RNA interference: unraveling a mystery

Andrew Fire and Craig Mello have won the Nobel Prize in Medicine or Physiology for their discovery of RNA interference. Mary K. Montgomery, then a postdoc in the Fire laboratory, participated in some of the key experiments.     

Gene silencing by double-stranded RNA

Thanks to the Nobel Foundation for permission to publish this Lecture. We report here the Nobel Lecture delivered by Professor Andrew Z Fire. Together with the accompanying lecture by Professor Mello this lecture describes the exciting years leading to the discovery of RNA interference (RNAi) and some of the underlying molecular mechanisms. Professor Fire nicely points out his own contribution and the contribution of other research groups to the development of this field. He also presents an interesting discussion on the role of RNAi in immunity and challenges us with a number of open questions. The lecture ends presenting the great potential of exploiting RNAi for therapeutical purposes.     

Auxin und die apikale Dominanz

Der Nobelpreis für Physiologie oder Medizin 2006 geht an die Molekularbiologen Andrew Fire (Stanford University, USA) und Craig Mello (University of Massachusetts, USA) für die Entdeckung der RNA‐Interferenz im Fadenwurm Caenorhabditis elegans. Durch diesen Mechanismus können Gene spezifisch ausgeschaltet werden.     

RNAi from plants to nematodes

Coincident with the award of the Nobel Prize for Medicine in 2006 to Fire and Mello for their discovery of RNAi, plant scientists have succeeded in using RNAi-based techniques to control nematodes, a hitherto unmanageable plant parasite. Recent work has demonstrated that the expression in a host plant of double-stranded RNA targeting housekeeping or parasitism genes in the root-knot nematode resulted in resistance to nematode infection.     

RNA干涉与基因沉默

双链RNA介导的遗传干涉的机制是1998年发现的,它通过双链RNA的介导特异性地降解相应序列的mRNA,从而导致转录后水平的基因沉默,到目前为止的真菌,拟南芥,线虫,锥虫,水螅,涡虫,果蝇,斑马鱼,小鼠等真核生物中都发现存在这一基因沉默机制,目前的研究表明,RNA干涉与植物中的共抑制（Cosuppression),真菌中的基因压制（quelling)很可能具有共同的基本分子机制,这也说明,很可能在进化的很早期阶段,生物就获得了这种机制,RNA干涉对于抵抗病毒入侵,抑制转座子活动等具有重要作用,对于生物体的发育和基因调控可能也有重要作用。     

Molecular genetic tools in Toxoplasma and Plasmodium: achievements and future needs

The recent awarding of the Nobel prize to Andrew Fire and Craig Mello for the discovery of RNA-interference (RNAi) in plants once more demonstrated the importance of basic science in understanding biological mechanisms. Importantly, this discovery led to the establishment of powerful approaches to study gene function in a wide array of organisms. While a robust RNAi-technology remains elusive in apicomplexan parasites, other molecular genetic technologies have been introduced in recent years. Now, in the post genomic era, the task is to apply these methods to validate and functionally dissect an ever-expanding list of putative vaccine and drug candidates. The ultimate aim of such studies is to transform our knowledge of the genome to the knowledge of the phenome and ultimately new intervention strategies in these important pathogenic organisms. However, substantial limitations remain to the current repertoire of available molecular tools, which limits a comprehensive analysis of these candidates, especially of essential genes. This review summarises the methodologies available for functional gene analysis in apicomplexan parasites and discusses further needs in tool development.     

Revision and cladistic analysis of Isoctenus and description of a new neotropical genus (Araneae,Ctenidae, Cteninae)

A cladistic analysis was applied to test the monophyly of the genus Isoctenus. The data matrix comprised 28 taxa scored for 53 morphological and two behavioural characters. The analysis resulted in two equally parsimonious trees of 89 steps. The strict consensus was used to discuss the relationships of Isoctenus and related Cteninae genera. Ctenopsis Schmidt is synonymized with Isoctenus. Isoctenus foliifer Bertkau, I. strandi Mello‐Leitão, I. eupalaestrus Mello‐Leitão, I. janeirus (Walckenaer), I. coxalis (Pickard‐Cambridge), I. corymbus Polotow, Brescovit & Pellegatti‐Franco and I. malabaris Polotow, Brescovit & Ott are maintained in Isoctenus. Four species currently included in Ctenus are transferred to Isoctenus: I. griseolus (Mello‐Leitão) comb. nov., I. taperae (Mello‐Leitão) comb. nov., I. herteli (Mello‐Leitão) comb. nov. and I. minusculus (Keyserling) comb. nov. The following specific names are synonymized: Ctenus sanguineus Walckenaer, C. semiornatus Mello‐Leitão and Ctenopsis stellata Schmidt with Isoctenus janeirus (Walckenaer), Ctenus mourei Mello‐Leitão with Isoctenus herteli (Mello‐Leitão) and Ctenus pauper Mello‐Leitão with Isoctenus strandi Mello‐Leitão. Isoctenus sigma Schenkel, described from French Guiana, is transferred to Ctenus. Four species are newly described: Isoctenus areia sp. nov. from Paraíba, Brazil, I. charada sp. nov. and I. segredo sp. nov. from Paraná, Brazil, and I. ordinario sp. nov. from south and south‐eastern Brazil and north‐eastern Argentina. Isoctenus latevittatus Caporiacco is considered species inquirenda. Parabatinga gen. nov. is proposed to include Ctenus brevipes Keyserling. The following synonymies are established: Ctenus taeniatus Keyserling, C. tatarandensis Tullgren, C. anisitsi Strand, C. atrivulvus Strand, C. mentor Strand, C. brevipes brevilabris Strand, Isoctenus masculus Mello‐Leitão and Ctenus birabeni Mello‐Leitão with Parabatinga brevipes (Keyserling) comb. nov. © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 155 , 583–614.     

