1. Introduction to Nematology 作者 B.G. Chitwood and M.B. Chitwood，最早一本综合系统的线虫学书籍，五十年代出版。作者业界名气很大，目前根结线虫里面一个非常重要的检疫性线虫就是以他命名的(Meloidogyne chitwoodi) 2. General Nematology 作者：Armand Maggenti，UCD 教授，现已退休，研究线虫范围较广，植物寄生，动物寄生，腐生都有涉及，最有名的是他六十年代根据不同类群食道结构所构建的进化树。此书图非常精美，是一个经典之作。 3. The structure of Nematodes 作者：Alan F. Bird Jean Bird，线虫细微结构方面最经典的著作。运用大量绘图和电镜照片，仔细阅读后会发现能够解决你很多结构上的困惑。缺点是实在太专业，里面动物学术语太多太精细，对于绝大多数只需要掌握常见普通结构的读者来说只会越读越糊涂。 对于一般结构的了解，推荐Frida Decreamer编辑的线虫形态学教材。 4. The Biology of Nematodes 作者 Donald Lee，很新的一本书，2002年出版。很多人推荐，但还没看过 5.Nematodes: structure, development, classification and phylogeny 作者 Malakhov,V.V，好像有好几版，我见过的是蓝色封皮的一本，但网上没找到合适的图。1994年出版，特点是加进去很多精细结构，轻分类学，种发育与结构。引用秀丽隐杆线虫细胞发育最新研究，是一本非常细致而专业的书籍。可惜此书极其不好买。 6. Nematology advances and perspectives 最近才出版的线虫学书籍，一共一和二两卷，本人虽然没看过但据说还挺不错，加进去很多生理学研究，而且作者是两个中国人，在美国也很有名气，实在难得，所有必须得支持下。
老化的原因仍然是难以捉摸的 诸平 据 MedicalXpress 网站 2014 年 10 月 22 日 报道，德国波恩大学（ University of Bonn ） 、 德国海德堡癌症研究中心（ German Cancer Research Center Heidelberg ）以及英国剑桥医学研究委员会（ Medical Research Council in Cambridge, England ）的科学家领导的有来自9个国家28位专家参与的研究结果， 对于中国学者关于老化问题的研究结果持有不同的观点，认为老化的原因仍然是难以捉摸的。 2014 年 2 月 12 日 ，北京生命科学研究所董梦秋（ Meng-Qiu Dong ）实验室与北大分子医学研究所程和平（ Heping Cheng ）实验室在《自然》（ Nature ， DOI:10.1038/nature13012 ）杂志在线发表题为 “Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans ” 的文章，报道了线粒体的 “ 超氧炫 ” 频率可以预测线虫的寿命—— En-Zhi Shen , Chun-Qing Song , YuanLin , Wen-Hong Zhang , Pei-Fang Su , Wen-Yuan Liu , Pan Zhang , Jiejia Xu , Na Lin , Cheng Zhan , Xianhua Wang , Yu Shyr , Heping Cheng Meng-Qiu Dong . Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans . Nature 508 , 128- 132 （ 2014 ); doi:10.1038/nature13012 . 在这篇文章中，作者借助程和平课题组在 2008 年发现的线粒体超氧探针 cp-YFP ，直接观察单个线粒体内超氧阴离子自由基的自发的、爆发性的生成，即线粒体 “ 超氧炫 ” 现象。已知细胞内超氧炫的频率与线粒体呼吸、 ATP 合成、钙信号、基础活性氧水平等紧密相关，那么在衰老过程中，线粒体超氧炫怎么变化呢？作者从成虫第 1 天连续观察到第 19 天，惊讶地发现野生型线虫咽部肌肉细胞的超氧炫频率在第 2 ～ 3 天和第 8.5 ～ 9.5 天出现 2 个峰值，恰好分别对应线虫的生育高峰期和开始有个体死亡的阶段。对于长寿或者短寿的突变体线虫，这 2 个峰的位置和强度都有特征性变化，暗示了线粒体的功能活性与衰老有着密切关系。决定寿命的因素分为三类，即基因、环境和随机因素。《自然》杂志发表的这篇文章的作者发现，三类因素对线虫寿命的影响都可以通过成虫第 3 天咽部肌肉细胞的超氧炫频率反映出来。第 3 天的超氧炫频率与寿命负相关，而第 9 天的超氧炫频率与寿命没有相关性。线虫成虫第 3 天的超氧炫频率作为线粒体的机能状态参量可以预测寿命长短变化是一个出人意料的发现。这意味着，在动物机体功能最旺盛的时候，衰老的速度在相当大程度上已经决定了，虽然年轻时设立的衰老轨迹在后期仍然有机会被修改。该发现提示衰老是生物体程序调控的过程，与线粒体的功能活动密切相关。这篇文章的结果对于衰老研究的理论意义在于：首先，它支持广义的线粒体衰老学说，即线粒体是遗传、环境和随机因素调控衰老的一个重要节点；同时，也为程序化衰老学说（ programmed theories of aging ）提供了可能是迄今为止最有说服力的实验证据。前者有关个体衰老的原因，后者有关物种寿命的自然选择与进化。对于线虫之外的其它动物，年轻成体的线粒体超氧炫频率与寿命的负相关性是否成立，以及相关性背后的生物学机制等问题都亟待进一步研究。 北京生命科学研究所博士研究生申恩志（ En-Zhi Shen ）、宋春青（ Chun-Qing Song ，中国农业大学学籍）和北京大学博士研究生林渊（ Yuan Lin ）为此文的共同第一作者。通讯作者为董梦秋和程和平。台湾国立成功大学的苏佩芳（ Pei-Fang Su ）和范德堡大学（ Vanderbilt University ）的石瑜教授（ Yu Shyr ）主持了数据的统计分析。北京生命科学研究所所影像中心的刘文苑（ Wen-Yuan Liu ）和占成（ Cheng Zhan ）博士在图形数据的处理方面提供了很多支持。此文其他作者还有董梦秋实验室的张文红（ Wen-Hong Zhang ）、张攀（ Pan Zhang ），程和平实验室的林娜（ Na Lin ）、徐杰佳（ Jiejia Xu ）和王显花（ Xianhua Wang ）。这项研究得到了科技部、国家自然科学基金和北京市的资助。 这篇论文使全世界的专家为之震动， 文章中研究者认为他们似乎找到了老化的原因。但是，由波恩大学牵头的一个国际性的科学家小组最近对中国学者文章中提出的基本假设持有不同的观点 , 他们认为老化的原因仍然是一个难以捉摸的问题，相关研究结果于 2014 年 10 月 23 日 在 Nature 杂志网站发表 —— Markus Schwarzländer , Stephan Wagner , Yulia G. Ermakova , Vsevolod V. Belousov , Rafael Radi , Joseph S. Beckman , Garry R. Buettner , Nicolas Demaurex , Michael R. Duchen , Henry J. Forman , Mark D. Fricker , David Gems , Andrew P. Halestrap , Barry Halliwell , Ursula Jakob , Iain G. Johnston , Nick S. Jones , David C. Logan , Bruce Morgan , Florian L. Müller , David G. Nicholls , S.James Remington , Paul T. Schumacker , Christine C. Winterbourn , Lee J. Sweetlove et al. The ‘mitoflash’ probe cpYFPdoes not respond to superoxide. Nature 514, E12–E14 (23 October 2014). doi: 10.1038/nature13858 . 