The immunopathogenesis of sepsis

Sepsis is a condition that results from a harmful or damaging host response to infection. Many of the components of the innate immune response that are normally concerned with host defences against infection can, under some circumstances, cause cell and tissue damage and hence multiple organ failure, the clinical hallmark of sepsis. Because of the high mortality of sepsis in the face of standard treatment, many efforts have been made to improve understanding of the dysregulation of the host response in sepsis. As a result, much has been learnt of the basic principles governing bacterial-host interactions, and new opportunities for therapeutic intervention have been revealed.     

Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus

The influenza pandemic of 1918-19 was responsible for about 50 million deaths worldwide. Modern histopathological analysis of autopsy samples from human influenza cases from 1918 revealed significant damage to the lungs with acute, focal bronchitis and alveolitis associated with massive pulmonary oedema, haemorrhage and rapid destruction of the respiratory epithelium. The contribution of the host immune response leading to this severe pathology remains largely unknown. Here we show, in a comprehensive analysis of the global host response induced by the 1918 influenza virus, that mice infected with the reconstructed 1918 influenza virus displayed an increased and accelerated activation of host immune response genes associated with severe pulmonary pathology. We found that mice infected with a virus containing all eight genes from the pandemic virus showed marked activation of pro-inflammatory and cell-death pathways by 24 h after infection that remained unabated until death on day 5. This was in contrast with smaller host immune responses as measured at the genomic level, accompanied by less severe disease pathology and delays in death in mice infected with influenza viruses containing only subsets of 1918 genes. The results indicate a cooperative interaction between the 1918 influenza genes and show that study of the virulence of the 1918 influenza virus requires the use of the fully reconstructed virus. With recent concerns about the introduction of highly pathogenic avian influenza viruses into humans and their potential to cause a worldwide pandemic with disastrous health and economic consequences, a comprehensive understanding of the global host response to the 1918 virus is crucial. Moreover, understanding the contribution of host immune responses to virulent influenza virus infections is an important starting point for the identification of prognostic indicators and the development of novel antiviral therapies.     

Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus

The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses, may be a feature shared by the virulent influenza viruses.     

Host recognition by the tobacco hornworm is mediated by a host plant compound

It is generally believed that animals make decisions about the selection of mates, kin or food on the basis of pre-constructed recognition templates. These templates can be innate or acquired through experience. An example of an acquired template is the feeding preference exhibited by larvae of the moth, Manduca sexta. Naive hatchlings will feed and grow successfully on many different plants or artificial diets, but once they have fed on a natural host they become specialist feeders. Here we show that the induced feeding preference of M. sexta involves the formation of a template to a steroidal glycoside, indioside D, that is present in solanaceous foliage. This compound is both necessary and sufficient to maintain the induced feeding preference. The induction of host plant specificity is at least partly due to a tuning of taste receptors to indioside D. The taste receptors of larvae fed on host plants show an enhanced response to indioside D as compared with other plant compounds tested.     

Proteome changes in the plasma of Papilio xuthus (Lepidoptera: Papilionidae): effect of parasitization by the endoparasitic wasp Pteromalus puparum (Hymenoptera: Pteromalidae)

Although the biochemical dissection of parasitoid-host interactions is becoming well characterized, the molecular knowledge concerning them is minimal. In order to understand the molecular bases of the host immune response to parasitoid attack, we explored the response of Papilio xuthus parasitized by the endoparasitic wasp Pteromalus puparum using proteomic approach. By examining the differential expression of plasma proteins in the parasitized and unparasitized host pupae by two-dimensional (2D) electrophoresis, 16 proteins were found to vary in relation to parasitization compared with unparasitized control samples. All of them were submitted to identification by mass spectrometry coupled with a database search. The modulated proteins were found to fall into the following functional groups: humoral or cellular immunity, detoxification, energy metabolism, and others. This study contributes insights into the molecular mechanism of the relationships between parasitoids and their host insects.     

