生物毒素的医药应用研究进展

生物毒素是一大类具有重要意义的生物源化学物质,生物毒素研究已发展成为与多种学科交叉的“生物毒素学”新学科,其发展对于生命科学、生源合成化学、化学生物学、化学生态学、医学、药物学都有重要意义,对药物创新研究更具有积极作用。该文概述了生物毒素的种类,详细阐述了生物毒素的医药应用及最新进展,指出了生物毒素在医药研究上的热点。     

生物毒素的应用研究

概述了生物毒素对人类以及农业、畜牧业和海洋渔业的危害,并阐述了生物毒素在生物学、药学、医学及军事科学中的应用研究现状及最新进展;同时对生物毒素研究的发展趋势进行了分析,这将为生物毒素的合理开发利用奠定基础。     

生物毒素研究新进展

生物毒素总的来说是有害的,可使生命有机体得病,重者死亡。某些原核生物和真核生物或某些低等生物和高等生物均有产生毒素的能力。美国一位生理学家曾做过实验,证实人生气时会分泌毒素。把人生气时呼出的“生气水”注射到大白鼠身上,几分钟后大白鼠就死亡了。生气时的分泌物比任何情绪时都复杂,更具有毒性。生物毒素固然有其害,但同时亦有其利,“以毒攻毒”,可用于治病。因此,     

“中国生物产业大会·2007”基本概况

大会名称：中文名称：中国生物产业大会·2007 英文名称：Bioindustry Convention of China．2007 中文简称：规范简称“生物产业大会”     

检索表式观察法在生物教学中的实践和探索

《生物学》中有很多形态结构相似的生物和生理功能密切相关的内容,按照传统教学法,学生记忆负担繁重,且容易混淆。教学中,我借鉴二歧分类法两相比较,非此即彼的原则,采用检索表式观察法,即通过指导学生“观察→比较观察→抽象概括→实践应用”寻求生物间形态结构和生理功?..     

LASER - Bio 2015＇ Fuzhou中国遗传学会第十二届全国激光生物学学术会议第一轮通知

为了推进激光生命科学发展,促进全国生物学的研究与交流,中国遗传学会拟于2015年4月24-27日在福州举办“第十二：届全国激光生物学学术会议”。本次大会将邀请我国激光生物学领域的知名专家学者作专题报告,大会将探讨我国激光生物学研究的新思想、新方法、新技术,促进本学科领域的协同发展。会议由医学光电科学与技术教育部重点实验室（福建师范大学）、中国遗传学会《激光生物学报》编辑部承办,华南师范大学生物光子学研究院、激光生命科学教育部重点实验室（华南师范大学）、生物医学光子学教育部重点实验室（华中科技大学）、湖南师范大学生命科学学院协办,会议论文的审稿、录取、出版由《激光生物学报》编辑部负责。会议期间还将组织与会代表考察福建师范大学医学光电科学与技术教育部重点实验室,以及福建师范大学杰出校友、美国科学院院士陈志坚教授创建的“福建师范大学南方生物医学研究中心”。     

生物成矿作用与生物矿化作用

列举５５种生物矿物，其中包括氧化物，含氧盐，水化物，羟基化物，钙化合物，指出它们通常经历非晶质、过渡、成熟和石化等４个相阶段。根据生物矿物体的元素丰度顺序与岩石圈和生物圈对比，将生矿元素分为６类。提出生矿元素保留于生物体内８种形式，即可溶无机化合物、有机络合物、生矿粒、生矿簇、骨针、骨片、骨壳和骨骼，并以磷为例阐明了生矿元素的富集过程。按照生物作用型式，建议划分生物矿床为堆积、粘结、吸附和储集４种成因类型，分别讨论它们成矿的生物、矿物和矿床，分析形成的环境、过程和阶段，并介绍中国某些著名生物矿床实例。最后总结了生物矿床的地史演化趋向：金属硫化物矿床→条带状硅铁（锰）粘结矿床→叠层状白云岩粘结矿床→磷酸盐和碳酸锰粘结矿床→铅锌和油气储集矿床→煤和油气。     

战争和恐怖行动时使用的微生物、生物和化学武器(上)

战争和恐怖行动时使用微生物、生物和化学武器已有较长的历史。例如,早在1917～1918年德国曾在一战中使用氯气、光气和硫芥。20世纪30年代日本曾对中国东北地区(满洲)的“囚犯”使用肉毒杆菌毒素。1975～1981年老挝、柬埔寨和阿富汗的“黄雨”事件中,曾使用单端孢霉菌毒素T-2。1978年保加利亚流亡者Georgi Markov在伦敦被注     

