,从参与主体、整合要素、运行保障、实施目标等方面总结了青藏高原多部门跨区、多要素综合、多渠道协作、多目标耦合的山水林田湖草联动治理模式,从山、水、林、田、湖、草六大生态要素出发归纳了青藏高原生态保护修复的分类指导-精准施策的实践框架,以期对青藏高原山水林田湖草生态建设情况有一个清晰的认识,并为全国其他地区系统开展山水林田湖草生态保护修复工作提供借鉴。     

Haemoglobinopathies and resistance to malaria

Abstract

The haemoglobinopathies have a celebrated role in the study of human genetics as the first examples of balanced polymorphisms described in human populations. Over the last 50 years, considerable evidence has been provided to show that these traits do confer protection from malaria. More recently, the underlying mechanisms of protection have been examined. This short review summarizes these studies and where possible shows how the putative mechanisms of protection may be linked to redox processes.     

心肌内源性保护研究中的若干问题与展望

自上世纪80年代中期Murry及Currie等分别发现缺血预适应（ischemic preconditioning,IPC）与热休克反应（heat shock response,HSR）具有明显的心肌保护作用以来,有关心肌内源性保护作用的研究引起了学术界的广泛关注。经过20多年的大量研究,心肌内源性保护研究已在多方面取得了进展,积累了丰富的研究经验,建立了基本的理论框架,其中以IPC和热休克蛋白（heat shock proteins,HSPs）的研究最为引人注目。但基于问题本身的复杂性,目前在心肌内源性保护机制研究中还存在许多待解决的问题。本文拟就IPC、HSPs、心肌内源性保护研究模型与研究策略等问题进行阐述,并对上述领域未来的研究方向进行分析和展望。