The role of cAMP and Ca on the modulation of junctional conductance: an integrated hypothesis

The role of cAMP and Ca in the modulation of junctional permeability is discussed. An integrated hypothesis is presented which proposes that cAMP modulates the junctional conductance through the activation of specific kinases and phosphorylation of gap junction proteins. A close-loop feed-back between cAMP and Ca is assumed to be relevant in the regulation of junctional conductance under physiological conditions. According to this hypothesis hormones modulate the junctional permeability through variations in the intracellular concentration of cAMP. It is known that in several tissues the cells are connected through low resistance intercellular junctions (Loewenstein, 1966; Bennett, 1973; De Mello, 1975, 1932a). Ions and small molecules can flow freely from cell-to-cell across narrow hydrophilic channels (De Mello, 1982a). This type of intercellular coupling is essential for the fast propagation of the impulse and the synchronization of electrical activity in excitable tissues (Bennett, 1973; De Mello, 1982a). It has been proposed that the exchange of chemical signals between cells is important for metabolic cooperation (Gilula et al. 1972) and growth control (Loewenstein, 1979). Therefore, the modulation of junctional conductance is a significant feature of cell biology. Evidence has been provided that the increase in free [Ca2+]i can produce cell decoupling in Chironomus salivary gland (Loewenstein et al., 1967) and in mammalian cardiac fibers (De Mello, 1972, 1975). The free [Ca2+]i required to suppress cell-to-cell coupling is difficult to determine because Ca ions are continuously taken up by mitochondria, sarcoplasmic reticulum or are extruded from the cell. In salivary gland a concentration of free [Ca2+]i of about 5-8 X 10(-5) M was found to be associated with cell decoupling (Loewenstein et al., 1967). The major difficulty here is that the concentration of the ion determined in the bulk of the cytosol is not necessarily the same near the gap junctions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Biogenesis of diverse plant phasiRNAs involves an miRNA-trigger and Dicer-processing

Journal of Plant Research - It has been almost 30 years since RNA interference (RNAi) was shown to silence genes via double-stranded RNAs (dsRNAs) in Caenorhabditis elegans (Fire et al....     

基因枪在RNA干扰中的应用研究进展

RNA干扰（RNA interference,RNAi）是指双链RNA（double-strand RNA,dsRNA）特异性降解同源mRNA,从而引发基因转录后水平沉默的现象,是一种高效、高特异性抑制基因表达的途径。自1998年Fire等发现RNA干扰现象以来,其特异性降解目的基因的优势吸引了众多研究者的目光。本文在简要综述RNAi技术在基因功能研究、抗病毒治疗,肿瘤基因治疗等领域的应用后,重点归纳了基因枪技术在RNAi研究即siRNA导入细胞中的应用,并简单分析其优势与意义。     

Fire exit is a potential four transmembrane protein expressed in developing Drosophila glia

Glia from many diverse organisms play a number of important roles during the development of the nervous system. Therefore, knowing the molecules that control glial cell function will further our understanding of the mechanisms that control nervous system development. We have isolated a novel gene in Drosophila melanogaster that is expressed in a subset of the peripheral glia. We call this gene "Fire exit" (Fie), as the glia that express this gene do so during a time when they mark the entry and exit point of axons at the CNS/PNS boundary. This subset of peripheral glia act as intermediate targets during pathfinding and migration of the sensory axons in particular. Fire exit has been cloned and found to encode a novel transmembrane protein. Fire exit belongs to a group of proteins identified in the Drosophila melanogaster and Anopheles gambiae databases which contain four predicted transmembrane domains and a shared intracellular motif. Mutations that remove the fire exit protein have no obvious disruption to glial function. On the other hand, glia expressing the Fire exit gene bridge the transition zone between CNS and PNS and play a role in sensory axon guidance. Therefore, it appears that, while the glia that express this protein mediate axon guidance, Fire exit itself plays a nonessential part in this function. A role for Fire exit in glial development may be suggested by its evolutionary relationship to a family of lysosome-associated proteins called LAPTMs and suggests that Fire exit may function in intracellular transport during glial development.     