多方协作，共商生物产业发展大计——“中国生物产业大会·2007”将于6月在石家庄召开

我国生物技术领域首次面向产业发展的大会——“中国生物产业大会·2007”将于2007年6月16～18日在石家庄召开。本次大会将围绕“创新与发展,战略与未来”的主题,邀请政府官员、科学家、企业家以及来自国内外投资者共商我国生物产业发展大计,共同推进我国生物产业持续、健康、快速发展。     

微囊藻毒素生物治理技术研究进展*

近年来,随着全球气候变暖和水体富营养化程度加深,蓝藻水华频繁暴发。微囊藻毒素是有害蓝藻产生及释放的危害最大的一类蓝藻毒素,对生态环境和公众健康造成了严重的威胁。因此,寻求有效的微囊藻毒素降解方法已成为全球科学领域的研究热点。针对微囊藻毒素生物治理技术展开综述,阐述了微囊藻毒素的产生、理化性质及生物毒性,总结了微生物、水生植物、浮游动物等自然生物降解微囊藻毒素的能力。在此基础上概述了生物滤池、人工湿地、生态浮床、膜生物膜反应器等生物治理技术对微囊藻毒素的去除效果,分析了现有微囊藻毒素生物处理方法的优势和局限性,并对今后的研究方向提出展望,为解决水环境中微囊藻毒素的污染问题提供思路。     

Drugs from slugs—Past,present and future perspectives of ω-conotoxin research

Peptides from the venom of carnivorous cone shells have provided six decades of intense research, which has led to the discovery and development of novel analgesic peptide therapeutics. Our understanding of this unique natural marine resource is however somewhat limited. Given the past pharmacological record, future investigations into the toxinology of these highly venomous tropical marine snails will undoubtedly yield other highly selective ion channel inhibitors and modulators. With over a thousand conotoxin-derived sequences identified to date, those identified as ion channel inhibitors represent only a small fraction of the total. Here we discuss our present understanding of conotoxins, focusing on the ω-conotoxin peptide family, and illustrate how such a seemingly simple snail has yielded a highly effective clinical drug.     

Small peptides, big world: biotechnological potential in neglected bioactive peptides from arthropod venoms.

Until recently, a toxinologist's tasks involved the search for highly toxic or lethal toxins in animal venoms that could explain the harmful effects in clinically observed symptoms. Most of these toxins were put on evidence using a function to structure approach, in which a biological phenomena observation usually guided the isolation and characterization of the causative molecule. Paving this way, many toxins were promptly purified because of their readily observed effect. Nevertheless, small molecules with micro-effects that are not easily visualized can be relatively neglected or poorly studied. This situation has changed now with the advent of the sensitivity, resolution and accuracy of techniques such as mass spectrometry and proteomic approaches used in toxinology. Taking advantage of these methodologies, small peptides with 'newly exploited' biological activities such as vasoactive, hormone-like, antimicrobial and others have been recently given much more attention, enlarging the known repertoire of bioactive molecules found in animal venoms. This article aims to review current knowledge on small biologically active peptides (<3 kDa) found in arthropod venoms and discuss their potentialities as new drug candidates or therapeutic lead compounds.     

Cryptides: buried secrets in proteins

The proteome originally described the entire set of proteins expressed by a genome, tissue or organism. Subsequently this term was limited to all the expressed proteins at a given time under defined conditions. Hence, specializations such as functional proteome, cancer proteome, liver proteome and so forth have arisen. One particular proteome that has been recently described is the cryptome, a unique subset of already known proteins that has the ability of generating bioactive peptides and proteins when submitted to proteolytic cleavage, rather than the classical processing pathways. This is an idea in agreement with the concept that evolution is not related to the amount of genes or putative proteins that could be secreted by an organism, but to the way these proteins are processed. These ‘new’ molecules may have related or increased properties when compared to the ‘original’ molecule or possess completely unrelated biological effects, thus increasing the array of biological roles that can be associated to one given protein (or gene). In this work, we review this recent concept and put it into the toxinology field as well, an area in which the diversity of functional molecules (and roles) is essential for the survival of a given organism.     

