扇贝大防御素和G型溶菌酶的基因克隆与重组表达

扇贝养殖是我国传统的海水养殖产业，但自1997 年以来，养殖扇贝陆续爆发的大规模死亡，不但造成了巨大的经济损失，而且严重影响了该产业的健康发展。扇贝病害的不断爆发以及病因的多样性迫切要求制定新的疾病防治措施和开发新型的抗菌物质。 从扇贝自身的免疫防御因子入手，筛选和克隆参与免疫防御的功能基因，一方面可以研究抗病功能基因在病原感染或环境胁迫条件下的表达规律，深入探讨扇贝的免疫防御机制，并可作为抗病良种选育的分子标记，指导扇贝的遗传改良和抗病品系的培育；另一方面，可对抗菌效应物实现重组表达，开发新型的病害预防治疗制剂，取代目前普遍使用的抗生素和化学药物。抗菌效应物是机体在免疫应答过程中产生的多肽类物质，对侵入生物体内的细菌、病毒具有很强的免疫杀灭作用，对抗菌效应物的研究有助于深入了解机体先天性免疫防御的机制。 本研究采用大规模EST测序方法，结合cDNA末端快速扩增（RACE）技术，从海湾扇贝血淋巴中克隆到了大防御素基因（big defensin, AiBD）的全长cDNA序列，该cDNA全长为531 bp，其中5' 非编码区（UTR）为24 bp，开放阅读框（Open Reading Frame, ORF）含有369 bp，编码122 个氨基酸残基；随后为138-bp 的3' UTR，包括一个多聚腺苷酸信号序列（AATAAA）和ploy A尾巴。分析表明，海湾扇贝大防御素是以前体的形式合成，前体分子包括信号肽、前域和成熟肽三部分。采用Northern blot方法，以DIG标记的DNA探针检测了 AiBD mRNA在不同组织中的表达。结果发现，AiBD 基因的转录本主要在血淋巴中表达，在鳃中也有微量的表达，而在外套膜、闭壳肌、性腺及肝胰腺中检测不到杂交信号。采用QRT-PCR（quantitative real time PCR）对鳗弧菌感染后海湾扇贝血淋巴中AiBD mRNA 的表达量进行了检测，结果发现在感染后8 h 内， AiBD mRNA 的相对表达量平缓升高；随着刺激时间的增长，AiBD基因的mRNA表达量急剧增加，在刺激后16 h 和32 h 分别达到了空白组的72.3 倍和131.1 倍。为了研究海湾扇贝大防御素的抗菌活性，将其成熟肽编码区克隆到毕赤酵母表达载体pPIC9K并实现了重组表达。抑菌实验表明，重组AiBD具有广谱的抗菌活性，其对供试的三株革兰氏阳性菌（藤黄微球菌、溶壁微球菌、金黄色葡萄球菌）都表现出显著的抗菌活性，而对革兰氏阴性菌（鳗弧菌、亮弧菌）的抑菌活性则相对较弱；此外，重组AiBD对表达宿主也表现出杀菌活性，证明其具有抗真菌活性。 根据栉孔扇贝G 型溶菌酶基因的cDNA序列，利用构建的Genome Walking 文库获得了栉孔扇贝G 型溶菌酶基因的全长序列，该基因序列全长为8131 bp，由六个外显子和五个内含子组成。六个外显子长度分别为55 bp，60 bp，90 bp，113 bp，145 bp 和140 bp；五个内含子的长度分别为1126 bp，2161 bp，2744 bp，750 bp和592 bp；内含子的两侧都具有RNA正确剪接所必需的识别位点（GT/AG）。利用TRANSFAC 软件对栉孔扇贝G 型溶菌酶基因的5' 侧翼序列分析发现，该基因的5' 侧翼具有 TATA box 和 CAAT box 的共有序列；此外，在该基因的5' 侧翼发现了C/EBP、NF-κB、OCT-1 和 NF-IL6 等参与免疫基因激活的转录因子潜在结合位点。采用Northern blot方法，以生物素标记的RNA 探针检测了栉孔扇贝G 型溶菌酶基因在不同组织中的表达。结果发现，该基因的转录本主要在鳃、性腺及肝胰腺中表达，在血细胞和外套膜中也有微量的的表达，而在闭壳肌中检测不到杂交信号，这表明栉孔扇贝G 型溶菌酶可能兼备参与机体免疫防御和消化的功能。为了研究栉孔扇贝G 型溶菌酶的抗菌活性，将其成熟肽编码区克隆到毕赤酵母表达载体pPIC9K并实现了重组表达。抑菌实验表明，重组产物具有显著的抗阳性菌活性，其对供试的藤黄微球菌、溶壁微球菌表现出明显的抑制作用，对金黄色葡萄球菌未检测到抑制活性；而对革兰氏阴性菌仅表现出微弱的抑菌活性（亮弧菌和鳗弧菌），对大肠杆菌则基本无抑制活性。

