排序方式: 共有33条查询结果,搜索用时 15 毫秒
21.
Caudy AA Ketting RF Hammond SM Denli AM Bathoorn AM Tops BB Silva JM Myers MM Hannon GJ Plasterk RH 《Nature》2003,425(6956):411-414
RNA interference (RNAi) regulates gene expression by the cleavage of messenger RNA, by mRNA degradation and by preventing protein synthesis. These effects are mediated by a ribonucleoprotein complex known as RISC (RNA-induced silencing complex). We have previously identified four Drosophila components (short interfering RNAs, Argonaute 2 (ref. 2), VIG and FXR) of a RISC enzyme that degrades specific mRNAs in response to a double-stranded-RNA trigger. Here we show that Tudor-SN (tudor staphylococcal nuclease)--a protein containing five staphylococcal/micrococcal nuclease domains and a tudor domain--is a component of the RISC enzyme in Caenorhabditis elegans, Drosophila and mammals. Although Tudor-SN contains non-canonical active-site sequences, we show that purified Tudor-SN exhibits nuclease activity similar to that of other staphylococcal nucleases. Notably, both purified Tudor-SN and RISC are inhibited by a specific competitive inhibitor of micrococcal nuclease. Tudor-SN is the first RISC subunit to be identified that contains a recognizable nuclease domain, and could therefore contribute to the RNA degradation observed in RNAi. 相似文献
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The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystin 总被引:11,自引:0,他引:11
Mollet G Salomon R Gribouval O Silbermann F Bacq D Landthaler G Milford D Nayir A Rizzoni G Antignac C Saunier S 《Nature genetics》2002,32(2):300-305
Nephronophthisis, the most common genetic cause of chronic renal failure in children, is a progressive tubulo-interstitial kidney disorder that is inherited as an autosomal recessive trait. The disease is characterized by polyuria, growth retardation and deterioration of renal function during childhood or adolescence. The most prominent histological features are modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Nephronophthisis can also be associated with conditions affecting extrarenal organs, such as retinitis pigmentosa (Senior-L?ken syndrome) and ocular motor apraxia (Cogan syndrome). Three loci are associated with the juvenile, infantile and adolescent forms, on chromosomes 2q13 (NPHP1; refs 5,6), 9q22 (NPHP2; ref. 7) and 3q21 (NPHP3; ref. 8), respectively. NPHP1, the only gene identified so far, encodes nephrocystin, which contains a Src homology 3 (SH3) domain and interacts with intracytoplasmic proteins involved in cell adhesion. Recently, a second locus associated with the juvenile form of the disease, NPHP4, was mapped to chromosome 1p36 (ref. 14). We carried out haplotype analysis of families affected with nephronophthisis that were not linked to the NPHP1, NPHP2 or NPHP3 loci, using markers covering this region. This allowed us to reduce the NPHP4 interval to a one centimorgan interval between D1S2795 and D1S2870, which contains six genes. We identified five different mutations in one of these genes, designated NPHP4, in unrelated individuals with nephronophthisis. The NPHP4 gene encodes a 1,250-amino acid protein of unknown function that we named nephrocystin-4. We demonstrated the interaction of nephrocystin-4 with nephrocystin suggesting that these two proteins participate in a common signaling pathway. 相似文献
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Abdullah Aslan Ayd?n Güne? Emin Salur mer Sinan ahin Hakan Burak Karada Ahmet Akdemir 《矿物冶金与材料学报》2018,25(9):1070-1079
In this study, the processing and mechanical properties of porous metal matrix composites (MMCs) composed of spheroidal cast iron chips (GGG40) and bronze chips (CuSn10) and formed by hot isostatic pressing were investigated. Bronze chips (CuSn10) were used as a matrix component, and spheroidal cast iron (GGG40) chips were used as a reinforcement component. The MMCs were produced with different CuSn10 contents (90wt%, 80wt%, 70wt%, and 60wt%). The hot isostatic pressing process was performed under three different pressures and temperatures. The produced MMCs were characterized using density tests, Brinell hardness tests, and compression tests. In addition, the consolidation mechanism was investigated by X-ray diffraction (XRD) analysis and scanning electron microscopy. The test results were compared with those for bulk CuSn10 and bulk GGG40. Mechanical tests results revealed that the metallic chips can be recycled by using hot pressing and that the mechanical properties of the produced MMCs were similar to those of bulk CuSn10. XRD and microscopy studies showed that no intermetallic compounds formed between the metallic chips. The results showed that the CuSn10 and GGG40 chips were consolidated by mechanical interlocking. 相似文献
24.