带壳球形颗粒复合介质的有效介电响应

本文对线性（或非线性）的带壳球形颗粒分布于一线性基质的复合介质的线性（或非线性）有效介电响应进行了研究．以前的研究表明,在与核和壳的介电性质有关的条件下,这种三元复合体系（带壳）可等价于一个二元体系（不带壳）,然而,研究结果表明,当壳和基质的介电性质满足一定条件时,该三元复合体系也能等价于无壳实心球颗粒无规分布于原来的基质中的一个二元复合体系．这个等效的无壳实心球颗粒半径比上述三元复合体系中的球核颗粒大。若核颗粒为非线性材料,则满足一定条件时,该复合材料的体非线性介电响应也可得到增强．最后,我们讨论了带壳的球状颗粒复合介质的有效介电常数的依赖关系。     

A bacterial E3 ubiquitin ligase targets a host protein kinase to disrupt plant immunity

Many bacterial pathogens of plants and animals use a type III secretion system to deliver diverse virulence-associated 'effector' proteins into the host cell. The mechanisms by which these effectors act are mostly unknown; however, they often promote disease by suppressing host immunity. One type III effector, AvrPtoB, expressed by the plant pathogen Pseudomonas syringae pv. tomato, has a carboxy-terminal domain that is an E3 ubiquitin ligase. Deletion of this domain allows an amino-terminal region of AvrPtoB (AvrPtoB(1-387)) to be detected by certain tomato varieties leading to immunity-associated programmed cell death. Here we show that a host kinase, Fen, physically interacts with AvrPtoB(1-387 )and is responsible for activating the plant immune response. The AvrPtoB E3 ligase specifically ubiquitinates Fen and promotes its degradation in a proteasome-dependent manner. This degradation leads to disease susceptibility in Fen-expressing tomato lines. Various wild species of tomato were found to exhibit immunity in response to AvrPtoB(1-387 )and not to full-length AvrPtoB. Thus, by acquiring an E3 ligase domain, AvrPtoB has thwarted a highly conserved host resistance mechanism.     

Evasion of intracellular host defence by hepatitis C virus

Viral infection of mammalian cells rapidly triggers intracellular signalling events leading to interferon alpha/beta production and a cellular antiviral state. This 'host response' is our first line of immune defence against infection as it imposes several barriers to viral replication and spread. Hepatitis C virus (HCV) evades the host response through a complex combination of processes that include signalling interference, effector modulation and continual viral genetic variation. These evasion strategies support persistent infection and the spread of HCV. Defining the molecular mechanisms by which HCV regulates the host response is of crucial importance and may reveal targets for novel therapeutic strategies.     

Extensive surface diversity of a commensal microorganism by multiple DNA inversions.

The dynamic interactions between a host and its intestinal microflora that lead to commensalism are unclear. Bacteria that colonize the intestinal tract do so despite the development of a specific immune response by the host. The mechanisms used by commensal organisms to circumvent this immune response have yet to be established. Here we demonstrate that the human colonic microorganism, Bacteroides fragilis, is able to modulate its surface antigenicity by producing at least eight distinct capsular polysaccharides-a number greater than any previously reported for a bacterium-and is able to regulate their expression in an on-off manner by the reversible inversion of DNA segments containing the promoters for their expression. This means of generating surface diversity allows the organism to exhibit a wide array of distinct surface polysaccharide combinations, and may have broad implications for how the predominant human colonic microorganisms, the Bacteroides species, maintain an ecological niche in the intestinal tract.     

“蜜罐”技术在校园网络安全中的应用

本文着重讨论的"蜜罐"技术不同于以往的被动防御,而是采取主动防守,诱惑黑客上钩,最后抓捕黑客.主要从"蜜罐"技术的概念、关键技术、与传统的安全工具相比的优势、"蜜罐"技术的发展及其实现等各方面进行详细分析."蜜罐"主机采用伪装成多种主机或服务器系统,对黑客攻击具有主动应对策略,并能作出不同反应,因此提高了网络的安全性.     

Antigenic variation in trypanosomes

In its mammalian host, Trypanosoma brucei is able to change the antigenic character of its glycoprotein surface coat and so evade the host's immune response. This phenotypic change seems to occur spontaneously in 1 in 10,000 individuals but is not due to genetic mutation: host antibody is not necessary for its induction but plays a selective part in bringing about the gross changes in parasite numbers and antigenic character observed in the bloodstream by destroying the main component of what is actually a heterogeneous population. The infecting trypanosome population injected into the mammalian host by the tsetse fly vector may also be heterogeneous. Such heterogeneity complicates plans to vaccinate cattle and people against the African trypanosomes based on the premise that the metacyclic trypanosomes of a clone bear the same surface antigen.     

