Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses

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.     

Shugoshin collaborates with protein phosphatase 2A to protect cohesin

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.     

NICT/ATR Chinese-Japanese-English Speech-to-Speech Translation System

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     

Haploinsufficiency of NSD1 causes Sotos syndrome

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.     

Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome

By exome sequencing, we found de novo SMARCB1 mutations in two of five individuals with typical Coffin-Siris syndrome (CSS), a rare autosomal dominant anomaly syndrome. As SMARCB1 encodes a subunit of the SWItch/Sucrose NonFermenting (SWI/SNF) complex, we screened 15 other genes encoding subunits of this complex in 23 individuals with CSS. Twenty affected individuals (87%) each had a germline mutation in one of six SWI/SNF subunit genes, including SMARCB1, SMARCA4, SMARCA2, SMARCE1, ARID1A and ARID1B.     

一类新型多氟氮超酸锂盐电解液的性质研究

合成了一类新型多氟氮超酸锂金属盐──二（多氟烷氧基）磺酰基氨化锂，ＬｉＮ（ＳＯ２ＯＲｆ）２（Ｒｆ＝－ＣＨ２ＣＦ３，－ＣＨ２ＣＦ２ＣＦ３，－ＣＨ３ＣＦ２ＣＦ２Ｈ，－ＣＨ（ＣＦ３）２），并用ＩＲ，１ＨＮＭＲ，１９ＦＮＭＲ对它们的结构进行了表征．以碳酸丙烯酯（ＰＣ）和乙二醇二甲醇（ＤＭＥ）为混合溶剂，研究了由这些锂盐组成的电解液的性质．结果显示，新型氟氮超酸锂盐的电化学性能十分优良，可以满足锂电池电解液的要求．讨论了引入不同的取代基所导致的对溶液导电性和阳极抗氧化性能的影响．     

Periostin in vitreoretinal diseases

Proliferative vitreoretinal diseases such as diabetic retinopathy, proliferative vitreoretinopathy (PVR), and age-related macular degeneration are a leading cause of decreased vision and blindness in developed countries. In these diseases, retinal fibro(vascular) membrane (FVM) formation above and beneath the retina plays an important role. Gene expression profiling of human FVMs revealed significant upregulation of periostin. Subsequent analyses demonstrated increased periostin expression in the vitreous of patients with both proliferative diabetic retinopathy and PVR. Immunohistochemical analysis showed co-localization of periostin with α-SMA and M2 macrophage markers in FVMs. In vitro, periostin blockade inhibited migration and adhesion induced by PVR vitreous and transforming growth factor-β2 (TGF-β2). In vivo, a novel single-stranded RNAi agent targeting periostin showed the inhibitory effect on experimental retinal and choroidal FVM formation without affecting the viability of retinal cells. These results indicated that periostin is a pivotal molecule for FVM formation and a promising therapeutic target for these proliferative vitreoretinal diseases.     

A non‐linear dynamic model for multiplicative seasonal‐trend decomposition

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.     

p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload

Cardiac hypertrophy occurs as an adaptive response to increased workload to maintain cardiac function. However, prolonged cardiac hypertrophy causes heart failure, and its mechanisms are largely unknown. Here we show that cardiac angiogenesis is crucially involved in the adaptive mechanism of cardiac hypertrophy and that p53 accumulation is essential for the transition from cardiac hypertrophy to heart failure. Pressure overload initially promoted vascular growth in the heart by hypoxia-inducible factor-1 (Hif-1)-dependent induction of angiogenic factors, and inhibition of angiogenesis prevented the development of cardiac hypertrophy and induced systolic dysfunction. Sustained pressure overload induced an accumulation of p53 that inhibited Hif-1 activity and thereby impaired cardiac angiogenesis and systolic function. Conversely, promoting cardiac angiogenesis by introducing angiogenic factors or by inhibiting p53 accumulation developed hypertrophy further and restored cardiac dysfunction under chronic pressure overload. These results indicate that the anti-angiogenic property of p53 may have a crucial function in the transition from cardiac hypertrophy to heart failure.