2'-O methylation of the viral mRNA cap evades host restriction by IFIT family members

Cellular messenger RNA (mRNA) of higher eukaryotes and many viral RNAs are methylated at the N-7 and 2'-O positions of the 5' guanosine cap by specific nuclear and cytoplasmic methyltransferases (MTases), respectively. Whereas N-7 methylation is essential for RNA translation and stability, the function of 2'-O methylation has remained uncertain since its discovery 35 years ago. Here we show that a West Nile virus (WNV) mutant (E218A) that lacks 2'-O MTase activity was attenuated in wild-type primary cells and mice but was pathogenic in the absence of type I interferon (IFN) signalling. 2'-O methylation of viral RNA did not affect IFN induction in WNV-infected fibroblasts but instead modulated the antiviral effects of IFN-induced proteins with tetratricopeptide repeats (IFIT), which are interferon-stimulated genes (ISGs) implicated in regulation of protein translation. Poxvirus and coronavirus mutants that lacked 2'-O MTase activity similarly showed enhanced sensitivity to the antiviral actions of IFN and, specifically, IFIT proteins. Our results demonstrate that the 2'-O methylation of the 5' cap of viral RNA functions to subvert innate host antiviral responses through escape of IFIT-mediated suppression, and suggest an evolutionary explanation for 2'-O methylation of cellular mRNA: to distinguish self from non-self RNA. Differential methylation of cytoplasmic RNA probably serves as an example for pattern recognition and restriction of propagation of foreign viral RNA in host cells.     

Model construction and analyses of a class of scale-free network with variable power law exponent

多数现实网络的度分布指数(幂指数)介于(2,3),而BA网络的度分布指数恒等于3.基于BA模型,引入老节点之间的择优连接机制,建立了一类变幂率的无标度网络模型,给出了这类复杂网络演化的解析结果,证明了在不同的参数下,其幂指数介于[2,3].同时指出,BA网络只是该模型的一个特例,通过一些实际网络数据的分析,说明了该网络模型的有效性和合理性.     

Study on simulation and scheduling algorithm of CAN control for independently driving electric vehicle

Safety-critical applications such as the independently driving systems of electric vehicle (EV) require a high degree of reliability. The controller area network (CAN) is used extensively in the control sectors. A new real-time and reliable scheduling algorithm based on time-triggered scheduler with a focus on the CAN-based distributed control systems for independently driving EV is exploited. A distributed control network model for a dual-wheel independently driving EV is established. The timing and reliability analysis in the worst case with the algorithm is used to evaluate the predictability and dependability and the simulation based on the algorithm with CANoe software is designed. The results indicate the algorithm is more predicable and dependable.     

Study on laser welded heat-affected zone in new ultralow carbon bainitic steel

800 MPa grade ultralow carbon bainitic (NULCB) steel is the recently developed new generation steel, which was produced by thermo mechanical controlled processing & relaxation-precipitation controlling transformation (TMCP&RPC) technique. The microstructure and the mechanical properties of the heat-affected zone (HAZ) in NULCB steel under laser welding conditions were investigated by using a Gleeble-1500 thermal simulator. The experimental results indicate that the simplex microstructure in the HAZ is granular bainite that consists of bainite-ferrite (BF) lath and M-A constituent when the cooling time from 800 to 500℃ (t_8/5) is 0.3-30 s, and the M-A constituent consists of twinned martensite and residual austenite. As t_8/5 increases, the hardness and tensile strength of HAZ decreases, but they are higher than that of the base metal, indicating the absence of softened zone after laser welding. The impact toughness of HAZ increases at first and then decreases when t_8/5 increases. The impact energy of HAZ is much higher than that of the base metal when t_8/5 is between 3 and 15 s. It indicates that excellent low temperature toughness can be obtained under appropriate laser welding conditions.     

