A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4-6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism

Yersinia enterocolitica Serum Resistance Proteins YadA and Ail Bind the Complement Regulator C4b-Binding Protein

Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (O-ag) and outer core (OC) do not contribute directly to complement resistance. The aim of this study was to analyze a possible mechanism whereby Y. enterocolitica could inhibit the antibody-mediated classical pathway of complement activation. We show that Y. enterocolitica serotypes O:3, O:8, and O:9 bind C4b-binding protein (C4bp), an inhibitor of both the classical and lectin pathways of complement. To identify the C4bp receptors on Y. enterocolitica serotype O:3 surface, a set of mutants expressing YadA, Ail, O-ag, and OC in different combinations was tested for the ability to bind C4bp. The studies showed that both YadA and Ail acted as C4bp receptors. Ail-mediated C4bp binding, however, was blocked by the O-ag and OC, and could be observed only with mutants lacking these LPS structures. C4bp bound to Y. enterocolitica was functionally active and participated in the factor I-mediated degradation of C4b. These findings show that Y. enterocolitica uses two proteins, YadA and Ail, to bind C4bp. Binding of C4bp could help Y. enterocolitica to evade complement-mediated clearance in the human host

Diagnosis and Repair Technology of Damaged Elements of Casa Aircraft

Recently Polish Air Force has been equipped with new types of aircraft. New aircraft have many elements made of composites. Composites enable increasing performance but also pose new challenges. One of these challenges is the necessity of repairing after damage. This paper presents the results of the non-destructive inspection (MIA, conductivity, optical measurement ) of the C-295 plane after damage. Some parts made of composites and metal were damaged. In this paper, the authors propose a technology of repairing damaged parts

Dynamic protein adsorption at the polyurethane copolymer/water interface

Polyurethanes (PU) and their polymeric derivatives are widely used in the manufacturing of medical devices. It is important to understand how protein adsorbs onto PU materials as this molecular process directly implicates surface biocompatibility. In this work, we compared protein adsorption at the PU film surfaces with that from the hydrophilic silicon oxide. Two PU polymers were used, a commercial polyurethane (PUA) and a novel poly(carbonate-urea) urethane matrix containing silsesquioxanes (PU4). AFM imaging revealed micro-domain segregation on both PU surfaces, but the incorporation of pendent silsesquioxanes made the PU4 surface much rougher, with the outer surface comprised of soft upper PU segments and lower PU-silsesquioxane hard segments. It appeared that fibrinogen was preferable to adsorb onto the upper soft PU segments. The spectroscopic ellipsometry (SE) measurements at the PU film/solution interface showed that human serum albumin (HSA) adsorption was little affected by surface chemistry whilst fibrinogen adsorption was much greater on the two PU surfaces indicating a strong surface effect. Further studies revealed that HSA adsorption was reversible on hydrophilic SiO2 against changes in pH from 5 to 7, but irreversible on the two PU surfaces. In contrast, fibrinogen adsorption against the same pH cycling was found to be irreversible on all three surfaces. The different extent of irreversibility was clearly indicative of different interfacial interactions. Sequential protein adsorption revealed that the PU4 surface shared similar physiochemical properties to the SiO2 surface, demonstrating the success in incorporating the siloxane pendant nanocages. The knowledge of protein surface structure and behaviour may lead to the development of effective means to control surface biocompatibility

Composite Aerospace Structure Monitoring with use of Integrated Sensors

One major challenge confronting the aerospace industry today is to develop a reliable and universal Structural Health Monitoring (SHM) system allowing for direct aircraft inspections and maintenance costs reduction. SHM based on guided Lamb waves is an approach capable of addressing this issue and satisfying all the associated requirements. This paper presents an approach to monitoring damage growth in composite aerospace structures and early damage detection. The main component of the system is a piezoelectric transducers (PZT) network integrated with composites. This work describes sensors’ integration with the structure. In particular, some issues concerning the mathematical algorithms giving information about damage from the impact damage presence and its growth are discussed