栉孔扇贝(Chlamys farreri)Toll样受体及其信号传递相关基因的克隆与表达

扇贝是我国海水养殖的重要品种，但自1994年以来，养殖扇贝陆续爆发的大规模死亡，不但造成了巨大的经济损失，而且直接威胁到现有产业的生存和发展。引起扇贝大规模死亡原因是多方面的，其主要原因是养殖环境恶化、扇贝种质衰退和抗病力下降。因此，深入研究扇贝免疫防御机制，探讨提高机体抗病力的有效途径和方法，改良种质和培育抗病品系，无疑是解决目前困扰扇贝养殖业健康可持续发展的必经之路。 Toll样受体（TLRs）家族是新近发现的模式识别受体（PRRs），参与识别病原体相关的分子模式（PAMPs），在天然免疫系统中起着非常重要的作用。哺乳动物中Toll样受体信号通路还参与诱导树枝状细胞成熟、参与免疫耐受、参与凋亡发生发展、介导非感染性因素的识别等，被视为联系天然免疫和获得性免疫的桥梁。同时果蝇的Toll信号通路也是不具备获得性免疫的果蝇赖以抵御病毒、细菌和真菌感染，介导天然免疫反应的重要信号通路。 本研究采用大规模EST测序方法，结合Genome Walker库的构建和cDNA末端快速扩增技术，从栉孔扇贝克隆得到CfToll-1、CfMyd88、CfTRAF6和CfCactus这四个Toll样受体信号通路基因的全长cDNA，同时用荧光实时定量PCR技术检测了这些基因的组织分布及在脂多糖（LPS）和肽聚糖（PGN）刺激下的表达规律。 栉孔扇贝Toll样受体（CfToll-1）的cDNA序列全长4308 bp，包含5’非翻译区（UTR）211 bp，3597 bp的开放阅读框，500 bp的3’UTR，最后为18个腺嘌呤的ploy A 尾巴。开放阅读框编码1198个氨基酸的多肽，该多肽的估计分子量为137.41kd，估计的等电点为5.62，该多肽有信号肽，具有一个预测的跨膜区，因此是一种跨膜蛋白。经BLAST比对，CfToll-1基因与节肢动物多种Toll蛋白高度的相似性。SMART（Simple Modular Architecture Research Tool）软件分析，CfToll-1包含典型的Toll样受体的结构：富含亮氨酸的重复序列的胞外区（leucine-rich repeats, LRR），一段跨膜结构域，以及胞内区的TIR结构域（Toll/IL-1 receptor homologous region）。利用Real-time RT-PCR发现CfToll-1mRNA在扇贝体内普遍存在于血细胞、肌肉、外套膜、心、性腺和鳃组织中。利用体外培养的原代血细胞系研究不同浓度LPS刺激后CfToll-1的表达变化，结果显示低剂量（100ng.mL-1 ）LPS 使CfToll-1 mRNA表达量减小，该变化在1.5h、3h 和9h组差异显著，虽然在6h组表达量稍有恢复，但尚未达到对照水平；用1μg.mL-1LPS处理细胞时， 6h组CfToll-1表达量明显上调，约为对照水平的2倍。证实细菌结构脂多糖对CfToll-1基因的表达有影响，且这种影响有剂量依赖效应。 栉孔扇贝Myd88同源基因（CfMyd88）的cDNA序列全长1554bp，包含5’UTR 427 bp，1101bp的开放阅读框，最后为18个腺嘌呤的ploy A 尾。CfMyd88的开放阅读框可编码367个氨基酸的多肽，该多肽的估计分子量为42.37kD，估计的等电点为5.71。