A Unique Sugar-binding Site Mediates the Distinct Anti-influenza Activity of Pig Surfactant Protein D

Pigs can act as intermediate hosts by which reassorted influenza A virus (IAV) strains can be transmitted to humans and cause pandemic influenza outbreaks. The innate host defense component surfactant protein D (SP-D) interacts with glycans on the hemagglutinin of IAV and contributes to protection against IAV infection in mammals. This study shows that a recombinant trimeric neck lectin fragment derived from porcine SP-D (pSP-D) exhibits profound inhibitory activity against IAV, in contrast to comparable fragments derived from human SP-D. Crystallographic analysis of the pSP-D fragment complexed with a viral sugar component shows that a unique tripeptide loop alters the lectin site conformation of pSP-D. Molecular dynamics simulations highlight the role of this flexible loop, which adopts a more stable conformation upon sugar binding and may facilitate binding to viral glycans through contact with distal portions of the branched mannoside. The combined data demonstrate that porcine-specific structural features of SP-D contribute significantly to its distinct anti-IAV activity. These findings could help explain why pigs serve as important reservoirs for newly emerging pathogenic IAV strains.     

Nest and colony-specific spectra in the weaver ant Oecophylla smaragdina

Animals in social groups need to differentiate between group members and others. In very large groups, such as those formed by many ant species, it is not possible to rely on individually specific cues to identify colonymates. Instead, recognition must be based on the colony-specific cues. Individual ant colonies tend to have a specific chemical gestalt that is maintained by the continual exchange of chemicals between workers. In very large polydomous colonies, the exchange of chemicals may be limited between nests within the colony, resulting in inter-nest variation in colony odour that might hinder identification of colonymates or conspecific intruders. We used near-infrared spectroscopy to explore variation in the chemical profile between and within colonies of the weaver ant Oecophylla smaragdina. We found that differences between colonies were reflected in the position, amplitude and width of spectral peaks, while differences between nests within colonies were reflected mainly in amplitude. Furthermore, in the context of colonymate recognition, the behaviour of the ants themselves was positively correlated with colony-specific spectral characteristics, rather than with nest-specific characteristics. Thus, colony spectra have features that are not obscured by intra-colonial variation and may potentially encode the chemical characteristics used by workers to identify colonymates.     

New cyclodextrin derivative 6-O-(2-hydroxybutyl)-β-cyclodextrin: preparation and its application in molecular binding and recognition

A new soluble cyclodextrin derivative 6-O-(2-hydroxybutyl)-β-cyclodextrin (6-HB-β-CD) was prepared. Its molecular binding and recognition ability were investigated with the comparison of β-cyclodextrin (β-CD), 2-O-(2-hydroxypropyl)-β-cyclodextrin (2-HP-β-CD), 6-O-(2-hydroxypropyl)-β-cyclodextrin (6-HP-β-CD), and 2-O-(2-hydroxybutyl)-β-cyclodextrin (2-HB-β-CD). The relationship between the complex stability constants and the possible structures of inclusion compounds was discussed with the interaction of hosts and guests, including the weak hydrophobic interactions, the size/shape matching, the steric hindrance, and the hydrophilic property.     

哺乳动物嗅觉与母性识别

嗅觉通讯在陆生哺乳动物母性识别中具有重要作用。通过嗅觉信息,早熟性动物(有蹄类)产后早期能够迅速建立专一性的母性识别和母子联系,并具有母性识别的敏感期。在敏感期内,分娩经验、催产素及一氧化氮等神经递质的释放有助于这种识别和联系的形成。多项研究表明,晚熟性动物(如啮齿类)母性识别的形成主要基于断乳前母兽与幼仔共处获得的熟悉性,产后早期不能迅速形成专一性的母性识别和母子联系,母兽对亲生幼仔和非亲生幼仔的选择性哺育不完全取决于识别。实验方法及识别的判定标准对研究啮齿类的母性识别尤其重要。包括人类在内的灵长类母亲产后只通过嗅觉信息即可以对婴儿进行识别。在哺乳动物的母性识别中,妊娠和分娩过程会诱导嗅觉系统的高度可塑性,有利于促进母亲对幼体气味的学习,但硬连接(hard-wired)路径也可能参与母性识别。     

The Caenorhabditis elegans bus-2 Mutant Reveals a New Class of O-Glycans Affecting Bacterial Resistance

Microbacterium nematophilum causes a deleterious infection of the C. elegans hindgut initiated by adhesion to rectal and anal cuticle. C. elegans bus-2 mutants, which are resistant to M. nematophilum and also to the formation of surface biofilms by Yersinia sp., carry genetic lesions in a putative glycosyltransferase containing conserved domains of core-1 β1,3-galactosyltransferases. bus-2 is predicted to act in the synthesis of core-1 type O-glycans. This observation implies that the infection requires the presence of host core-1 O-glycoconjugates and is therefore carbohydrate-dependent. Chemical analysis reported here reveals that bus-2 is indeed deficient in core-1 O-glycans. These mutants also exhibit a new subclass of O-glycans whose structures were determined by high performance tandem mass spectrometry; these are highly fucosylated and have a novel core that contains internally linked GlcA. Lectin studies showed that core-1 glycans and this novel class of O-glycans are both expressed in the tissue that is infected in the wild type worms. In worms having the bus-2 genetic background, core-1 glycans are decreased, whereas the novel fucosyl O-glycans are increased in abundance in this region. Expression analysis using a red fluorescent protein marker showed that bus-2 is expressed in the posterior gut, cuticle seam cells, and spermatheca, the first two of which are likely to be involved in secreting the carbohydrate-rich surface coat of the cuticle. Therefore, in the bus-2 background of reduced core-1 O-glycans, the novel fucosyl glycans likely replace or mask remaining core-1 ligands, leading to the resistance phenotype. There are more than 35 Microbacterium species, some of which are pathogenic in man. This study is the first to analyze the biochemistry of adhesion to a host tissue by a Microbacterium species.     