Taxonomic review of Bourguyiinae,cladistic analysis,and a new hypothesis of biogeographic relationships of the Brazilian Atlantic Rainforest (Arachnida: Opiliones,Gonyleptidae)

The subfamily Bourguyiinae Mello‐Leitão, 1923 (Gonyleptidae) is revised, and both phylogenetic and biogeographic hypotheses are proposed. Bourguyiinae is monophyletic, and is the sister group of the remainder of the Gonyleptidae species used for analysis, except for the Metasarcinae, which collectively is the sister group of Metavononoides orientalis Mello‐Leitão, 1923 (Cosmetidae). Bourguyiinae is divided into two genera: Bourguyia (six species) and Asarcus (four species). The genus‐level synonyms proposed here are as follows: Caldasius, Styloleptes, and Stylopisthos are junior synonyms of Bourguyia; Bogdana, Cnemoleptes, and Opisthoplites are junior synonyms of Asarcus. The species synonyms proposed here are as follows: Afranius amarali Mello‐Leitão, 1934 is a junior synonym of Bourguyia albiornata Mello‐Leitão, 1923 ; Drastus hamatus Roewer, 1943 and Styloleptes conspersus Piza, 1943 are junior synonyms of Bourguyia trochanteralis Roewer, 1930 ; Asarcus corallipes Simon, 1879 , Asarcus lutescens Sørensen, 1884 , Asarcus pallidus Mello‐Leitão, 1923 , and Opisthoplites ypsilon Sørensen, 1884 are junior synonyms of Asarcus longipes Kollar in Koch, 1839 ; Asarcus nigriconspersus Soares & Soares, 1945 is a junior synonym of Asarcus ingenuus Melo‐Leitão, 1940. New species described are: Bourguyia bocaina sp. nov. (Serra da Bocaina, São José do Barreiro, São Paulo), Bourguyia vinosa sp. nov. (E.B. Boracéia, Salesópolis, São Paulo), and Asarcus putunaberaba sp. nov. (Parque Nacional do Caparaó, Alto Caparaó, Minas Gerais). Bourguyiinae is endemic to the Atlantic Rainforest in the Brazilian states of Minas Gerais, Rio de Janeiro, São Paulo, and Paraná. Based on the modified data matrix of Pinto‐da‐Rocha et al., we propose a new biogeographical hypothesis for the Atlantic Rainforest. We suggest that Bourguyiinae species were originally distributed from the coastal region of Paraná to the north of Rio de Janeiro and south‐east of Minas Gerais, with subsequent dispersals both to northern and southern areas. © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 156 , 319–362.     

Haematozoa of East African birds: II. Redescription of Haemoproteus centropi, a parasite of the Cuculidae

The avian haemoproteid, Haemoproteus centropi de Mello, a blood parasite found in members of the family Cuculidae, is redescribed from Clamator jacobinus Boddaert from Ngulia in Kenya. Haemoproteus froilanoi Tendeiro is considered to be a synonym of H. centropi. The reasons for this are discussed.     

Four Species of Theridiid Spider (Araneae) from Korea with a Description of New Species, Robertus naejangensis

Four species of the family Theridiidae, Robertus naejangensis sp. nov., Chrysso pulcherrima (Mello‐Leitao), Neottiura herbigrada (Simon) and Theridion longipalpum Zhu, are described with illustrations of their diagnostic features. The latter three species are newly recorded in the Korean spider fauna.     

植物-固定化菌剂联合修复多环芳烃污染土壤

以火凤凰根际土壤中发现的3种优势菌[分枝杆菌(Ⅰ)、产黄纤维单胞菌(Ⅱ)、少动鞘氨醇单胞菌(Ⅲ)]构建的多菌剂体系为供试菌剂,针对大港油田原油污染土壤,将固定化供试菌剂接种于修复植物火凤凰根际,探讨供试菌剂强化火凤凰修复多环芳烃(PAHs)污染土壤的效果。结果表明: 处理ⅠⅢ(有效活菌数为10⁹ cfu·mL^-1)和ⅠⅡⅢ(有效活菌数为10⁷ cfu·mL^-1)对PAHs的降解有促进作用,PAHs降解率分别为32.2%和41.4%,均显著高于相应对照处理。此外,处理ⅠⅡⅢ对火凤凰的地下生物量有明显促进作用,比对照处理增加了31.2%。表明由3种优势菌构建的多菌剂ⅠⅡⅢ可以作为火凤凰修复PAHs污染土壤的强化手段,为微生物强化植物修复技术提供了新的修复思路及方法。