其摘要如下： Ageingand lifespan of organisms are determined by complicated interactions betweentheir genetics and the environment, but the cellular mechanisms remaincontroversial; several studies suggest that cellular energy metabolism and freeradical dynamics affect lifespan, implicating mitochondrial function. Recently,Shen et al. 1 providedapparent mechanistic insight by reporting that mitochondrial oscillations of‘free radical production’, called ‘mitoflashes’, in the pharynx of three-dayold Caenorhabditis elegans correlated inversely with lifespan.The interpretation of mitoflashes as ‘bursts of superoxide radicals’ assumesthat circularly permuted yellow fluorescent protein (cpYFP) is a reliableindicator of mitochondrial superoxide 2 , but this interpretation has beencriticized because experiments and theoretical considerations both show thatchanges in cpYFP fluorescence are due to alterations in pH, not superoxide 3 , 4 , 5 , 6 , 7 . Here we show that purified cpYFP iscompletely unresponsive to superoxide, and that mitoflashes do not reflectsuperoxide generation or provide a link between mitochondrial free radicaldynamics and lifespan. There is a Reply to this Brief Communication Arising by Cheng, H. et al. Nature 514, http://dx.doi.org/10.1038/nature13859 (2014). 更多信息请浏览原文。
美国哥伦比亚大学医学院的研究人员今天在Cell发表最新研究论文，详细披露了长辈动物饥饿对后辈动物寿命的影响。在线虫中的研究结果表明，父母挨饿，子女长寿，而且此效应可以延续3代。也就是太爷爷、太奶奶挨饿，重孙儿、重孙女还能长寿。 研究显示，挨饿导致的长寿效应不涉及任何基因序列的改变，也就是属于“非孟德尔式遗传”，而是“拉马克式获得性遗传”，用现代术语表述则是“表观遗传”或称“外基因性状”（epigenetic traits）。 研究人员发现，饥饿的线虫体内积累了一些能影响营养相关基因表达的小干扰RNA（siRNA），它们 可通过生殖细胞跨代遗传给后代，并 在RDE-4和HRDE-1等蛋白质协助下表现延寿效果 。 这项研究进一步证实，先辈经历的快乐和痛苦都可以在后代中留下不可磨灭的印记，比如热量限制（饥饿）、精神创伤、疾病、口味等，现在看来都是可以遗传的。由此联想，获得性遗传现象也许大大推动了生物对环境的适应性进化。 Effects of starvation can be passed to future generations, through small RNAs apparently without DNA involvement Date: July 17, 2014 Source: Columbia University Medical Center Summary: A new study, involving roundworms, shows that starvation induces specific changes in so-called small RNAs and that these changes are inherited through at least three consecutive generations, apparently without any DNA involvement. Starvation in roundworms induces changes in small RNAs, resulting in the transmission of acquired traits to subsequent generations. Credit: Columbia University Medical Center Evidence from human famines and animal studies suggests that starvation can affect the health of descendants of famished individuals. But how such an acquired trait might be transmitted from one generation to the next has not been clear. A new study, involving roundworms, shows that starvation induces specific changes in so-called small RNAs and that these changes are inherited through at least three consecutive generations, apparently without any DNA involvement. The study, conducted by Columbia University Medical Center (CUMC) researchers, offers intriguing new evidence that the biology of inheritance is more complicated than previously thought. The study was published in the July 10 online edition of the journal Cell . The idea that acquired traits can be inherited dates back to Jean Baptiste Larmarck (1744-1829), who proposed that species evolve when individuals adapt to their environment and transmit the acquired traits to their offspring. According to Lamarckian inheritance, for example, giraffes developed elongated long necks as they stretched to feed on the leaves of high trees, an acquired advantage that was inherited by subsequent generations. In contrast, Charles Darwin (1809-82) later theorized that random mutations that offer an organism a competitive advantage drive a species' evolution. In the case of the giraffe, individuals that happened to have slightly longer necks had a better chance of securing food and thus were able to have more offspring. The subsequent discovery of hereditary genetics supported Darwin's theory, and Lamarck's ideas faded into obscurity. However, events like the Dutch famine of World War II have compelled scientists to take a fresh look at acquired inheritance, said study leader Oliver Hobert, PhD, professor of biochemistry and molecular biophysics and a Howard Hughes Medical Institute Investigator at CUMC. Starving women who gave birth during the famine had children who were unusually susceptible to obesity and other metabolic disorders, as were their grandchildren. Controlled animal experiments have found similar results, including a study in rats demonstrating that chronic high-fat diets in fathers result in obesity in their female offspring. In a 2011 study, Oded Rechavi, a postdoctoral fellow in Dr. Hobert's laboratory, found that roundworms (C. elegans) that developed resistance to a virus were able to pass along that immunity to their progeny for many consecutive generations. The immunity was transferred in the form of small viral-silencing RNAs working independently of the organism's genome. Other studies have reported similar findings, but none of these addressed whether a biological response induced by natural circumstances, such as famine, could be passed on to subsequent generations. To address this question, Dr. Hobert's team starved roundworms for six days and then examined their cells for molecular changes. The starved roundworms, but not controls, were found to have generated a specific set of small RNAs. (Small RNAs are involved in various aspects of gene expression but do not code for proteins.) The small RNAs persisted for at least three generations, even though the worms were fed normal diets. The researchers also found that these small RNAs target genes with roles in nutrition. Since these small RNAs are produced only in response to starvation, they had to have been passed from one generation to another. We know from other studies that small RNAs can be transported from cell to cell around the body, said Dr. Hobert. So, it's conceivable that the starvation-induced small RNAs found their way into the worms' germ cells -- that is, their sperm or eggs. When the worms reproduced, the small RNAs could have been transmitted generationally in the cell body of the germ cells, independent of the DNA. The study also found that the progeny of the starved worms had a longer life span than the progeny of the controls. We have not shown that the starvation-induced small RNAs were responsible for the increased longevity -- it's