Morphometry and Stiffness of Red Blood Cells—Signatures of Neurodegenerative Diseases and Aging

Human red blood cells (RBCs) are unique cells with the remarkable ability to deform, which is crucial for their oxygen transport function, and which can be significantly altered under pathophysiological conditions. Here we performed ultrastructural analysis of RBCs as a peripheral cell model, looking for specific signatures of the neurodegenerative pathologies (NDDs)—Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD), utilizing atomic force (AFM) and conventional optical (OM) microscopy. We found significant differences in the morphology and stiffness of RBCs isolated from patients with the selected NDDs and those from healthy individuals. Neurodegenerative pathologies’ RBCs are characterized by a reduced abundance of biconcave discoid shape, lower surface roughness and a higher Young’s modulus, compared to healthy cells. Although reduced, the biconcave is still the predominant shape in ALS and AD cells, while the morphology of PD is dominated by crenate cells. The features of RBCs underwent a marked aging-induced transformation, which followed different aging pathways for NDDs and normal healthy states. It was found that the diameter, height and volume of the different cell shape types have different values for NDDs and healthy cells. Common and specific morphological signatures of the NDDs were identified.     

ICA1L Is Associated with Small Vessel Disease: A Proteome-Wide Association Study in Small Vessel Stroke and Intracerebral Haemorrhage

Small vessel strokes (SVS) and intracerebral haemorrhages (ICH) are acute outcomes of cerebral small vessel disease (SVD). Genetic studies combining both phenotypes have identified three loci associated with both traits. However, the genetic cis-regulation at the protein level associated with SVD has not been studied before. We performed a proteome-wide association study (PWAS) using FUSION to integrate a genome-wide association study (GWAS) and brain proteomic data to discover the common mechanisms regulating both SVS and ICH. Dorsolateral prefrontal cortex (dPFC) brain proteomes from the ROS/MAP study (N = 376 subjects and 1443 proteins) and the summary statistics for the SVS GWAS from the MEGASTROKE study (N = 237,511) and multi-trait analysis of GWAS (MTAG)-ICH–SVS from Chung et al. (N = 240,269) were selected. We performed PWAS and then a co-localization analysis with COLOC. The significant and nominal results were validated using a replication dPFC proteome (N = 152). The replicated results (q-value < 0.05) were further investigated for the causality relationship using summary data-based Mendelian randomization (SMR). One protein (ICA1L) was significantly associated with SVS (z-score = −4.42 and p-value = 9.6 × 10⁻⁶) and non-lobar ICH (z-score = −4.8 and p-value = 1.58 × 10⁻⁶) in the discovery PWAS, with a high co-localization posterior probability of 4. In the validation PWAS, ICA1L remained significantly associated with both traits. The SMR results for ICA1L indicated a causal association of protein expression levels in the brain with SVS (p-value = 3.66 × 10⁻⁵) and non-lobar ICH (p-value = 1.81 × 10⁻⁵). Our results show that the association of ICA1L with SVS and non-lobar ICH is conditioned by the cis-regulation of its protein levels in the brain.     

Processing of Particle-Stabilized Wet Foams Into Porous Ceramics

Direct foaming of colloidal suspensions is a simple and versatile approach for the fabrication of macroporous ceramic materials. Wet foams produced by this method can be stabilized by long-chain surfactants or by colloidal particles. In this work, we investigate the processing of particle-stabilized wet foams into crack-free macroporous ceramics. The processing steps are discussed with particular emphasis on the consolidation and drying process of wet foams. Macroporous alumina ceramics prepared using different consolidation and drying methods are compared in terms of their final microstructure, porosity, and compressive strength. Consolidation of the wet foam by particle coagulation before drying resulted in porous alumina with a closed-cell structure, a porosity of 86.5%, an average cell size of 35 μm, and a remarkable compressive strength of 16.3 MPa. On the other hand, wet foams consolidated via gelation of the liquid within the foam lamella led to porous structures with interconnected cells in the size range from 100 to 150 μm. The tailored microstructure and high mechanical strength of the macroporous ceramics can be of interest for the manufacture of bio-scaffolds, thermal insulators, impact absorbers, separation membranes, and light weight ceramics.     

Modeling and biological investigations of an unusual behavior of novel synthesized acridine-based polyamine ligands in the binding of double helix and G-quadruplex DNA

Three novel 2,7-substituted acridine derivatives were designed and synthesized to investigate the effect of this functionalization on their interaction with double-stranded and G-quadruplex DNA. Detailed investigations of their ability to bind both forms of DNA were carried out by using spectrophotometric, electrophoretic, and computational approaches. The ligands in this study are characterized by an open-chain (L1) or a macrocyclic (L2, L3) framework. The aliphatic amine groups in the macrocycles are joined by ethylene (L2) or propylene chains (L3). L1 behaved similarly to the lead compound m-AMSA, efficiently intercalating into dsDNA, but stabilizing G-quadruplex structures poorly, probably due to the modest stabilization effect exerted by its protonated polyamine chains. L2 and L3, containing small polyamine macrocyclic frameworks, are known to adopt a rather bent and rigid conformation; thus they are generally expected to be sterically impeded from recognizing dsDNA according to an intercalative binding mode. This was confirmed to be true for L3. Nevertheless, we show that L2 can give rise to efficient π-π and H-bonding interactions with dsDNA. Additionally, stacking interactions allowed L2 to stabilize the G-quadruplex structure: using the human telomeric sequence, we observed the preferential induction of tetrameric G-quadruplex forms. Thus, the presence of short ethylene spacers seems to be essential for obtaining a correct match between the binding sites of L2 and the nucleobases on both DNA forms investigated. Furthermore, current modeling methodologies, including docking and MD simulations and free energy calculations, provide structural evidence of an interaction mode for L2 that is different from that of L3; this could explain the unusual stabilizing ability of the ligands (L2>L3>L1) toward G-quadruplex that was observed in this study.     