The 1.5 Å crystal structure of human receptor for advanced glycation endproducts (RAGE) ectodomains reveals unique features determining ligand binding

Interaction of the pattern recognition receptor, RAGE with key ligands such as advanced glycation end products (AGE), S100 proteins, amyloid β, and HMGB1 has been linked to diabetic complications, inflammatory and neurodegenerative disorders, and cancer. To help answer the question of how a single receptor can recognize and respond to a diverse set of ligands we have investigated the structure and binding properties of the first two extracellular domains of human RAGE, which are implicated in various ligand binding and subsequent signaling events. The 1.5-Å crystal structure reveals an elongated molecule with a large basic patch and a large hydrophobic patch, both highly conserved. Isothermal titration calorimetry (ITC) and deletion experiments indicate S100B recognition by RAGE is an entropically driven process involving hydrophobic interaction that is dependent on Ca²⁺ and on residues in the C′D loop (residues 54–67) of domain 1. In contrast, competition experiments using gel shift assays suggest that RAGE interaction with AGE is driven by the recognition of negative charges on AGE-proteins. We also demonstrate that RAGE can bind to dsDNA and dsRNA. These findings reveal versatile structural features of RAGE that help explain its ability to recognize of multiple ligands.     

Identification of Acidic pH-dependent Ligands of Pentameric C-reactive Protein

C-reactive protein (CRP) is a phylogenetically conserved protein; in humans, it is present in the plasma and at sites of inflammation. At physiological pH, native pentameric CRP exhibits calcium-dependent binding specificity for phosphocholine. In this study, we determined the binding specificities of CRP at acidic pH, a characteristic of inflammatory sites. We investigated the binding of fluid-phase CRP to six immobilized proteins: complement factor H, oxidized low-density lipoprotein, complement C3b, IgG, amyloid β, and BSA immobilized on microtiter plates. At pH 7.0, CRP did not bind to any of these proteins, but, at pH ranging from 5.2 to 4.6, CRP bound to all six proteins. Acidic pH did not monomerize CRP but modified the pentameric structure, as determined by gel filtration, 1-anilinonaphthalene-8-sulfonic acid-binding fluorescence, and phosphocholine-binding assays. Some modifications in CRP were reversible at pH 7.0, for example, the phosphocholine-binding activity of CRP, which was reduced at acidic pH, was restored after pH neutralization. For efficient binding of acidic pH-treated CRP to immobilized proteins, it was necessary that the immobilized proteins, except factor H, were also exposed to acidic pH. Because immobilization of proteins on microtiter plates and exposure of immobilized proteins to acidic pH alter the conformation of immobilized proteins, our findings suggest that conformationally altered proteins form a CRP-ligand in acidic environment, regardless of the identity of the protein. This ligand binding specificity of CRP in its acidic pH-induced pentameric state has implications for toxic conditions involving protein misfolding in acidic environments and favors the conservation of CRP throughout evolution.     

西藏巨柏核型的图象自动分析与识别的研究

我们应用图象自动分析和识别的原理和方法,建立了植物染色体自动分析CHROMHUK软件系统,并首次对西藏巨柏进行了核型自动分析,抽取了染色体多个特征多数:相对长度、臂比、着丝点指数、相对体密度和次缢痕相对长度.对247个巨柏体细胞进行多参数数据统计和分析,并设置95°.置信判别区域和树分类判别.实现了染色体自动配对和分类,并由计算机直接输出染色体的组型图和核型模式图.分析结果表明:巨柏体细胞的染色体数目为2n=22,按Levan的分类标准,其核型公式为2n=4m(SC)+16m+2sm.据Stabbins分类为1A型.     

A model for self-recognition and regulation of the incompatibility response of pollen

Summary Recent biochemical studies with Brassica indicate that the pollen grain has a primary role in the control of self incompatibility. Combining this new evidence with that from prior genetic, biochemical, and ultrastructural studies, a working model is hypothesized for the molecular events which occur during self recognition and the subsequent control of pollen germination. Self recognition is postulated to involve the interaction of a presynthesized, genotype-specific recognition molecule (effector) produced by the stigma with a presynthesized receptor molecule produced by and located in or on the pollen grain. The consequence of self recognition is a selective inhibition of pollen protein synthesis within about 2–4 minutes after imbibition. We deduced that protein synthesis is programmed to occur in pollen — unless interrupted as a consequence of self-recognition — and leads to the sequential production of opposing regulators: first a germination inhibitor (G-Inh), then a germination activator (G-Act). These regulators in turn control the activities of presynthesized, and probably sequestered enzymes required for germ tube formation. Sequential appearances of the G-Inh and G-Act occur unless synthesis of the G-Act is blocked as a result of self recognition. Thus, following a self pollination, recognition occurs in sufficient time to block production of the G-Act but not of the G-Inh, and inhibition of germination (incompatibility) results. For a cross pollination, there is no self recognition and production of the G-Act is unimpeded; it then nullifies the effect of the G-Inh and pollen germination (compatibility) results. The model and evidence for its support are discussed in detail.Department of Vegetable Crops Paper No. 719