重组M2e-鞭毛蛋白流感疫苗在健康成人中的安全与免疫原性

<正>背景:基质蛋白2的胞外域(M2e)是一种有希望的具有广谱保护作用的A型流感疫苗候选制剂,因为它是高度保守的,而且抗M2e抗体在动物模型中具有保护作用。STF2.4x M2e(VAX102)是一种重组融合蛋白,即M2e抗原的4个串联拷贝与鼠伤寒沙门菌的鞭毛蛋白相连接而构成的重组融合蛋     

迁地保护应当具有明确的灵活性

早期的新闻报道中提到国家植物园体系“逐步实现中国85%以上野生本土植物、全部重点保护野生植物种类得到迁地保护”的建设目标引发了质疑。实际上,《中国植物园体系布局方案》明确了更为实际的目标,包括到2025年设立5个左右国家植物园,实现70%以上的国家重点保护野生植物得到迁地保护;到2035年设立10个左右国家植物园,实现80%以上的国家重点保护野生植物得到有效迁地保护。植物园体系应当建立明确的迁地保护分级标准,即使在迁地栽培无法达到最高级别的保护标准时,仍可视为某种较低级别的迁地保护。迁地保护工作应与中国植物园体系有机结合,包括国家植物园、地区优秀植物园和地方植物园。通过全国植物引种数据联网共享的可能性,区域性和基层植物园可参与到迁地保护工作中,共同承担任务份额。迁地保护与就地保护、引种驯化并非对立的关系。就地保护优于迁地保护,但二者是相辅相成的关系。迁地保护和引种驯化并非绝对对立,可实现既保护又开发的目标。总体而言,未来迁地保护工作的一个重要方向是建立清晰的分级标准和数据网络,以明确迁地保护与其他保护形式的关系,实现明确的灵活性。     

关于植物迁地保护若干问题的讨论

植物迁地保护将是正在建设的国家植物园体系的核心任务,然而,有关植物迁地保护在植物多样性保护中的地位与作用、我国植物迁地保护的目标应该如何确立等诸多问题尚待讨论。本文通过文献研究,简要回顾了植物迁地保护的发展历史、过去40年国内外植物迁地保护取得的成绩,澄清了人们对植物迁地保护工作的一些疑虑;结合《昆明-蒙特利尔全球生物多样性框架》和即将发布的《支持<昆明-蒙特利尔全球生物多样性框架>实施的植物保护相关的自愿补充行动》,提出我国植物迁地保护的目标应该为“对所有受威胁植物实施有效的迁地保护,包括保护其遗传的多样性和代表性”。     

国家尺度自然保护地生态系统联网监测指标体系构建与应用研究

自然保护地是维护国家生态安全, 提升生物多样性保护成效的重要载体, 对保护地生态系统进行实时、高频、多尺度的监测是认知其动态变化的有效手段, 也是实现自然保护地生态系统健康管理的基石。由于目前我国没有形成自然保护地生态系统监测网络, 缺少统一的联网监测指标体系, 导致多数自然保护地生态系统组成家底不清、动态不明, 应对生物多样性保护新问题的能力不足, 并且在国家尺度上的自然保护地生态系统健康状况及保护成效评估缺乏联网监测数据支撑。因此, 亟需构建国家尺度的自然保护地生态系统组成和动态监测网络, 以及一套科学、系统、规范的自然保护地生态系统联网监测指标体系。该文针对自然保护地生物多样性和生态系统监测的目标和内容, 参考国内外现有的生态系统监测网络的指标体系, 确定了自然保护地生态系统联网监测指标体系建立和选取的基本原则, 建立了一套适用于国家尺度的自然保护地生态系统联网监测指标体系, 并在6个国家级自然保护区进行示范。构建的指标体系针对构成生态系统的6类关键要素(生境要素、生物要素、气象要素、土壤要素、大气和水环境要素、景观要素)制定了30个监测指标, 有效应用于森林、草地、荒漠、湿地等生态系统类型的自然保护地, 能够实现对不同类型自然保护地生态系统组分和结构的现状和演变特征进行长期、动态化监测, 并可为自然保护地保护成效评估和健康管理提供规范化、标准化的基础数据。     