Ambra1 regulates autophagy and development of the nervous system 总被引:1,自引:0,他引:1
Fimia GM Stoykova A Romagnoli A Giunta L Di Bartolomeo S Nardacci R Corazzari M Fuoco C Ucar A Schwartz P Gruss P Piacentini M Chowdhury K Cecconi F 《Nature》2007,447(7148):1121-1125
Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals. 相似文献
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Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule 总被引:10,自引:0,他引:10
Lalioti MD Zhang J Volkman HM Kahle KT Hoffmann KE Toka HR Nelson-Williams C Ellison DH Flavell R Booth CJ Lu Y Geller DS Lifton RP 《Nature genetics》2006,38(10):1124-1132
The mechanisms that govern homeostasis of complex systems have been elusive but can be illuminated by mutations that disrupt system behavior. Mutations in the gene encoding the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a syndrome featuring hypertension and hyperkalemia. We show that physiology in mice transgenic for genomic segments harboring wild-type (TgWnk4(WT)) or PHAII mutant (TgWnk4(PHAII)) Wnk4 is changed in opposite directions: TgWnk4(PHAII) mice have higher blood pressure, hyperkalemia, hypercalciuria and marked hyperplasia of the distal convoluted tubule (DCT), whereas the opposite is true in TgWnk4(WT) mice. Genetic deficiency for the Na-Cl cotransporter of the DCT (NCC) reverses phenotypes seen in TgWnk4(PHAII) mice, demonstrating that the effects of the PHAII mutation are due to altered NCC activity. These findings establish that Wnk4 is a molecular switch that regulates the balance between NaCl reabsorption and K+ secretion by altering the mass and function of the DCT through its effect on NCC. 相似文献
27.
In the event studies, the accuracy of the abnormal returns assessment is highly dependent on the accuracy of the preceding expected return model. If the expected return model is inadequate, there is a possibility that a part of returns is labeled as abnormal returns even though they are not. Currently, we have a variety of options to set up an expected return model. To obtain unbiased abnormal returns, one should pay attention to the performance of the expected return model. In this research, we propose that the optimal forecast lemma can be consulted beforehand so that minimizing the optimal forecast error in the expected return model will yield unbiased abnormal returns. We introduce and prove a proposition that the optimal forecast error is an unbiased estimator for abnormal return. The proposition induces assessing the performance of abnormal return estimation to preemptively evaluate the out-sample forecast accuracy of the model employed. In an illustrative dataset, we examine various models. The approach requires preliminary computational effort; however, it is useful for accurately obtaining the abnormal return predictions. 相似文献
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Barak T Kwan KY Louvi A Demirbilek V Saygı S Tüysüz B Choi M Boyacı H Doerschner K Zhu Y Kaymakçalan H Yılmaz S Bakırcıoğlu M Cağlayan AO Oztürk AK Yasuno K Brunken WJ Atalar E Yalçınkaya C Dinçer A Bronen RA Mane S Ozçelik T Lifton RP Sestan N Bilgüvar K Günel M 《Nature genetics》2011,43(6):590-594
The biological basis for regional and inter-species differences in cerebral cortical morphology is poorly understood. We focused on consanguineous Turkish families with a single affected member with complex bilateral occipital cortical gyration abnormalities. By using whole-exome sequencing, we initially identified a homozygous 2-bp deletion in LAMC3, the laminin γ3 gene, leading to an immediate premature termination codon. In two other affected individuals with nearly identical phenotypes, we identified a homozygous nonsense mutation and a compound heterozygous mutation. In human but not mouse fetal brain, LAMC3 is enriched in postmitotic cortical plate neurons, localizing primarily to the somatodendritic compartment. LAMC3 expression peaks between late gestation and late infancy, paralleling the expression of molecules that are important in dendritogenesis and synapse formation. The discovery of the molecular basis of this unusual occipital malformation furthers our understanding of the complex biology underlying the formation of cortical gyrations. 相似文献
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Morgan NV Westaway SK Morton JE Gregory A Gissen P Sonek S Cangul H Coryell J Canham N Nardocci N Zorzi G Pasha S Rodriguez D Desguerre I Mubaidin A Bertini E Trembath RC Simonati A Schanen C Johnson CA Levinson B Woods CG Wilmot B Kramer P Gitschier J Maher ER Hayflick SJ 《Nature genetics》2006,38(7):752-754
Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis. 相似文献
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