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Staphylococcal Proteases Aid in Evasion of the Human Complement System.

Staphylococcus aureus is an opportunistic pathogen that presents severe health care concerns due to the prevalence of multiple antibiotic-resistant strains. New treatment strategies are urgently needed, which requires an understanding of disease causation mechanisms. Complement is one of the first lines of defense against bacterial pathogens, and S. aureus expresses several specific complement inh

Serglycin inhibits the classical and lectin pathways of complement via its glycosaminoglycan chains: Implications for multiple myeloma

Serglycin (SG) is a proteoglycan expressed by hematopoietic cells and is constitutively secreted by multiple myeloma (MM) cells. SG participates in the regulation of various inflammatory events. We found that SG secreted by human MM cell lines inhibits both the classical and lectin pathways of complement, without influencing alternative pathway activity. The inhibitory effect of SG is due to direc

A fine-tuned interaction between the trimeric autotransporter Haemophilus surface fibrils and vitronectin leads to serum resistance and adherence to respiratory epithelial cells.

Haemophilus influenzae type b (Hib) escapes the host immune system by recruitment of the complement regulator vitronectin that inhibits the formation of the membrane attack complex (MAC) by inhibiting C5b-C7 complex formation and C9 polymerization. We previously reported that Hib acquires vitronectin at the surface by using Haemophilus surface fibrils (Hsf). Here we studied in detail the interacti

Hydrodynamic trapping of molecules in lipid bilayers

In this work we show how hydrodynamic forces can be used to locally trap molecules in a supported lipid bilayer (SLB). The method uses the hydrodynamic drag forces arising from a flow through a conical pipette with a tip radius of 1-1.5 mu m, placed approximately 1 mu m above the investigated SLB. This results in a localized force-field that acts on molecules protruding from the SLB, yielding a hy

CD4+T-cell localization to the large intestinal mucosa during Trichuris muris infection is mediated by G alpha(i)-coupled receptors but is CCR6-and CXCR3-independent

P>Infection of mice with the gastrointestinal nematode Trichuris muris represents a valuable tool to investigate and dissect intestinal immune responses. Resistant mouse strains respond to T. muris infection by mounting a T helper type 2 response. Previous results have shown that CD4+ T cells play a critical role in protective immunity, and that CD4+ T cells localize to the infected large intestin

Efficient Time Recursive Coherence Spectrum Estimation

The coherence spectrum is of notable interest as a bivariate spectral measure in a variety of application, and the topic has lately attracted notable interest with the recent formulation of several high-resolution data adaptive estimators. In this work, we present computationally efficient time recursive implementations of the recent iterative adaptive approach (IAA) estimator, examining both the

Fine Mapping of the Interaction between C4b-Binding Protein and Outer Membrane Proteins LigA and LigB of Pathogenic Leptospira interrogans.

The complement system consists of more than 40 proteins that participate in the inflammatory response and in pathogen killing. Complement inhibitors are necessary to avoid the excessive consumption and activation of this system on host cells. Leptospirosis is a worldwide zoonosis caused by spirochetes from the genus Leptospira. Pathogenic leptospires are able to escape from complement activation b

A simple and sensitive method for lactose detection based on direct electron transfer between immobilised cellobiose dehydrogenase and screen-printed carbon electrodes

A rapid and simple approach of lactose analysis is proposed based on 3rd generation amperometric biosensors employing cellobiose dehydrogenase (CDH) from Trametes villosa or Phanerochaete sordida immobilised on screen-printed carbon electrodes (SPCEs). After optimisation of the working conditions of the biosensors - pH of the carrier buffer, flow rate and applied potential - the sensors were able

CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth

This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts overexpressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic st

C4b-binding protein and factor h compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack

Apoptotic cells have been reported to down- regulate membrane-bound complement regulatory proteins ( m- C- Reg) and to activate complement. Nonetheless, most apoptotic cells do not undergo complement- mediated lysis. Therefore, we hypothesized that fluid phase complement inhibitors would bind to apoptotic cells and compensate functionally for the loss of m- C- Reg. We observed that m- C- Reg are d

Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines.

Glycoprotein B (gB) is a major component in several vaccines that are under development for prevention of disease by cytomegalovirus. It contains multiple determinants that are targets for neutralizing antibodies. One of them is site I of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite conserved between different isolates. However, it is poorly immunogenic in natural in

Mass transfer in eccentric binaries: the new oil-on-water smoothed particle hydrodynamics technique

To measure the onset of mass transfer in eccentric binaries, we have developed a two-phase smoothed particle hydrodynamics (SPH) technique. Mass transfer is important in the evolution of close binaries, and a key issue is to determine the separation at which mass transfer begins. The circular case is well understood and can be treated through the use of the Roche formalism. To treat the eccentric

Genetic analysis of neuropathic pain-like behavior following peripheral nerve injury suggests a role of the major histocompatibility complex in development of allodynia

Neuropathic pain is a common consequence of damage to the nervous system. We here report a genetic analysis of development of neuropathic pain-like behaviors after unilateral photochemically-induced ischemic sciatic nerve injury in a panel of inbred rat strains known to display different susceptibility to autoimmune neuroinflammation. Pain behavior was initially characterized in Dark-Agouti (DA; R

Structure-function studies of the C3a-receptor: C-terminal serine and threonine residues which influence receptor internalization and signaling

The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-termin

Stellar encounters involving massive stars in young clusters

We model collisions between pre-main-sequence stars using a smoothed particle hydrodynamics method. Assuming that all collisions lead to simple mergers, we use derived merger cross-sections to calculate the time-scale to make a 50-M-circle dot star by collisions within the core of a stellar cluster as a function of stellar number density. We show that a 50-M-circle dot star may be produced in this

The IgD C(H)1 region contains the binding site for the human respiratory pathogen Moraxella catarrhalis IgD-binding protein MID.

The Moraxella catarrhalis IgD-binding protein (MID) has a unique specificity for human IgD, and the sequence with maximal IgD binding is located within the amino acids MID962-1200. In the present paper, we examined the MID binding site on IgD using a series of recombinant Ig. Full-length IgD, IgD F(ab')(2), and an IgD F(ab') C290R mutant lacking the inter-heavy-chain cysteine 290 were manufactured

Increased Sensitivity to Broadly Neutralizing Antibodies of End-Stage Disease R5 HIV-1 Correlates with Evolution in Env Glycosylation and Charge.

Induction of broadly neutralizing antibodies, such as the monoclonal antibodies IgGb12, 2F5 and 2G12, is the objective of most antibody-based HIV-1 vaccine undertakings. However, despite the relative conserved nature of epitopes targeted by these antibodies, mechanisms underlying the sensitivity of circulating HIV-1 variants to broadly neutralizing antibodies are not fully understood. Here we have