just a correlation, said Dr. Hobert. But it's possible that these small RNAs provided a means for the worms to control the expression of relevant genes in later generations. The findings have no immediate clinical application. However, they do suggest that we should be aware of other things -- beyond pure DNA changes -- that may have a long-term impact on the health of an organism, said Dr. Hobert. In other words, something that happened to one generation, whether famine or some other traumatic event, may be relevant to the health of its descendants for generations. Story Source: The above story is based on materials provided by Columbia University Medical Center . Note: Materials may be edited for content and length. Journal Reference : Oded Rechavi, Leah Houri-Ze’evi, Sarit Anava, Wee Siong Sho Goh, Sze Yen Kerk, Gregory J. Hannon, Oliver Hobert. Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans . Cell , 2014; DOI: 10.1016/j.cell.2014.06.020
5月14日，Nature在线发表了“代谢物α-酮戊二酸通过抑制ATP合酶及TOR延长寿命”，由来自美国洛杉矶加州大学及哈佛大学的数十位作者联名发表，从姓名拼写法看，有多位华裔人士参与研究，其中通讯作者肯定是华人（Jing Huang）。以下是该文的题目和摘要： The metabolite α-ketoglutarate extends lifespan by inhibiting ATP synthase and TOR Nature (2014) doi:10.1038/nature13264Received 03 October 2012 Accepted 17 March 2014 Published online 14 May 2014 Metabolism and ageing are intimately linked. Compared with ad libitum feeding, dietary restriction consistently extends lifespan and delays age-related diseases in evolutionarily diverse organisms 1 , 2 . Similar conditions of nutrient limitation and genetic or pharmacological perturbations of nutrient or energy metabolism also have longevity benefits 3 , 4 . Recently, several metabolites have been identified that modulate ageing 5 , 6 ; however, the molecular mechanisms underlying this are largely undefined. Here we show that α -ketoglutarate ( α -KG), a tricarboxylic acid cycle intermediate, extends the lifespan of adult Caenorhabditis elegans . ATP synthase subunit β is identified as a novel binding protein of α -KG using a small-molecule target identification strategy termed drug affinity responsive target stability (DARTS) 7 . The ATP synthase, also known as complex V of the mitochondrial electron transport chain, is the main cellular energy-generating machinery and is highly conserved throughout evolution 8 , 9 . Although complete loss of mitochondrial function is detrimental, partial suppression of the electron transport chain has been shown to extend C. elegans lifespan 10 , 11 , 12 , 13 . We show that α -KG inhibits ATP synthase and, similar to ATP synthase knockdown, inhibition by α -KG leads to reduced ATP content, decreased oxygen consumption, and increased autophagy in both C. elegans and mammalian cells. We provide evidence that the lifespan increase by α -KG requires ATP synthase subunit β and is dependent on target of rapamycin (TOR) downstream. Endogenous α -KG levels are increased on starvation and α -KG does not extend the lifespan of dietary-restricted animals, indicating that α -KG is a key metabolite that mediates longevity by dietary restriction. Our analyses uncover new molecular links between a common metabolite, a universal cellular energy generator and dietary restriction in the regulation of organismal lifespan, thus suggesting new strategies for the prevention and treatment of ageing and age-related diseases. 