Structural and functional properties of Bp-LAAO,a new l-amino acid oxidase isolated from Bothrops pauloensis snake venom

An l-amino acid oxidase (Bp-LAAO) from Bothrops pauloensis snake venom was highly purified using sequential chromatography steps on CM-Sepharose, Phenyl-Sepharose CL-4B, Benzamidine Sepharose and C18 reverse-phase HPLC. Purified Bp-LAAO showed to be a homodimeric acidic glycoprotein with molecular weight around 65 kDa under reducing conditions in SDS-PAGE. The best substrates for Bp-LAAO were l-Met, l-Leu, l-Phe and l-Ile and the enzyme showed a strong reduction of its catalytic activity upon l-Met and l-Phe substrates at extreme temperatures. Bp-LAAO showed leishmanicidal, antitumoral and bactericidal activities dose dependently. Bp-LAAO induced platelet aggregation in platelet-rich plasma and this activity was inhibited by catalase. Bp-LAAO-cDNA of 1548 bp codified a mature protein with 516 amino acid residues corresponding to a theoretical isoelectric point and molecular weight of 6.3 and 58 kDa, respectively. Additionally, structural and phylogenetic studies identified residues under positive selection and their probable location in Bp-LAAO and other snake venom LAAOs (svLAAOs). Structural and functional investigations of these enzymes can contribute to the advancement of toxinology and to the elaboration of novel therapeutic agents.     

Toxins that Modulate Ionic Channels as Tools for Exploring Insulin Secretion

Glucose-induced insulin secretion is a cardinal process in glucose homeostasis and metabolic expenditure. Uncoupling of the insulin response to glucose variations may lead to type-2 diabetes mellitus. Thus the identification of more specific drugs to facilitate the study of insulin secretion mechanisms and to develop new pharmacological agents for therapeutics is fundamental. Venomous organisms possess a great diversity of toxic molecules and some of them are neurotoxins that affect membrane excitability. This article reviews properties of those toxins affecting ion channels pivotal for insulin secretion and the usefulness of such compounds in the study of pancreatic beta-cell physiology. Here we examine the major contributions of toxinology to the understanding of the ionic phase of insulin secretion, to the determination of ion channel composition in different insulin secreting cell-line models as well as from primary cultures of different mammal species. Finally, we present a summary of the many diverse toxins affecting insulin release and a brief discussion of the potential of novel toxins in therapeutics.     

Matrix biology meets toxinology

Venoms are cocktails containing pharmacologically active compounds, which drastically affect essential functions of the neuromuscular and cardiovascular system, as well as of blood, kidney and other organs. As the extracellular matrix and its contacts with cells are responsible for maintaining the integrity and functionality of these organs and tissues, it is not surprising that several venom components target matrix molecules and their respective cellular receptors. Many venom components, such as matrix-degrading enzymes, disintegrins, and C-type lectin-like proteins, have been identified and have laid the foundation for the frontier research field of matrix toxinology. Interestingly, many toxins consist of domains which are structurally homologous to modules and domains of matrix proteins, their proteinases and cellular receptors. In addition to finding new agents and tools, which specifically interact with matrix molecules and their receptors, the characterization of known matrix-targeting toxins will provide insights into their molecular modes of action and thus may lead to potential new therapeutic strategies for treating matrix-related diseases, such as blood clotting and thrombocyte-mediated disorders, but also tumor malignancies.     

A multifaceted analysis of viperid snake venoms by two-dimensional gel electrophoresis: an approach to understanding venom proteomics

The complexity of Viperid venoms has long been appreciated by investigators in the fields of toxinology and medicine. However, it is only recently that the depth of that complexity has become somewhat quantitatively and qualitatively appreciated. With the resurgence of two-dimensional gel electrophoresis (2-DE) and the advances in mass spectrometry virtually all venom components can be visualized and identified given sufficient effort and resources. Here we present the use of 2-DE for examining venom complexity as well as demonstrating interesting approaches to selectively delineate subpopulations of venom proteins based on particular characteristics of the proteins such as antibody cross-reactivity or enzymatic activities. 2-DE comparisons between venoms from different species of the same genus (Bothrops) of snake clearly demonstrated both the similarity as well as the apparent diversity among these venoms. Using liquid chromatography/tandem mass spectrometry we were able to identify regions of the two-dimensional gels from each venom in which certain classes of proteins were found. 2-DE was also used to compare venoms from Crotalus atrox and Bothrops jararaca. For these venoms a variety of staining/detection protocols was utilized to compare and contrast the venoms. Specifically, we used various stains to visualize subpopulations of the venom proteomes of these snakes, including Coomassie, Silver, Sypro Ruby and Pro-Q-Emerald. Using specific antibodies in Western blot analyses of 2-DE of the venoms we have examined subpopulations of proteins in these venoms including the serine proteinase proteome, the metalloproteinase proteome, and the phospholipases A2 proteome. A functional assessment of the gelatinolytic activity of these venoms was also performed by zymography. These approaches have given rise to a more thorough understanding of venom complexity and the toxins comprising these venoms and provide insights to investigators who wish to focus on these venom subpopulations of proteins in future studies.     

Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa

The development of snake antivenoms more than a century ago should have heralded effective treatment of the scourge of snakebite envenoming in impoverished, mostly rural populations around the world. That snakebite still exists today, as a widely untreated illness that maims, kills and terrifies men, women and children in vulnerable communities, is a cruel anachronism. Antivenom can be an effective, safe and affordable treatment for snakebites, but apathy, inaction and the politicisation of public health have marginalised both the problem (making snakebite arguably the most neglected of all neglected tropical diseases) and its solution. For lack of any coordinated approach, provision of antivenoms has been pushed off the public health agenda, leading to an incongruous decline in demand for these crucial antidotes, excused and fed by new priorities, an absence of epidemiological data, and a poor regulatory framework. These factors facilitated the infiltration of poor quality products that degrade user confidence and undermine legitimate producers. The result is that tens of thousands are denied an essential life-saving medicine, allowing a toll of human suffering that is a summation of many individual catastrophes. No strategy has been developed to address this problem and to overcome the intransigence and inaction responsible for the global tragedy of snakebite. Attempts to engage with the broader public health community through the World Health Organisation (WHO), GAVI, and other agencies have failed. Consequently, the toxinology community has taken on a leadership role in a new approach, the Global Snakebite Initiative, which seeks to mobilise the resources, skills and experience of scientists and clinicians for whom venoms, toxins, antivenoms, snakes and snakebites are already fields of interest. Proteomics is one such discipline, which has embraced the potential of using venoms in bio-discovery and systems biology. The fields of venomics and antivenomics have recently evolved from this discipline, offering fresh hope for the victims of snakebites by providing an exciting insight into the complexities, nature, fundamental properties and significance of venom constituents. Such a rational approach brings with it the potential to design new immunising mixtures from which to raise potent antivenoms with wider therapeutic ranges. This addresses a major practical limitation in antivenom use recognised since the beginning of the 20th century: the restriction of therapeutic effectiveness to the specific venom immunogen used in production. Antivenomic techniques enable the interactions between venoms and antivenoms to be examined in detail, and if combined with functional assays of specific activity and followed up by clinical trials of effectiveness and safety, can be powerful tools with which to evaluate the suitability of current and new antivenoms for meeting urgent regional needs. We propose two mechanisms through which the Global Snakebite Initiative might seek to end the antivenom drought in Africa and Asia: first by establishing a multidisciplinary, multicentre, international collaboration to evaluate currently available antivenoms against the venoms of medically important snakes from specific nations in Africa and Asia using a combination of proteomic, antivenomic and WHO-endorsed preclinical assessment protocols, to provide a validated evidence base for either recommending or rejecting individual products; and secondly by bringing the power of proteomics to bear on the design of new immunising mixtures to raise Pan-African and Pan-Asian polyvalent antivenoms of improved potency and quality. These products will be subject to rigorous clinical assessment. We propose radically to change the basis upon which antivenoms are produced and supplied for the developing world. Donor funding and strategic public health alliances will be sought to make it possible not only to sustain the financial viability of antivenom production partnerships, but also to ensure that patients are relieved of the costs of antivenom so that poverty is no longer a barrier to the treatment of this important, but grossly neglected public health emergency.     

Purinergic signalling in the subretinal space: a role in the communication between the retina and the RPE

The retinal pigment epithelium (RPE) is separated from the photoreceptor outer segments by the subretinal space. While the actual volume of this space is minimal, the communication that occurs across this microenvironment is important to the visual process, and accumulating evidence suggests the purines ATP and adenosine contribute to this communication. P1 and P2 receptors are localized to membranes on both the photoreceptor outer segments and on the apical membrane of the RPE which border subretinal space. ATP is released across the apical membrane of the RPE into this space in response to various triggers including glutamate and chemical ischemia. This ATP is dephosphorylated into adenosine by a series of ectoenzymes on the RPE apical membrane. Regulation of release and ectoenzyme activity in response to light-sensitive signals can alter the balance of purines in subretinal space, and thus coordinate communication across subretinal space with the visual process.     

On the use of the Price equation

This paper distinguishes two categories of questions that the Price equation can help us answer. The two different types of questions require two different disciplines that are related, but nonetheless move in opposite directions. These disciplines are probability theory on the one hand and statistical inference on the other. In the literature on the Price equation this distinction is not made. As a result of this, questions that require a probability model are regularly approached with statistical tools. In this paper, we examine the possibilities of the Price equation for answering questions of either type. By spending extra attention on mathematical formalities, we avoid the two disciplines to get mixed up. After that, we look at some examples, both from kin selection and from group selection, that show how the inappropriate use of statistical terminology can put us on the wrong track. Statements that are 'derived' with the help of the Price equation are, therefore, in many cases not the answers they seem to be. Going through the derivations in reverse can, however, be helpful as a guide how to build proper (probabilistic) models that do give answers.