Porous poly(2-hydroxyethyl acrylate) hydrogels prepared by radical polymerisation with methanol as diluent

Dynamic-mechanical and water sorption properties of porous and non-porous hydrogels have been studied as a function of their porosity and crosslinking density. Porous hydrogels with different crosslinking densities were prepared by co-polymerisation of 2-hydroxyethyl acrylate and ethyleneglycol dimethacrylate in solution in methanol. Pores were formed due to the segregation of the solvent from the polymer network during the polymerisation process. The porosity of the samples was observed by scanning electron microscopy. The pores collapse during the drying process after polymerisation but they reopen when the xerogel is immersed in liquid water. Bulk polymer networks with varying crosslinking densities were also synthesised and used as a reference in the analysis of the porous hydrogels. Water sorption from the gas phase and from the liquid phase was studied by means of equilibrium sorption isotherms and immersion experiments, respectively. Dynamic-mechanical spectroscopy conducted on the xerogels shows that the elastic modulus in the rubber-like state highly depends on the amount of solvent used in the polymerisation what is attributed to the presence of discontinuity surfaces in the xerogel although the pores are closed.     

Route instructions in map-based human–human and human–computer dialogue: A comparative analysis

When conveying information about spatial situations and goals, speakers adapt flexibly to their addressee in order to reach the communicative goal efficiently and effortlessly. Our aim is to equip a dialogue system with the abilities required for such a natural, adaptive dialogue. In this paper we investigate the strategies people use to convey route information in relation to a map by presenting two parallel studies involving human–human and human–computer interaction. We compare the instructions given to a human interaction partner with those given to a dialogue system which reacts by basic verbal responses and dynamic visualization of the route in the map. The language produced by human route givers is analyzed with respect to a range of communicative as well as cognitively crucial features, particularly perspective choice and references to locations across levels of granularity. Results reveal that speakers produce systematically different instructions with respect to these features, depending on the nature of the interaction partner, human or dialogue system. Our further analysis of clarification and reference resolution strategies produced by human route followers provides insights into dialogue strategies that future systems should be equipped with.     

Photosynthetic membranes, 21. Immobilization of catalase by photochemically grafted ultrafiltration membranes

Catalase has been immobilized in membranes prepared by photoinduced grafting onto microporous polymeric supports and its catalytic activity on hydrogen peroxide decomposition has been studied under ultrafiltration conditions by means of a recirculation apparatus. The membranes showed a very good catalytic performance and the enzyme reaction took place exclusively within the membrane structure. Initial reaction rates measured in the temperature range 5 – 35°C as a function of both substrate concentration and enzyme amount immobilized per unit membrane surface indicate that the mechanism of action of catalase is not altered after immobilization.     

Phase Equilibria in the System HfO2–Y2O3–CaO

Phase equilibria in the system HfO₂–Y₂O₃–CaO were studied in the temperature range 1250° to 2850°C by both experimental methods (X-ray phase analysis at 20° to 2000°C, petrography, annealing and quenching, differential thermal analysis in He at temperatures to 2500°C, thermal analysis in air using a solar furnace at temperatures to 3000°C, and electron microprobe X-ray analysis) and theoretical means (development of a mathematical model for the liquidus surface by means of the reduced polynomial method). Phase equilibria were determined by the structure of the restricting binary systems. No ternary compounds were found. The liquidus was characterized by the presence of six four-phase, invariant equilibria. Solid solutions were based on monoclinic (M), tetragonal (T), and cubic (F) modifications of HfO₂; C and H forms of Y₂O₃; CaO; and CaHfO₃ that crystallized in two polymorphous modifications, namely, the cubic and rhombic perovskite-type structure.     

Dispersing Behavior of Hydroxyapatite Powders Produced by Wet-Chemical Synthesis

Three hydroxyapatite powders with different surface properties were produced by wet-chemical synthesis and characterized. The electrokinetic properties of powders dispersed in water were investigated by electroacoustic spectroscopy measurements. The different surface reactivity (pH_iep and ζ potential versus pH curves) was related to the interplay of dissolution and adsorption of Ca²⁺ ions. With a view toward the preparation of porous bodies by sponge impregnation, the behavior of powder suspensions was studied. Four deflocculants were tested, and the optimum dispersing conditions for each powder were found. Anionic polyelectrolytes resulted in the best effective dispersing agent, with different optimum amounts added to the suspensions.     

Stability of a chitosan layer deposited onto a polyethylene surface

A two‐step procedure was applied to obtain antimicrobial films; this procedure involved a corona treatment of the polyethylene (PE) surface and its chemical activation with 1‐ethyl‐3‐[3‐dimethylaminopropyl] carbodiimide hydrochloride and N‐hydroxysuccinimide, and this led to the covalent bonding of chitosan on the PE surface. Electrochemical methods were used to investigate the stability of the deposited chitosan layer. The potentiometric and polyelectrolyte titrations showed that some amount of chitosan desorbed faster from the surface until equilibrium was reached and also that the grafted chitosan layer was more stable than the physically adsorbed one. The chitosan immobilized on the PE surface exhibited the expected antibacterial activity when tested against three bacteria, which included two Gram‐negative bacteria, Salmonella enteritidis and Escherichia coli, and one Gram‐positive bacterium, Listeria monocytogenes. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 2444–2457, 2013