基于爱知生物多样性目标11的我国自然保护地管理有效性评估进展与分析

本文基于我国相关政府部门、国际机构、科研机构和文献关于我国自然保护地管理有效性评估数据, 梳理和分析了我国针对爱知生物多样性目标11的自然保护地管理有效性评估的进展情况。结果显示, 我国已按时完成了爱知生物多样性目标11中2015年之前对60%以上自然保护地管理有效性评估的指标; 目前已开展管理有效性评估的自然保护地面积达136.19万km², 占我国自然保护地面积(186.60万km²)的72.99%; 我国自然保护地管理有效性受多方关注。本研究调查数据与世界自然保护地数据库、自然保护地管理有效性全球数据库的数据差异较大; 我国自然保护地管理有效性评估工具多样, 各类型自然保护地管理有效性评估工作进展差异显著, 管理有效性评估标准化和连续性有待提高。最后, 提出了如下建议: 加强自然保护地整体性和连通性; 参考世界自然保护区委员会的评估框架和世界自然保护联盟自然保护地绿色名录标准, 按照国家公园、自然保护区和自然公园分类制定管理有效性评估规范并将评估制度化; 有效利用评估结果促进我国自然保护地建设的标准化、科学化并建立激励机制等。     

试论植物园功能变迁与中国国家植物园体系建设

植物资源是自然生态系统的基本组成部分, 是经济社会可持续发展的重要物质来源, 植物多样性是关系到国家生态安全和生物安全的战略资源。就地保护和迁地保护是植物多样性保护的两种主要方法, 构建以国家公园为主体的自然保护地体系是就地保护的主要形式, 构建以国家植物园为引领的植物园体系是迁地保护的主要形式, 二者相辅相成, 共同形成我国较为完整的植物多样性保护体系。通过建设国家植物园体系对我国植物多样性进行迁地保护, 同时开展科学研究、园林展示、科普教育和资源开发利用, 对深入推进生态文明建设和高质量发展具有重要意义。本文回顾了植物园的功能变迁、全球和中国植物园分布与数量以及植物迁地保护现状,讨论了植物园与植物迁地保护的关系, 在此基础上, 提出了我国国家植物园的定义及设立标准, 进而讨论了建设国家植物园体系的意义、挑战、统筹迁地保护和就地保护等问题, 最后提出了我国国家植物园体系的建设目标、管理体制、空间布局和认证等方面的建议, 以期为我国的国家植物园体系建设提供参考。     

自然保护地保护成效评估: 进展与展望

自然保护地(protected areas)保护成效是指自然保护地对主要保护对象的保护效果, 及其在维持生物多样性和保障生态系统服务功能等方面的综合成效。近年来自然保护地保护成效评估逐渐成为国内外的研究热点之一。 本文分别从不同空间尺度、评估对象、评估方法以及评估指标等方面综述了相关的研究进展。总体来看, 近年来的研究已基本覆盖了全球、区域、国家和单个自然保护地等不同尺度, 针对森林、湿地、草地和荒漠等代表性生态系统以及野生动植物等主要保护对象进行了评估, 发展了“matching”技术等更为有效的分析方法, 探索了系统的自然保护地保护成效评估指标体系, 并应用一些指标进行了保护成效的案例研究。自然保护区(nature reserve)是我国自然保护地的主体, 近年来我国自然保护区相关管理部门也相继开展了保护成效评估工作, 建议未来进一步加强自然保护区网络尺度和各类型自然保护区的保护成效评估研究, 将自然保护区保护成效评估与管理评估相结合, 研究自然保护区保护成效面临的新问题和潜在影响, 为提升我国自然保护区管理质量提供科学依据。     