利用SMART程序分析发现CfMyd88编码了Death和TIR结构域, 这两个结构域是Myd88特征结构。BLAST程序发现扇贝的序列与数据库哺乳动物的Myd88基因高度同源。原代培养的扇贝血细胞在受到PGN刺激后，CfMyd88 mRNA表达在1.5小时开始下调，直到9小时下调至对照表达量的1/10，证实肽聚糖结构对CfMyd88基因的表达有影响。 栉孔扇贝TRAF6同源基因（CfTRAF6）的cDNA序列全长2510bp，包含5’UTR 337 bp，1965bp的开放阅读框，3’UTR 208bp，最后为21 个腺嘌呤的ploy A 尾巴。CfTRAF6开放阅读框编码655个氨基酸的多肽，该多肽的估计分子量为74.09kD，估计的等电点为6.01。InterPro Scan在线分析发现CfTRAF6有典型的TRAF蛋白家族的特征结构，包括的一个指环结构，两个锌指结构，一个MATH （the meprin and TRAF homology）结构域以及Coiled-coil区域。CfTRAF6的序列与数据库多物种的TRAF6高度同源，同源性最高的是乌贼序列（Identity＝68）和鼠类（Identity＝45%）。利用Real-time RT-PCR，发现CfTRAF6在各组织普遍存在，在性腺中的表达最高。原代培养的扇贝血细胞在受到不同浓度PGN刺激后，与CfMyd88的情况一样，CfTRAF6的表达量变化减少，且这种变化随剂量的增加更加明显。 栉孔扇贝Cactus同源基因（CfCactus）的cDNA序列全长2488bp，包含5’UTR 181 bp，840bp的开放阅读框， 3’UTR 1467bp，最后为19个腺嘌呤的ploy A 尾巴。CfCactus的开放阅读框编码279个氨基酸的多肽，该多肽的估计分子量为31.37 kD；估计的等电点为4.74，与果蝇的Cactus基因的等电点相近（4.5）。利用SMART程序分析发现CfCactus主要编码了ANK结构域（ankyrin repeats）。Cactus基因为哺乳动物NF-κB抑制蛋白IκB的同源分子，BLAST 程序发现扇贝的序列与数据库多物种的Cactus或IκB基因高度同源。同源性最高的是太平洋牡蛎（Identity=35%）和圆尾鲎（Identities = 44%）。对CfTCactus mRNA在扇贝的血细胞、性腺、 肠的组织表达进行分析，并同时与CfTRAF6和CfMyd88的表达量进行了对比，发现CfCactus的表达水平明显高于这两个基因，而且CfTRAF6的基因表达量也高于CfMyd88，表现出级联放大效应。正常情况下，三个基因在性腺的表达量最高，推测这条通路可能和发育等功能密切相关。 通过本研究我们首次在双壳类软体动物找得到与果蝇Toll蛋白家族高度同源的CfToll-1基因，同时发现其他三个在Toll样受体信号传递过程中起重要作用的基因，其中包括在软体动物中获得的第一个Toll样受体的接头分子－CfMyd88基因，该结果直接证明软体动物具有与哺乳动物和节肢动物高度类似Myd88依赖的Toll样受体信号通路。同时通过这些基因组织分布的研究以及细菌结构LPS和PGN对这条通路上基因表达的影响，证明扇贝Toll信号通路可能与在果蝇中一样，参与扇贝的发育和免疫防御等多种功能。

