Hard-core Yukawa model for two-dimensional charge stabilized colloids

The hyper-netted chain (HNC) and Percus-Yevick (PY) approximations are used to study the phase diagram of a simple hard-core Yukawa model of charge-stabilized colloidal particles in a two-dimensional system. We calculate the static structure factor and the pair distribution function over a wide range of parameters. Using the statics correlation functions we present an estimate for the liquid-solid phase diagram for the wide range of the parameters.Comment: 7 pages, 9figure

Tuning the structure of non-equilibrium soft materials by varying the thermodynamic driving force for crystal ordering

The official published version of the Article can be accessed from the link below - Copyright @ 2010 Royal Society of ChemistryThe present work explores the ubiquitous morphological changes in crystallizing systems with increasing thermodynamic driving force based on a novel dynamic density functional theory. A colloidal ‘soft’ material is chosen as a model system for our investigation since there are careful colloidal crystallization observations at a particle scale resolution for comparison, which allows for a direct verification of our simulation predictions. We particularly focus on a theoretically unanticipated, and generic, morphological transition leading to progressively irregular-shaped single crystals in both colloidal and polymeric materials with an increasing thermodynamic driving force. Our simulation method significantly extends previous ‘phase field’ simulations by incorporating a minimal description of the ‘atomic’ structure of the material, while allowing simultaneously for a description of large scale crystal growth. We discover a ‘fast’ mode of crystal growth at high driving force, suggested before in experimental colloidal crystallization studies, and find that the coupling of this crystal mode to the well-understood ‘diffusive’ or ‘slow’ crystal growth mode (giving rise to symmetric crystal growth mode and dendritic crystallization as in snowflakes by the Mullins–Sekerka instability) can greatly affect the crystal morphology at high thermodynamic driving force. In particular, an understanding of this interplay between these fast and slow crystal growth modes allows us to describe basic crystallization morphologies seen in both colloidal suspensions with increasing particle concentration and crystallizing polymer films with decreasing temperature: compact symmetric crystals, dendritic crystals, fractal-like structures, and then a return to compact symmetric single crystal growth again.This work has been supported by the EU FP7 Collaborative Project ENSEMBLE under Grant Agreement NMP4-SL-2008-213669 and by the Hungarian Academy of Sciences under contract OTKA-K-62588

HUS and atypical HUS

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by Shiga toxin-producing Escherichia coli (STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled complement activation, or as secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC, whereas aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation. Among the 30% to 50% of patients with HUS who have no detectable complement defect, some have either impaired diacylglycerol kinase epsilon (DGK epsilon) activity, cobalamin C deficiency, or plasminogen deficiency. Some have secondary HUS with a coexisting disease or trigger such as autoimmunity, transplantation, cancer, infection, certain cytotoxic drugs, or pregnancy. The common pathogenetic features in STEC-HUS, aHUS, and secondary HUS are simultaneous damage to endothelial cells, intravascular hemolysis, and activation of platelets leading to a procoagulative state, formation of microthrombi, and tissue damage. In this review, the differences and similarities in the pathogenesis of STEC-HUS, aHUS, and secondaryHUSare discussed. Commonfor the pathogenesis seems to be the vicious cycle of complement activation, endothelial cell damage, platelet activation, and thrombosis. This process can be stopped by therapeutic complement inhibition in most patients with aHUS, but usually not those with a DGK epsilon mutation, and some patients with STEC-HUS or secondary HUS. Therefore, understanding the pathogenesis of the different forms of HUS may prove helpful in clinical practice.Peer reviewe

The versatile functions of complement C3-derived ligands

The complement system is a major component of immune defense. Activation of the complement cascade by foreign substances and altered self-structures may lead to the elimination of the activating agent, and during the enzymatic cascade, several biologically active fragments are generated. Most immune regulatory effects of complement are mediated by the activation products of C3, the central component. The indispensable role of C3 in opsonic phagocytosis as well as in the regulation of humoral immune response is known for long, while the involvement of complement in T-cell biology have been revealed in the past few years. In this review, we discuss the immune modulatory functions of C3-derived fragments focusing on their role in processes which have not been summarized so far. The importance of locally synthesized complement will receive special emphasis, as several immunological processes take place in tissues, where hepatocyte-derived complement components might not be available at high concentrations. We also aim to call the attention to important differences between human and mouse systems regarding C3-mediated processes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Lt

FAD is a preferred substrate and an inhibitor of Escherichia coli general NAD(P)H:flavin oxidoreductase

Escherichia coli general NAD(P)H:flavin oxidoreductase (Fre) does not have a bound flavin cofactor; its flavin substrates (riboflavin, FMN, and FAD) are believed to bind to it mainly through the isoalloxazine ring. This interaction was real for riboflavin and FMN, but not for FAD, which bound to Fre much tighter than FMN or riboflavin. Computer simulations of Fre.FAD and Fre.FMN complexes showed that FAD adopted an unusual bent conformation, allowing its ribityl side chain and ADP moiety to form an additional 3.28 H-bonds on average with amino acid residues located in the loop connecting Fbeta5 and Falpha1 of the flavin-binding domain and at the proposed NAD(P)H-binding site. Experimental data supported the overlapping binding sites of FAD and NAD(P)H. AMP, a known competitive inhibitor with respect to NAD(P)H, decreased the affinity of Fre for FAD. FAD behaved as a mixed-type inhibitor with respect to NADPH. The overlapped binding offers a plausible explanation for the large K(m) values of Fre for NADH and NADPH when FAD is the electron acceptor. Although Fre reduces FMN faster than it reduces FAD, it preferentially reduces FAD when both FMN and FAD are present. Our data suggest that FAD is a preferred substrate and an inhibitor, suppressing the activities of Fre at low NADH concentrations

C3b deposition on human erythrocytes induces the formation of a membrane skeleton–linked protein complex

Decay-accelerating factor (DAF, also known as CD55), a glycosylphosphatidylinositol-linked (GPI-linked) plasma membrane protein, protects autologous cells from complement-mediated damage by inhibiting complement component 3 (C3) activation. An important physical property of GPI-anchored complement regulatory proteins such as DAF is their ability to translate laterally in the plasma membrane. Here, we used single-particle tracking and tether-pulling experiments to measure DAF lateral diffusion, lateral confinement, and membrane skeletal associations in human erythrocyte membranes. In native membranes, most DAF molecules exhibited Brownian lateral diffusion. Fluid-phase complement activation caused deposition of C3b, one of the products of C3 cleavage, onto erythrocyte glycophorin A (GPA). We then determined that DAF, C3b, GPA, and band 3 molecules were laterally immobilized in the membranes of complement-treated cells, and GPA was physically associated with the membrane skeleton. Mass spectrometry analysis further showed that band 3, α-spectrin, β-spectrin, and ankyrin were present in a complex with C3b and GPA in complement-treated cells. C3b deposition was also associated with a substantial increase in erythrocyte membrane stiffness and/or viscosity. We therefore suggest that complement activation stimulates the formation of a membrane skeleton–linked DAF-C3b-GPA–band 3 complex on the erythrocyte surface. This complex may promote the removal of senescent erythrocytes from the circulation