自然保护地生物多样性保护研究进展

建立自然保护地是保护生物多样性最为重要的措施之一。总体来看, 自然保护地生物多样性保护研究主要围绕关键生态系统以及珍稀濒危物种等保护对象的状态以及变化两个层面进行, 并重点关注自然保护地数量与面积、保护了多少重要生态系统和物种、能否有效保护生物多样性等一系列科学问题。然而, 在自然保护地生物多样性保护研究方面, 还缺少针对上述研究领域的系统性综述。为此, 本文系统梳理了自然保护地空间布局及其与生物多样性分布的关系、自然保护地生物多样性变化及其保护成效等近20年来相关领域的研究进展。自然保护地的空间布局以及与生物多样性分布的关系主要围绕自然保护地与生物多样性在某一阶段的状态开展研究, 致力于探究自然保护地“保护多少” “代表性如何” “在哪儿保护”等一系列关键科学问题。同时, 自然保护地内的生物多样性会随着气候变化、人类活动以及自身演替等发生时空动态变化, 基于自然保护地生物多样性变化分析, 各国学者在全球尺度、国家尺度和单个自然保护地进行了大量的保护成效评估研究, 并逐渐发展出了自然保护地内外配对分析方法以提升保护成效评估的精度, 进而识别出不同自然保护地的主要影响因素。在此基础上, 本文进一步对自然保护地生物多样性保护研究提出了展望, 主要包括: (1)综合考虑自然保护地生物多样性状态和变化; (2)开展多目标协同的自然保护地空间优化布局; (3)强化自然保护地主要保护对象的识别、调查与监测; (4)提升自然保护地的质量和连通性; (5)探究自然保护地管理措施与保护成效的关联机制。本文可为“2020年后全球生物多样性框架”的制定与实施特别是在自然保护地体系建设与优化方面提供参考与借鉴。     

中国自然保护地整合优化关键问题

自然保护地建设是国际公认的保护生物多样性、提供优质生态产品与服务、维系生态系统健康的最重要和最有效途径。自然保护地作为中国自然生态空间最精华和最重要的组成部分,是建设生态文明的核心载体,是美丽中国的重要象征,在维护国家生态安全中具有首要地位(唐小平等, 2019)。从1956年建立第一个自然保护地以来,中国自然保护地建设取得了巨大成就,保护体系逐步完善,建立了由自然保护区、风景名胜区、森林公园、地质公园、湿地公园等组成的数量众多、类型丰富、功能多样的自然保护地体系。截止到2019年底,中国已有各类自然保护地约1.18万处,大约覆盖了陆域国土面积的18%,占海域面积的4.6%(高吉喜等,2019),无论从数量上还是面积上均位居世界前列,为保护生物多样性、自然景观及自然遗迹,维护国家和区域生态安全等发挥了重要作用。     

森林遗传资源保护研究进展

森林遗传资源的保护事关现代及后代的利益,已引起全球的极大关注,自70年代以来,就地保护与迁地保护作为主要的战略在森林遗传资源保护实践中使用。一般来说森林遗传资源的就地保护可以通过建立自然保护区来实现。迁地保护主要包括种子库、田间基因库、种子园及细胞或组织培养等技术。就地保护和迁地保护应当相互补充,两者结合使用是保存森林遗传多样性的有效方法。对森林遗传资源保护战略的选择以及因贸易而濒危的热带材用树及其保护问题也作了简要评述。     

Synthesis and photolytic cleavage of bovine insulin B22-30 on a nitrobenzoylglycyl-poly (ethylene glycol) support

The synthesis of the C-terminal nonapeptide of bovine insulin B-chain is described. 4-(Bromomethyl)-3-nitrobenzoylglycyl-poly(ethylene glycol) Mr = 15,000) was used as soluble support. The C-terminal alanine was first converted to Boc-Ala-O-(2-nitro-4-carboxy) benzyl ester which was then coupled to Gly-PEG via DCC activation. The synthesis was performed using the in situ symmetrical anhydride coupling method. Cleavage of the protected peptide from the polymeric support was achieved by photolysis. The product was then chromatographed on a column of Sephadex LH-20. All the protecting groups of a sample were removed with liquid HF and the unprotected crude peptide was purified by ion-exchange chromatography on CM-Sephadex to obtain an electrophoretically and chromatographically pure peptide. The identity of this peptide was confirmed by field desorption mass spectrometry and amino acid analysis. Circular dichroism measurement suggests that the free nonapeptide possesses a disordered conformation. The nonapeptide was tested for the racemization of the individual amino acids by gas chromatography and the results showed that no residue was significantly racemized.     