治疗慢性肾功能衰竭的海洋复方新药初步研究

本论文在FPS研究的基础上，结合中医配伍理论，研究将FPS与几味传统中药－大黄、黄芪、泽泻、益母草的提取物组合成治疗慢性肾功能衰竭的海洋复方新药物。由于FPS研究相对成熟，故对复方药物中FPS外其它组分（以下简称复方）的提取、分离工艺以及制定复方质量的标准和检测方法等药学内容进行研究，为下一步新药的开发打下基础。 1. 对复方的醇提与水提进行了比较，确定了复方最佳提取方法－醇提。采用正交实验设计方法对醇提工艺进行优化，以复方中主要有效成分的含量为指标进行综合评价，得到了复方提取的最佳工艺：8倍量95％乙醇回流提取两次，1.5h/次，并对该提取工艺进行了验证实验，结果表明本工艺提取物中各主要有效成分的含量均较高，是可靠可行的。 2. 采用微波水提法，对复方中的单味药－黄芪的主要有效成分黄芪皂苷的提取进行了研究，通过正交实验设计方法优选出了最佳提取工艺为20倍量水、微波功率800 W、对60目黄芪提取两次、15 min/次。将该工艺与传统乙醇回流提取方法进行了对比，结果表明该工艺快速、经济、有较好的皂苷提取率，是黄芪皂苷提取的很好的方法。 3. 进行缺FPS的褐藻糖含量测定阴性对照实验，结果阴性无干扰，褐藻糖含量测定可以作为控制复方质量的一个指标。分别做缺大黄和缺黄芪阴性对照实验，结果总蒽醌和总皂苷含量测定阴性干扰较大，大黄素含量测定阴性无干扰，确定大黄素含量测定为控制复方质量的另一指标。 4. 进行复方提取物质量控制指标之一－大黄素含量测定的分析方法学研究，找到了一稳定可行的方法－HPLC方法，该方法测定条件为：流动相甲醇与0.1%磷酸比例为85：15，柱温40℃，通过ODS柱分离，用二极管阵列检测器在436 nm下测定含量。该方法测定复方提取物中大黄素含量精密度高、专一性好、干扰小，可用来控制复方的质量。

南海北部陆缘深水区构造演化及其资源效应

南海北部陆缘深水区（水深>300m）蕴藏着丰富的资源，我国对深水区的地质研究刚刚起步，但相关领域已成为科研热点。深水油气盆地的构造演化是油气勘探中最重要的基础性研究之一，因此针对我国南海北部陆缘深水区开展构造演化及其资源效应的研究具有重要的理论意义和实际意义。 本文利用钻井和地震资料并结合区域地质资料，重点研究了珠江口盆地深水区的结构和构造演化，取得如下创新性成果：1）首次利用半地堑分析方法系统解剖了研究区的结构、各构造单元发育特征，在此基础上指出五个有利油气运聚带；2）采用回剥法并利用最新资料进行校正，得到了研究区更为可靠的构造沉降曲线，重新划分了裂陷期和裂后期的分界，认为32Ma南海海底扩张之后裂陷作用仍在持续，直到23Ma左右才开始大规模裂后热沉降，并进一步解释了裂陷期延迟的形成机制；3）应用非连续拉张模型计算拉张系数的方程计算了研究区的壳幔拉张系数，指出了深水区地幔相对于地壳的优势伸展作用；首次运用平衡剖面技术重建了研究区的构造发育史，计算了各构造期的拉张率和沉积速率，指出研究区新生代整体呈现持续拉张，拉张系数在1.1-1.24之间；4）精细刻画了水合物钻采区的地质构造特征，建立了该区天然气水合物成藏的概念模式；建立了一套根据地震叠加速度计算流体势的方法，为水合物成藏规律的研究提供了新的思路。