Effect of the endoparasitoidCampoletis chlorideae on phenoloxidase activity inHelicoverpa armigera hemolymph

Endoparasitoid wasps can develop inside permissive host due to their ability to overcome or to evade the host’s cellular and humoral immune response. Oviposition ofCampoletis chlorideae (Hymenoptera: Ichneumonidae) in larvae ofHelicoverpa armigera (Lepidoptera) was accompanied by inhibition of phenoloxidase (PO) activity and melanization reaction in host hemolymphin vitro. PO activity in host plasma was decreased about 83% 48 h post parasitization. A similar result was found when the host insect was injected with 0.5 wasp equivalent calyx fluid. This indicated that the calyx fluid was concerned with suppression of PO activity after parasitization. Furthermore, the prophenoloxidase (proPO) in host haemocytes could be activated by bovine trypsin in unparasitized insects, while it could not be activated in parasitized or calyx fluid-injected host. The results suggested that inhibition of PO activity by parasitization was related to the calyx fluid ofCampoletis chlorideae, and the components of calyx fluid (eg. polydnaviruses) perhaps suppressed the expression of proPO in hemolymph or accelerate the degradation of proPO.     

Infection of Wolbachia may improve the olfactory response of Drosophila

The endosymbiotic bacterium Wolbachia infects various insects and is primarily known for its ability to manipulate host reproduction.Recent investigations reveal that Wolbachia also affects the activity of somatic cells.We here demonstrated by trap method and T-maze that Wolbachia infection had signifi-cant impact on the olfactory response of Drosophila simulans.Wolbachia-infected flies took shorter time to enter the food trap and were more sensitive to odorant in T-maze than those uninfected controls.The t...     

Recognition of microorganisms and activation of the immune response

The mammalian immune system has innate and adaptive components, which cooperate to protect the host against microbial infections. The innate immune system consists of functionally distinct 'modules' that evolved to provide different forms of protection against pathogens. It senses pathogens through pattern-recognition receptors, which trigger the activation of antimicrobial defences and stimulate the adaptive immune response. The adaptive immune system, in turn, activates innate effector mechanisms in an antigen-specific manner. The connections between the various immune components are not fully understood, but recent progress brings us closer to an integrated view of the immune system and its function in host defence.     

基于iSCSI的虚拟化存储系统引擎设计

利用iSCSI存储技术标准设计了一个虚拟存储系统引擎VSSE(Virtual Storage System Engine).采用分层结构模型处理远程主机对存储区域网络中存储设备的I/O访问请求.实现基于快速以太网的存储区域网络中存储设备的虚拟化和透明访问,并取得了较好的I/O请求响应速度与I/O传输速度.     

结核分枝杆菌的免疫机制及抗原研究进展

结核分枝杆菌是一种胞内病原苗，在抗结核分枝杆菌感染中，活菌疫苗中的分泌蛋白起主要的免疫保护作用，它们激活宿主Ｔ细胞介导的细胞免疫，影响宿主免疫保护与病菌耐受性之间的不稳定平衡，决定宿主是否得病．结核分枝杆菌的特异性和保护性抗原的筛选为结核病的快速诊断及新型疫苗构建打下基础．     

Structural basis for signal transduction by the Toll/interleukin-1 receptor domains

Toll-like receptors (TLRs) and the interleukin-1 receptor superfamily (IL-1Rs) are integral to both innate and adaptive immunity for host defence. These receptors share a conserved cytoplasmic domain, known as the TIR domain. A single-point mutation in the TIR domain of murine TLR4 (Pro712His, the Lps(d) mutation) abolishes the host immune response to lipopolysaccharide (LPS), and mutation of the equivalent residue in TLR2, Pro681His, disrupts signal transduction in response to stimulation by yeast and gram-positive bacteria. Here we report the crystal structures of the TIR domains of human TLR1 and TLR2 and of the Pro681His mutant of TLR2. The structures have a large conserved surface patch that also contains the site of the Lps(d) mutation. Mutagenesis and functional studies confirm that residues in this surface patch are crucial for receptor signalling. The Lps(d) mutation does not disturb the structure of the TIR domain itself. Instead, structural and functional studies indicate that the conserved surface patch may mediate interactions with the down-stream MyD88 adapter molecule, and that the Lps(d) mutation may abolish receptor signalling by disrupting this recruitment.     

Sinorhizobium meliloti nifA gene exerts a pleiotropic effect on nodulation through the enhanced plant defense response

Sinorhizobium meliloti nifA gene is required for the expression of a bunch of nif and fix genes. Here, we report its pleiotropic effects on the nodule formation. Compared with wild type strain, nifA mutant sig- nificantly reduced nodule suppression rate in split-root system. The plants inoculated with mutant strain produced lower amount of daidzein and less necrotic cells on their roots. In addition, the defense genes failed to be evoked by nifA mutant at the early nodulation stage. These findings indicated that host defense response was one of the mechanisms mediated by nifA gene to regulate nodule formation during symbiosis. Even though nifA mutant could increase the number of nodules in host plant, it synthesized lower Nod factors than wild type. This suggested that nifA gene mediated multiple and diverse instances in nodulation formation.