Suppression of steroidogenesis in mice granulosa cells by a synthetic nonapeptide fragment of human seminal plasma inhibin.

A synthetic nonapeptide, which is C-terminal sequence of 94-amino acid of prostatic inhibin peptide was tested for progesterone and estrogen secretion by mouse granulosa cell cultures. Nonapeptide suppressed the progesterone and estrogen synthesis, the magnitude of suppression was highest at 5 ng dose level for progesterone and 50 ng dose level for estradiol. The study suggests that, nonapeptide exerts its effect by impairing the binding of FSH to granulosa cell receptors.     

Large-scale synthesis of hematoregulatory nonapeptide SK&F 107647 by fragment coupling.

Linear and convergent routes for the large-scale preparation of the hematoregulatory nonapeptide (Glp-Glu-Asp)2-DAS-(Lys)2 (2, SK&F 107647) were investigated. A convergent approach ('3 + 2'-route employing Boc-and benzyl ester protecting groups) was selected for the preparation of multihundred-gram quantities of 2. Key steps were the preparation and the coupling of tripeptide hydrochloride (HCl.H)2-DAS-(Lys(Z)-OBn)2 (6, DAS-2,7-L,L-diaminosuberic acid) and tripeptide Glp-Glu(OBn)-Asp(OBn)-OH (26). Several coupling reagents were investigated in order to reduce the amount of epimerization of this fragment coupling. TDBTU [O-(3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-yl-1,1,3,3-tetrameth yluronium tetrafluoroborate] was identified as the condensation reagent of choice. Using this synthetic route > 97% pure final product in an overall yield of 35% calculated on di-Boc protected 2,7-L,L-diaminosuberic acid was prepared.     

Synthesis and characterization of the hexenuronic acid model methyl 4-deoxy-beta-L-threo-hex-4-enopyranosiduronic acid

A facile synthetic scheme for the preparation of methyl 4-deoxy-β-l-threo-hex-4-enopyranosiduronic acid utilizing the commercially available methyl α-d-galactopyranoside as starting material has been developed. The synthesis sequence comprises six high yielding reaction steps: TEMPO oxidation, acetylation, methanolysis of the lactone, acetylation, β-elimination, and final removal of the protecting groups. Only one column chromatographic purification is needed throughout the whole sequence. The overall yield is 60%. The final product has been characterized by NMR, Raman, UVRR, FTIR, and HRMS.     

Enzymatic purification of chemically synthesized oligodeoxyribonucleotides prior to removal from a solid-support

A novel combined solid-phase DNA synthesis and solid-phase DNA purification strategy is described. Removal of all N-, cap-, and phosphate protecting groups while maintaining a 5'-blocking group on the final product followed by a 5'- specific exonuclease digestion of failure sequences with the synthetic DNA still attached to the solid phase yields an essentially pure oligomer.     

High-performance liquid chromatographic assay for farnesyl-protein transferase activity with dabsylated peptide

An HPLC assay for farnesyl-protein transferase activity using a dabsylated peptide is described. The substrates used were a synthetic dabsylated nonapeptide, N-dabsyl-l-serinyl-l-methioninyl-l-glycinyl-l-leucinyl-l-prolinyl-l-cysteinyl-l-valinyl-l-valinyl-l-methionine, corresponding to the C-terminal peptide seqeunce of human N-Ras p21 without the N-terminal serine, and farnesyl disphosphate. The product was separated from the substrates on a reversed-phase C₁₈ column, using gradient elution with acetonitrile (0.05% trifluoroacetic acid)-water (0.1% trifluoroacetic acid) and was detected at 436 nm. The addition of the farnesyl group to the peptide was confirmed by MS and NMR. Enzymatic reaction was ascertained from the dependences on time, on the protein of the enzyme source and on the substrates. The reaction was specifically inhibited by l-cysteinyl-l-valinyl-l-valinyl-l-methionine, the tetrapeptide corresponding to the “CAAX” motif. The limit of detection was 2 pmol per 100-μl reaction mixture. The farnesyl-protein transferase activity can quantitatively be measured up to 200 μg cytosolic protein in human liver. This method provides a convenient and quantitative assay for crude materials, such as tissue homogenate from clinical samples, without the use of radioactive probes and large amounts of Ras protein.     