论无心菜属的地理分布

全世界无心菜属植物有306种,隶属10亚属24组,主要分布于欧、亚、美三洲和北非,基本上是北温带分布属。文章分析了亚属的系统位置及其分布式样。地中海区到西亚亚区和中亚亚区的西北部是其分布区中心,也可能是它的起源地,中国横断山脉到青藏高原是其次生分布中心。起源时间至少应该追溯到白垩纪中期。最后,讨论了它的散布途径和现代分布式样的形成及其原因。

Analysis of carbohydrates in a tibetan medicine using new labeling reagent, 1-(2-naphthyl)-3-methyl-5-pyrazolone, by HPLC with DAD detection and ESI-MS identification

A new labeling reagent, 1-(2-naphthyl)-3-methyl-5-pyrazolone (NMP), coupling with liquid chromatography (LC) with electrospray ionization mass spectrometry (ESI-MS) for the detection of carbohydrates from a famous Tibetan medicine is reported. Carbohydrates were derivatized to their bis-NMP-labeled derivatives. The method, in conjunction with a gradient elution, offered a baseline resolution of carbohydrate derivatives on a reversed phase Hypersil ODS-2 column. The carbohydrates such as mannose, galacturonic acid, glucuronic acid, rhamnose, glucose, galactose, xylose, arabinose, and fucose could be successfully detected by UV and ESI-MS. Derivatives showed intense protonated molecular ion at m/z [M+H]+ in positive ion mode. The mass to charge ratios of characteristic fragment ions at m/z 473.0 could be used for the accurately qualitative identification of carbohydrates; this characteristic fragment ion was from the cleavage of C2-C3 bond in the carbohydrate chain giving the specific fragment ions at m/z [MH-CmH2m+1Om-H2O](+) for pentose, hexose, and glyceraldehydes, and at m/z [MH-CmH2m-1Om+1-H2O](+) for alduronic acids, such as galacturonic acid and glucuronic acid (m=n-2, n is carbon atom number of carbohydrate). Compared with the traditional 1-phenyl-3-methyl-5-pyrazolone (PMP) reagent, currently synthesized NMP show the advantage of higher sensitivity to carbohydrate compounds with UV and ESI-MS detection.

地震数据波动方程反演方法研究

Geophysical inversion is a theory that transforms the observation data into corresponding geophysical models. The goal of seismic inversion is not only wave velocity models, but also the fine structures and dynamic process of interior of the earth, expanding to more parameters such as density, aeolotropism, viscosity and so on. As is known to all, Inversion theory is divided to linear and non-linear inversion theories. In rencent 40 years linear inversion theory has formed into a complete and systematic theory and found extensive applications in practice. While there are still many urgent problems to be solved in non-linear inversion theory and practice. Based on wave equation, this dissertation has been mainly involved in the theoretical research of several non-linear inversion methods: waveform inversion, traveltime inversion and the joint inversion about two methods. The objective of gradient waveform inversion is to find a geologic model, thus synthetic seismograms generated by this geologic model are best fitted to observed seismograms. Contrasting with other inverse methods, waveform inversion uses all characteristics of waveform and has high resolution capacity. But waveform inversion is an interface by interface method. An artificial parameter limit should be provided in each inversion iteration. In addition, waveform information will tend to get stuck in local minima if the starting model is too far from the actual model. Based on velocity scanning in traditional seismic data processing, a layer-by-layer waveform inversion method is developed in this dissertation to deal with weaknesses of waveform inversion. Wave equation is used to calculate the traveltime and derivative (perturbation of traveltime with respect to velocity) in wave-equation traveltime inversion (WT). Unlike traditional ray-based travetime inversion, WT has many advantages. No ray tracing or traveltime picking and no high frequency assumption is necessary and good result can be got while starting model is far from real model. But, comparing with waveform inversion, WT has low resolution. Waveform inversion and WT have complementary advantages and similar algorithm, which proves that the joint inversion is a better inversion method. And another key point which this dissertation emphasizes is how to give fullest play to their complementary advantages on the premise of no increase of storage spaces and amount of calculation. Numerical tests are implemented to prove the feasibility of inversion methods mentioned above in this dissertation. Especially for gradient waveform inversion, field data are inversed. This field data are acquired by our group in Wali park and Shunyi district. Real data processing shows there are many problems for waveform inversion to deal with real data. The matching of synthetic seismograms with observed seismograms and noise cancellation are two primary problems. In conclusion, on the foundation of the former experiences, this dissertation has implemented waveform inversions on the basis of acoustic wave equation and elastic wave equation, traveltime inversion on the basis of acoustic wave equation and traditional combined waveform traveltime inversion. Besides the traditional analysis of inversion theory, there are two innovations: layer by layer inversion of seimic reflection data inversion and rapid method for acoustic wave-equation joint inversion.

