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211.
Messenger RNA regulation is a critical mode of controlling gene expression. Regulation of mRNA stability and translation is linked to controls of poly(A) tail length. Poly(A) lengthening can stabilize and translationally activate mRNAs, whereas poly(A) removal can trigger degradation and translational repression. Germline granules (for example, polar granules in flies, P granules in worms) are ribonucleoprotein particles implicated in translational control. Here we report that the Caenorhabditis elegans gene gld-2, a regulator of mitosis/meiosis decision and other germline events, encodes the catalytic moiety of a cytoplasmic poly(A) polymerase (PAP) that is associated with P granules in early embryos. Importantly, the GLD-2 protein sequence has diverged substantially from that of conventional eukaryotic PAPs, and lacks a recognizable RRM (RNA recognition motif)-like domain. GLD-2 has little PAP activity on its own, but is stimulated in vitro by GLD-3. GLD-3 is also a developmental regulator, and belongs to the Bicaudal-C family of RNA binding proteins. We suggest that GLD-2 is the prototype for a class of regulatory cytoplasmic PAPs that are recruited to specific mRNAs by a binding partner, thereby targeting those mRNAs for polyadenylation and increased expression. 相似文献
212.
Elisabeth K SHAGHAGHI WU Yue Alain M GARDIER Christian JACQUOT Marc PALLARDY 《石河子大学学报(自然科学版)》2004,22(1):11-19
在F344雄性大鼠腹腔注射血蓝蛋白(KLH),研究T 细胞依赖抗原初始免疫反应对中枢神经系统5 羟色胺(5 HT)代谢的影响。当免疫刺激大鼠4天后,其下丘脑匀浆5 羟色胺水平出现降低,同时应用在体脑微透析技术研究发现清醒大鼠腹腔注射血蓝蛋白4天后,其下丘脑前叶细胞外液的5 羟色胺水平增加。为了评价在免疫反应中大鼠下丘脑5 羟色胺释放效应,本文应用氯苯丙胺(PCA)选择性预先耗竭5 羟色胺释放,并测定这些动物在注射血蓝蛋白后抗体产生情况。结果显示在应用氯苯丙胺预处理的血蓝蛋白免疫动物特异抗体IgM和IgG与未用氯苯丙胺预处理的动物比较均有明显增加(P<0.01)。上述资料表明,对于T 细胞依赖抗原,其初始抗体产生的量是由位于下丘脑5 羟色胺神经终端抑制性递质释放所调节。 相似文献
213.
214.
Janecke AR Thompson DA Utermann G Becker C Hübner CA Schmid E McHenry CL Nair AR Rüschendorf F Heckenlively J Wissinger B Nürnberg P Gal A 《Nature genetics》2004,36(8):850-854
We identified three consanguineous Austrian kindreds with 15 members affected by autosomal recessive childhood-onset severe retinal dystrophy, a genetically heterogeneous group of disorders characterized by degeneration of the photoreceptor cells. A whole-genome scan by microarray analysis of single-nucleotide polymorphisms (ref. 2) identified a founder haplotype and defined a critical interval of 1.53 cM on chromosome 14q23.3-q24.1 that contains the gene associated with this form of retinal dystrophy. RDH12 maps in this region and encodes a retinol dehydrogenase proposed to function in the visual cycle. A homozygous 677A-->G transition (resulting in Y226C) in RDH12 was present in all affected family members studied, as well as in two Austrian individuals with sporadic retinal dystrophy. We identified additional mutations in RDH12 in 3 of 89 non-Austrian individuals with retinal dystrophy: a 5-nucleotide deletion (806delCCCTG) and the transition 565C-->T (resulting in Q189X), each in the homozygous state, and 146C-->T (resulting in T49M) and 184C-->T (resulting in R62X) in compound heterozygosity. When expressed in COS-7 cells, Cys226 and Met49 variants had diminished and aberrant activity, respectively, in interconverting isomers of retinol and retinal. The severe visual impairment of individuals with mutations in RDH12 is in marked contrast to the mild visual deficiency in individuals with fundus albipunctatus caused by mutations in RDH5, encoding another retinal dehydrogenase. Our studies show that RDH12 is associated with retinal dystrophy and encodes an enzyme with a unique, nonredundant role in the photoreceptor cells. 相似文献
215.
Vennerstrom JL Arbe-Barnes S Brun R Charman SA Chiu FC Chollet J Dong Y Dorn A Hunziker D Matile H McIntosh K Padmanilayam M Santo Tomas J Scheurer C Scorneaux B Tang Y Urwyler H Wittlin S Charman WN 《Nature》2004,430(7002):900-904
The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which--the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)--may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project. 相似文献
216.
Experimental evidence for the existence of iron-rich metal in the Earth's lower mantle 总被引:1,自引:0,他引:1
The oxidation state recorded by rocks from the Earth's upper mantle can be calculated from measurements of the distribution of Fe3+ and Fe2+ between the constituent minerals. The capacity for minerals to incorporate Fe3+ may also be a significant factor controlling the oxidation state of the mantle, and high-pressure experimental measurements of this property might provide important insights into the redox state of the more inaccessible deeper mantle. Here we show experimentally that the Fe3+ content of aluminous silicate perovskite, the dominant lower-mantle mineral, is independent of oxygen fugacity. High levels of Fe3+ are present in perovskite even when it is in chemical equilibrium with metallic iron. Silicate perovskite in the lower mantle will, therefore, have an Fe3+/total Fe ratio of at least 0.6, resulting in a whole-rock ratio of over ten times that of the upper mantle. Consequently, the lower mantle must either be enriched in Fe3+ or Fe3+ must form by the disproportionation of Fe2+ to produce Fe3+ plus iron metal. We argue that the lower mantle contains approximately 1 wt% of a metallic iron-rich alloy. The mantle's oxidation state and siderophile element budget have probably been influenced by the presence of this alloy. 相似文献
217.
218.
Sawaya MR Sambashivan S Nelson R Ivanova MI Sievers SA Apostol MI Thompson MJ Balbirnie M Wiltzius JJ McFarlane HT Madsen AØ Riekel C Eisenberg D 《Nature》2007,447(7143):453-457
Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-beta spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of beta-sheets, with the facing side chains of the two sheets interdigitated in a dry 'steric zipper'. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer's amyloid-beta and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, alpha-synuclein and beta(2)-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains. 相似文献
219.
220.
Methylation of histone H3R2 by PRMT6 and H3K4 by an MLL complex are mutually exclusive 总被引:1,自引:0,他引:1
Guccione E Bassi C Casadio F Martinato F Cesaroni M Schuchlautz H Lüscher B Amati B 《Nature》2007,449(7164):933-937