Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA

Innate immune defences are essential for the control of virus infection and are triggered through host recognition of viral macromolecular motifs known as pathogen-associated molecular patterns (PAMPs). Hepatitis C virus (HCV) is an RNA virus that replicates in the liver, and infects 200 million people worldwide. Infection is regulated by hepatic immune defences triggered by the cellular RIG-I helicase. RIG-I binds PAMP RNA and signals interferon regulatory factor 3 activation to induce the expression of interferon-alpha/beta and antiviral/interferon-stimulated genes (ISGs) that limit infection. Here we identify the polyuridine motif of the HCV genome 3' non-translated region and its replication intermediate as the PAMP substrate of RIG-I, and show that this and similar homopolyuridine or homopolyriboadenine motifs present in the genomes of RNA viruses are the chief feature of RIG-I recognition and immune triggering in human and murine cells. 5' terminal triphosphate on the PAMP RNA was necessary but not sufficient for RIG-I binding, which was primarily dependent on homopolymeric ribonucleotide composition, linear structure and length. The HCV PAMP RNA stimulated RIG-I-dependent signalling to induce a hepatic innate immune response in vivo, and triggered interferon and ISG expression to suppress HCV infection in vitro. These results provide a conceptual advance by defining specific homopolymeric RNA motifs within the genome of HCV and other RNA viruses as the PAMP substrate of RIG-I, and demonstrate immunogenic features of the PAMP-RIG-I interaction that could be used as an immune adjuvant for vaccine and immunotherapy approaches.     

Green revolution: a mutant gibberellin-synthesis gene in rice

The chronic food shortage that was feared after the rapid expansion of the world population in the 1960s was averted largely by the development of a high-yielding semi-dwarf variety of rice known as IR8, the so-called rice 'green revolution'. The short stature of IR8 is due to a mutation in the plant's sd1 gene, and here we identify this gene as encoding an oxidase enzyme involved in the biosynthesis of gibberellin, a plant growth hormone. Gibberellin is also implicated in green-revolution varieties of wheat, but the reduced height of those crops is conferred by defects in the hormone's signalling pathway.     

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Stem cells reside in a specialized regulatory microenvironment or niche, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity. The niche may also protect stem cells from environmental insults including cytotoxic chemotherapy and perhaps pathogenic immunity. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche in the bone marrow, a site where immune reactivity exists. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30?days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (T(reg)) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with T(reg) cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. T(reg) cells seem to participate in creating a localized zone where HSPCs reside and where T(reg) cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.     

多层焊焊接应力分布对管子局部热处理应力释放准则的影响

采用有限元方法构造了轴对称模型下多层焊应力分布,用粘弹塑性有限元方法对管子多层焊后不同局部热外理条件下应力分量的分布情况进行了研究.结果表明,管子内、外侧残余应力和加热宽度表现出不同的规律管子外侧的残余应力随加热宽度的增加缓慢下降;管子内侧的残余应力在较小的加热宽度下可以得到有效消除.残余应力与加热宽度关系表现为两种类型一种是理想衰减型;另一种为局部最小型.多层焊形式下的残余应力与加热宽度的关系表现为后一种型式.加热宽度2B=5Rt较为合理.过大的加热宽度时局部热处理应力释放的作用不大.最后,进行了管子的多层焊和局部热处理试验,并采用X-射线法对局部热处理后的应力进行了测量.     

Essential role for Gab2 in the allergic response.

Dos/Gab family scaffolding adapters (Dos, Gab1, Gab2) bind several signal relay molecules, including the protein-tyrosine phosphatase Shp-2 and phosphatidylinositol-3-OH kinase (PI(3)K); they are also implicated in growth factor, cytokine and antigen receptor signal transduction. Mice lacking Gab1 die during embryogenesis and show defective responses to several stimuli. Here we report that Gab2-/- mice are viable and generally healthy; however, the response (for example, degranulation and cytokine gene expression) of Gab2-/- mast cells to stimulation of the high affinity immunoglobulin-epsilon (IgE) receptor Fc(epsilon)RI is defective. Accordingly, allergic reactions such as passive cutaneous and systemic anaphylaxis are markedly impaired in Gab2-/- mice. Biochemical analyses reveal that signalling pathways dependent on PI(3)K, a critical component of Fc(epsilon)RI signalling, are defective in Gab2-/- mast cells. Our data identify Gab2 as the principal activator of PI(3)K in response to Fc(epsilon)RI activation, thereby providing genetic evidence that Dos/Gab family scaffolds regulate the PI(3)K pathway in vivo. Gab2 and/or its associated signalling molecules may be new targets for developing drugs to treat allergy.     

Study of A Multi-criteria Evaluation Methodology for Nuclear Fuel Cycle System Based on Sustainability

1Introduction Thegrowthofworldpopulationandtherapidgrowthofeconomicactivityhavecausedthe worldwideconcernsontheissuesofenergyshortageandglobalclimatechange.Sincethe energyconsumptionhassomewhatrelationshipwiththeglobalclimatechangeandtheemergence ofanti nuclearprotest,theenergyissueshavebecomepoliticalandpublicissues.Therelated stakeholderswithdifferentinterestsandpreferencesbegantocaretheassessmentforvariousenergysystems.Theevaluationforenergy systemhasalsochangedfrommonetaryevaluation,suchas…     

Specific reaction of aloe extract with serum proteins of various animals.

We found that aloe extract contains a lectin-like substance which reacts with serum proteins of various animals. Furthermore, in human serum 2 proteins, alpha2-macroglobulin and alpha1-antitrypsin, were shown to be reactive with aloe extract.