子洲—清涧地区上古生界储层综合研究

The exploration and study in recent years shows that the upper Paleozoic in the east of Ordos Basin possesses major exploration potential, so it is necessary to have a comprehensive and synthetic research in this area. Following the guideline of T.A. Cross’s high resolution sequences stratigraphy and combined with sedimentology, the strata and sequence in the research area are divided and correlated. This paper emphasizes on the reservoir in this area and its major fruits are: Firstly, form the framework of the high sequence stratigraphy through mainly studying on the data of core, well drilling and field section combining. Then, think that the best reservoir formation mainly appears in the middle or lower part of long arising semi-cycle, and focus on A type and C1 middle sequence cycle that contributes to the development of formation. Next, think the sedimentary source mainly comes from the epimetamorphic crystalline basement in the north of the Ordoes Basin through analyzing depositional background, researching on sandstone petrography, distribution characteristics of the sedimentary system as well as researching on heavy mineral combination characteristics. Fourthly, give priority to Zizhou-Qingjian area for the first time and gain seven lithofacies paleography maps in the No.2 member of Shanxi and the No.8 member of Shihezi through using the method of isochronal lithofacies paleogeography mapping, then bring forth that Sh2 is mainly developed a type I sequence under the margin of ramp lake-basin background. Fifthly, through researching on the characteristics of reservoir petrography and diagenesis, think that all researched areas experienced compaction and cementation, and there is different types of rocks, only little of the primary pores that are made up of litharenite and lithoclastic quartz sandstone is left, while in lithoclastic quartz sandstone, there are still many primary pores Sixthly, through studying on pore types, microstructure, as well as physical property on the key formation, think that the researched area mostly appears typical low pore, low porosity and permeability, which mainly result from sedimentary and diagenesis. Lastly, through researching on classified evaluation in the key formation, productivity analysis, and combing with reservoir distribution, the researched area is divided into three parts, and think that exploration should be emphasized on formation I and II. The characteristics of sandstones distribution in Sh23 member, gas formation distribution and open flow capacity of exploitation well are all consistent properly with the results of reservoir comprehensive evaluation in this thesis proved by the gas production development in 2006.

Recomendação da laranja Aquiri e técnicas para o plantio no Estado do Acre.

O Estado do Acre apresenta boas condições edafoclimáticas para a exploração citrícola, entretanto, a inexistência de informações a respeito do comportamento de cultivares, o uso generalizado do porta-enxerto limão 'Cravo', susceptível ao declínio e a comercialização de mudas oriundas de outras regiões do país, de baixa qualidade, constituem fatores limitantes para o desenvolvimento da citricultura. Preocupada com esses problemas, a Embrapa Acre vem executando pesquisas, desde 1989, com o objetivo de selecionar cultivares de citros e porta-enxertos, adaptados às condições edafoclimáticas de Rio Branco-Acre.

