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The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified, the functional role of MDA5 and the relationship between these dsRNA detectors in vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5-/-) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5-/- mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.  相似文献   
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Shugoshin collaborates with protein phosphatase 2A to protect cohesin   总被引:1,自引:0,他引:1  
Sister chromatid cohesion, mediated by a complex called cohesin, is crucial--particularly at centromeres--for proper chromosome segregation in mitosis and meiosis. In animal mitotic cells, phosphorylation of cohesin promotes its dissociation from chromosomes, but centromeric cohesin is protected by shugoshin until kinetochores are properly captured by the spindle microtubules. However, the mechanism of shugoshin-dependent protection of cohesin is unknown. Here we find a specific subtype of serine/threonine protein phosphatase 2A (PP2A) associating with human shugoshin. PP2A colocalizes with shugoshin at centromeres and is required for centromeric protection. Purified shugoshin complex has an ability to reverse the phosphorylation of cohesin in vitro, suggesting that dephosphorylation of cohesin is the mechanism of protection at centromeres. Meiotic shugoshin of fission yeast also associates with PP2A, with both proteins collaboratively protecting Rec8-containing cohesin at centromeres. Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis.  相似文献   
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Haploinsufficiency of NSD1 causes Sotos syndrome   总被引:14,自引:0,他引:14  
We isolated NSD1 from the 5q35 breakpoint in an individual with Sotos syndrome harboring a chromosomal translocation. We identified 1 nonsense, 3 frameshift and 20 submicroscopic deletion mutations of NSD1 among 42 individuals with sporadic cases of Sotos syndrome. The results indicate that haploinsufficiency of NSD1 is the major cause of Sotos syndrome.  相似文献   
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This paper describes the latest version of the Chinese-Japanese-English handheld speech-tospeech translation system developed by NICT/ATR, which is now ready to be deployed for travelers. With the entire speech-to-speech translation function being implemented into one terminal, it realizes real-time, location-free speech-to-speech translation. A new noise-suppression technique notably improves the speech recognition performance. Corpus-based approaches of speech recognition, machine translation, and speech synthesis enable coverage of a wide variety of topics and portability to other languages. Test results show that the character accuracy of speech recognition is 82%-94% for Chinese speech, with a bilingual evaluation understudy score of machine translation is 0.55-0.74 for Chinese-Japanese and Chinese-English  相似文献   
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The medaka draft genome and insights into vertebrate genome evolution   总被引:3,自引:0,他引:3  
Teleosts comprise more than half of all vertebrate species and have adapted to a variety of marine and freshwater habitats. Their genome evolution and diversification are important subjects for the understanding of vertebrate evolution. Although draft genome sequences of two pufferfishes have been published, analysis of more fish genomes is desirable. Here we report a high-quality draft genome sequence of a small egg-laying freshwater teleost, medaka (Oryzias latipes). Medaka is native to East Asia and an excellent model system for a wide range of biology, including ecotoxicology, carcinogenesis, sex determination and developmental genetics. In the assembled medaka genome (700 megabases), which is less than half of the zebrafish genome, we predicted 20,141 genes, including approximately 2,900 new genes, using 5'-end serial analysis of gene expression tag information. We found single nucleotide polymorphisms (SNPs) at an average rate of 3.42% between the two inbred strains derived from two regional populations; this is the highest SNP rate seen in any vertebrate species. Analyses based on the dense SNP information show a strict genetic separation of 4 million years (Myr) between the two populations, and suggest that differential selective pressures acted on specific gene categories. Four-way comparisons with the human, pufferfish (Tetraodon), zebrafish and medaka genomes revealed that eight major interchromosomal rearrangements took place in a remarkably short period of approximately 50 Myr after the whole-genome duplication event in the teleost ancestor and afterwards, intriguingly, the medaka genome preserved its ancestral karyotype for more than 300 Myr.  相似文献   
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实验研究发现,喷氨脱硝过程中是否会产生大量的N_2O,在很大程度上取决于喷氨处的烟气的成分,氧化性气氛有利于N_2O的产生.对喷氨脱硝的均相化学反应过程进行的动力学模拟表明,在混合良好的还原性烟气中喷入氨气不会导致N_2O排放量大幅度增加,但如果喷入的氨气与烟气和空气混合不良,或者烟气中存在由NH_3转化的氰基成分,那么N_2O的排放量会有所增加.  相似文献   
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A non‐linear dynamic model is introduced for multiplicative seasonal time series that follows and extends the X‐11 paradigm where the observed time series is a product of trend, seasonal and irregular factors. A selection of standard seasonal and trend component models used in additive dynamic time series models are adapted for the multiplicative framework and a non‐linear filtering procedure is proposed. The results are illustrated and compared to X‐11 and log‐additive models using real data. In particular it is shown that the new procedures do not suffer from the trend bias present in log‐additive models. Copyright © 2002 John Wiley & Sons, Ltd.  相似文献   
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