The constitution and properties of phosphorylated and unphosphorylated C-terminal fragments of progastrin from dog and ferret antrum

Antibodies to the extreme C-terminal tryptic (nona-) peptide fragment of porcine progastrin have been used in radioimmunoassay to identify progastrin fragments in dog, ferret and pig antral mucosa extracts and to monitor their purification. In addition to previously characterised phosphorylated and unphosphorylated C-terminal tryptic peptides of porcine progastrin a minor form corresponding to the C-terminal octapeptide (i.e. des-Ser C-terminal nonapeptide) was isolated and characterised. The latter form together with phosphorylated and unphosphorylated forms of the nonapeptides were also isolated and chemically characterised from dog antrum, and the unphosphorylated nonapeptide was characterised from ferret antrum. The primary amino acid sequences of the dog, ferret and pig nonapeptides were identical. In ferret the unphosphorylated nonapeptide predominated, and in dog the phosphorylated form predominated; in pig both forms of the nonapeptide were well represented. Intact progastrin was identified in gel filtration eluates of extracts of all 3 species, but occurred only in relatively low concentrations. The nonapeptides did not stimulate acid secretion in the conscious gastric fistula rat and they did not modify the acid response to G17. Phosphorylation of progastrin-derived peptides is evidently well conserved across a range of species even though there appear to be differences in the relative proportions of phosphorylated and unphosphorylated forms.     

Synthesis of analogs of the serum thymic nonapeptide, "facteur thymique serique" (FTS). Part I.

Analogs of FTS (Facteur Thymique Sérique), less than :formula: (see text), a circulating thymic factor, were prepared by replacing the amino acid residues in positions 1, 2, 8 and 9, or by shortening the nonapeptide chain at the N- or C-terminal end. These peptides were synthesized by two different schemes using the conventional synthesis in solution.     

Solution synthesis of human midkine,a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five disulphide bonds

Human midkine (hMK), a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five intramolecular disulphide bonds, was synthesized by solution procedure in order to demonstrate the usefulness of our newly developed solvent system, a mixture of dichloromethane or chloroform and trifluoroethanol. The final protected 121-residue peptide was assembled from two large fully protected intermediates, Boc-(1–5 9)-OH and H-(60–121)-OBzl, in CHL/TFE (3:1, v/v) using water-soluble carbodiimide in the presence of HOOBt as coupling reagents. After removal of the protecting groups by HF followed by treatment with Hg(OAc)₂ in 50% acetic acid, the fully deprotected peptide was subjected to the oxidative folding reaction. The final product was confirmed to have the correct disulphide structure from its tryptic peptide mapping and to possess the same biological activities as those of the natural product. In order to clarify the active region of the hMK molecule, the N-terminal and C-terminal half domains [(1–59) and (60–121)] were also synthesized by the same procedure used for the hMK synthesis. The C-half domain was confirmed to show the full pattern of bioactivities except for the neuronal cell survival activity, while the N-half one showed much less activity in general.     

Rapid solid-phase peptide synthesis using thermal and controlled microwave irradiation.

A rapid and efficient microwave-assisted solid-phase synthesis method is described for the preparation of the nonapeptide WDTVRISFK, using conventional Fmoc/Bu(t) orthogonal protection strategy. The synthesis protocol is based on the use of cycles of pulsed microwave irradiation with intermittent cooling of the reaction during the removal of the Fmoc protecting group and during the coupling. The desired nonapeptide was obtained in highest yield and purity by employing MicroKan technology. The chemical reactions were carried out in a single-mode microwave reactor, equipped with a fiber-optic probe to monitor the reaction temperature continuously.