Exploitation of Ebola Virus VP35 Protein to identify new drugs counteracting its type I IFN antagonism

Ebolaviruses (EBOVs) are among the most virulent and deadly pathogens ever known, causing fulminant haemorrhagic fevers in humans and non-human primates. The 2014 outbreak of Ebola virus disease (EVD) in West Africa has claimed more lives than all previous EVD outbreaks combined. The EBOV high mortality rates have been related to the virus-induced impairment of the host innate immunity reaction due to two virus-coded proteins, VP24 and VP35. EBOV VP35 is a multifunctional protein, it is essential for viral replication as a component of the viral RNA polymerase and it also participates in nucleocapsid assembly. Early during EBOV infection, alpha-beta interferon (IFN-α/β) production would be triggered upon recognition of viral dsRNA products by cytoplasmic retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). However, this recognition is efficiently prevented by the double-stranded RNA (dsRNA) binding activity of the EBOV VP35 protein, which hides RLRs binding sites on the dsRNA phosphate backbone as well the 5’-triphosphate (5’-ppp) dsRNA ends to RIG-I recognition. In addition to dsRNA binding and sequestration, EBOV VP35 inhibits IFN-α/β production preventing the activation of the IFN regulatory factor 3 (IRF-3) by direct interaction with cellular proteins. Previous studies demonstrated that single amino acid changes in the VP35 dsRNA binding domain reduce EBOV virulence, indicating that VP35 is an attractive target for antiviral drugs development. Within this context, here we report the establishment of a novel method to characterize the EBOV VP35 inhibitory function of the dsRNA-dependent RIG-I-mediated IFN-β signaling pathway in a BLS2 cell culture setting. In such system, a plasmid containing the promoter region of IFN-β gene linked with a luciferase reporter gene was transfected, together with a EBOV VP35 mammalian expression plasmid, into the IFN-sensitive A549 cell line, and the IFN-induction was stimulated through dsRNA transfection. Through alanine scanning mutational studies with biochemical, cellular and computational methods we highlighted the importance of some VP35 residues involved in dsRNA end-capping binding, such as R312, K282 and R322, that may serve as target for the development of small-molecule inhibitors against EBOV. Furthermore, we identified a synthetic compound that increased IFN-induction only under antiviral response stimulation and subverted VP35 inhibition, proving to be very attractive for the development of an antiviral drug. In conclusion, our results provide the establishment of a new assay as a straightforward tool for the screening of antiviral compounds that target i) dsRNA-VP35 or cellular protein-VP35 interaction and ii) dsRNA-dependent RIG-I-mediated IFN signaling pathway, in order to potentiate the IFN response against VP35 inhibition, setting the bases for further drug development.

La Dolce Morte: Vernacular Cinema and the Itallian Giallo Film

Koven, M. (2006). La Dolce Morte: Vernacular Cinema and the Itallian Giallo Film. Lanham: Scarecrow Press. RAE2008

Welsh Walter of Henley

Falileyev, A. (Ed.). (2006). Welsh Walter of Henley. Mediaeval and Modern Welsh series, 12. Dublin: School of Celtic Studies, Dublin Institute for Advanced Studies. RAE2008

Identifying vibrations that destabilize crystals and characterize the glassy state

Greaves, George; Meneau, F.; Majerus, O.; Jones, D.G., (2005) 'Identifying vibrations that destabilize crystals and characterize the glassy state', Science 308(5726) pp.1299-1302 RAE2008

Plasma acceleration above Martian magnetic anomalies

Grande, Manuel, et al., 'Plasma acceleration above Martian magnetic anomalies', Science (2006) 311(5763) pp.980-983 RAE2008

Hybridization between Brassica napus and B-rapa on a national scale in the United Kingdom

Mike J. Wilkinson, Luisa J. Elliott, Jo?l Allainguillaume, Michael W. Shaw, Carol Norris, Ruth Welters, Matthew Alexander, Jeremy Sweet, David C. Mason (2003). Hybridization between Brassica napus and B-rapa on a national scale in the United Kingdom, Science, 302 (5644), 457-459. RAE2008