Familial hypobetalipoproteinemia: genetics and metabolism

Familial hypobetalipoproteinemia (FHBL), an autosomal dominant disorder, is defined as <5^th percentile LDL-cholesterol or apolipoprotein (apo) B in the plasma. FHBL subjects are generally heterozygous and asymptomatic. Three genetic forms exist: (i) premature stop codon specifying mutations of APOB; (ii) FHBL linked to a susceptibility locus on the chromosome 3p21; and (iii) FHBL linked neither to APOB nor to the chromosome 3p21. In heterozygous apoB-defective FHBL, the hepatic VLDL export system is defective because apoB 100, the product of the normal allele, is produced at ∼25% of normal rate, and truncated apoB is cleared too rapidly. The reduced capacity for hepatic triglyceride export increases hepatic fat three-fold. Indexes of adiposity and insulin action are similar to controls. ‘Knock-in’ mouse models of apoB truncations resemble human FHBL phenotypes. Liver fat in the chromosome 3p21-linked FHBL is normal. Elucidation of the genetic basis of the non-apoB FHBL could uncover attractive targets for lipid-lowering therapy. (See note added in proof.)Received 27 October 2004; received after revision 1 February 2005; accepted 22 February 2005     

A genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway

Members of the Hedgehog (Hh) family of signaling proteins are powerful regulators of developmental processes in many organisms and have been implicated in many human disease states. Here we report the results of a genome-wide RNA interference screen in Drosophila melanogaster cells for new components of the Hh signaling pathway. The screen identified hundreds of potential new regulators of Hh signaling, including many large protein complexes with pleiotropic effects, such as the coat protein complex I (COPI) complex, the ribosome and the proteasome. We identified the multimeric protein phosphatase 2A (PP2A) and two new kinases, the D. melanogaster orthologs of the vertebrate PITSLRE and cyclin-dependent kinase-9 (CDK9) kinases, as Hh regulators. We also identified a large group of constitutive and alternative splicing factors, two nucleoporins involved in mRNA export and several RNA-regulatory proteins as potent regulators of Hh signal transduction, indicating that splicing regulation and mRNA transport have a previously unrecognized role in Hh signaling. Finally, we showed that several of these genes have conserved roles in mammalian Hh signaling.     

Overview of the Alliance for Cellular Signaling

The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells--B lymphocytes (the cells of the immune system) and cardiac myocytes--to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community.     

最优弹道形成制导的分析解

本文介绍一种关于导弹弹道中段和末段的混合制导规律,以提高导弹的射程及其优良的拦截特性。文中导出了中段和末段三维飞行的闭环非线性最优制导规律的解析解。这种混合制导规律在中制导段目标方向发生变化时能迅速修正导弹的弹道。在从中段转到末段时,航向误差可以达到零。这种制导的算法取反馈形式,既可用于惯性坐标系,又可用于寻的坐标系。此算法在弹上实现起来相当简单,已经成功地用于在线工作。     

Postnatal isl1+ cardioblasts enter fully differentiated cardiomyocyte lineages

The purification, renewal and differentiation of native cardiac progenitors would form a mechanistic underpinning for unravelling steps for cardiac cell lineage formation, and their links to forms of congenital and adult cardiac diseases. Until now there has been little evidence for native cardiac precursor cells in the postnatal heart. Herein, we report the identification of isl1+ cardiac progenitors in postnatal rat, mouse and human myocardium. A cardiac mesenchymal feeder layer allows renewal of the isolated progenitor cells with maintenance of their capability to adopt a fully differentiated cardiomyocyte phenotype. Tamoxifen-inducible Cre/lox technology enables selective marking of this progenitor cell population including its progeny, at a defined time, and purification to relative homogeneity. Co-culture studies with neonatal myocytes indicate that isl1+ cells represent authentic, endogenous cardiac progenitors (cardioblasts) that display highly efficient conversion to a mature cardiac phenotype with stable expression of myocytic markers (25%) in the absence of cell fusion, intact Ca2+-cycling, and the generation of action potentials. The discovery of native cardioblasts represents a genetically based system to identify steps in cardiac cell lineage formation and maturation in development and disease.