这项研究是在线虫和哺乳动物培养细胞系中做的。文章的大意是：三羧酸循环中间产物α-酮戊二酸可以延长线虫的寿命，其原理在于它能结合到ATP合酶的β亚基上，并抑制其ATP合成活性，这一结果已通过“药物亲和性响应靶点稳定性”（DARTS）的分子靶点技术加以鉴定。在线虫和哺乳动物细胞中，像ATP合酶基因敲除一样，随着ATP含量降低，氧消耗减少，自噬增加。同时，这种效应还要依赖下游的雷帕霉素靶点（TOR）。在饥饿时，体内α-酮戊二酸含量水平升高，而α-酮戊二酸并不能升高热量限制 （calorie restriction） 动物的寿命，说明α-酮戊二酸是热量限制导致延寿的关键代谢物。 根据现有的长寿理论，长寿相关的一系列代谢变化是由线粒体启动的，而启动此过程的关键信号是ATP与NAD+的减少，前者导致AMP/ATP比值升高，直接激活AMPK，后者导致NAD+/NADH比值升高，用来激活SIRT1，并与AMPK共同激活PGC-1α，其结果是促进线粒体增殖和呼吸活动增强。在此过程中，抗氧化系统整体活化，活性氧逐渐减少，细胞代谢活动模式改变，具体表现在合成代谢相对减弱，分解代谢相对增强。 这项最新研究的突出成果是首次鉴定出热量限制减少ATP合成的关键是α-酮戊二酸增加，而且将调控的靶点精确定位在ATP合酶上，的确非常有创意。除了热量限制之外，任何能导致线粒体解偶联（mitochondrial uncoupling）的因素都能引起ATP合成减少，因而都能发挥延寿效应。此前有报道称，线粒体解偶联剂2,4-二硝基苯酚能通过质子泄漏的机制使ATP合成减少，可以在小鼠中发挥长寿效应。 不过，在食物中添加或直接服用 α-酮戊二酸并不会在人体中产生长寿效果，因为三羧酸循环发生在线粒体中， α-酮戊二酸及其靶点ATP合酶也都存在于线粒体内。目前，最好的非药物长寿良方就是热量限制，药物方面曾报道雷帕霉素、白藜芦醇等具有延寿效果，但仍在继续探索。这篇论文描述的是线虫研究结果，在培养基中添加 α-酮戊二酸可以使体内 α-酮戊二酸升高50%，说明线虫生物膜上存在一种运输 α-酮戊二酸的分子 机制。 最近，我们在酿酒酵母中完成了一项有关热量限制及其模拟物（青蒿素、过氧化氢）诱导长寿及其作用机理的研究，发现热量限制、青蒿素、过氧化氢都能通过一氧化氮介导线粒体解偶联，然后诱导线粒体增殖，最后导致酵母寿命延长，我们把青蒿素、过氧化氢这类有毒物质在低浓度时导致的生命长寿现象归因于“低毒兴奋效应”（hormesis），并验证了呼吸代谢“先升后降”的“双期”模式（研究结果已投给《中国科学—生命科学》英文版，现已通过二审）。 总之，生命长寿的逻辑其实很简单，就是尽量增加繁殖后代的机会。当营养丰富时，可以最大限度地生殖，不必长寿；而饥饿时，必须延长自己的生存期，等待营养再度丰富，以便增加成功交配、孕育和抚育后代的机会。 附：Nature论文首页预览（ http://www.readcube.com/articles/10.1038/nature13264?utm_campaign=readcube_accessutm_source=nature.comutm_medium=purchase_optionutm_content=thumb_version ）
原文：Susanne Wurst, Sander van Beersum, Roel Wagenaar, Tanja Bakx-Schotman, Barbara Drigo, Ingar Janzik, Arnaud Lanoue, Wim H. van der Putten. Plant defence against nematodes is not mediated by changes in the soil microbial community. Functional Ecology, 2009, 23 (3): 488-495. 1. Indirect plant defence, the recruitment of antagonists of herbivores, is well-known above the ground. In spite of various soil microorganisms acting as antagonists to root herbivores, it is still largely unknown whether plants can promote antagonistic microorganisms as an indirect defence mechanism. 2. In a greenhouse study we examined whether soil microorganisms could mediate plant defence against plant-feeding nematodes. Growth, nutrient contents and root exudation of three plant species ( Plantago lanceolata , Holcus lanatus , Lotus corniculatus ) and the performance of nematodes and fungal communities in the rhizospheres were measured. 3. The plant species differed in their effects on plant-feeding nematodes; however, the addition of soil microorganisms did not enhance nematode control. Nematode addition changed root exudation patterns and rhizosphere fungal community structure in a plant species-specific manner. Glucose levels in the root exudates of all three examined plant species were enhanced, and P. lanceolata root exudates contained higher levels of fumaric acid when nematodes had been added. 4. We conclude that nematodes have plant species-specific effects on root exudate chemistry and rhizosphere fungal community composition, but these effects do not necessarily enhance indirect control of nematodes by antagonistic microorganisms. More studies on below-ground plant defence are definitely needed. 注：传统上地下生态学过程往往被处理为一个黑箱，随着研究方法的发展以及地下生态过程的揭示，不得不让我们重新反思或重新认识各种生态过程，特别是营养级相互关系，top-down和bottom-up效应。特定种类的食根线虫会改变植物根际分泌物的组分，进一步影响根际微生物群落组成和结构；而微生物群落的改变，是否也改变了作为植食者天敌的间接效应，这些都还有待于进一步的研究。
标签: 线虫
