Uptake and Metabolism of Choline by Rat Brain After Acute Choline Administration

The present study is concerned with the uptake and metabolism of choline by the rat brain. Intraperitoneal administration of choline chloride (4-60 mg/kg) caused a dose-dependent elevation of the plasma choline concentration from 11.8 to up to 165.2 microM within 10 min and the reversal of the negative arteriovenous difference (AVD) of choline across the brain to positive values at plasma choline levels of greater than 23 microM. Net choline release and uptake were linearly dependent on the plasma choline level in the physiological range of 10-50 microM, whereas the CSF choline level was significantly increased only at plasma choline levels of greater than 50 microM. The bolus injection of 60 mg/kg of [3H]choline chloride caused the net uptake of greater than 500 nmol/g of choline by the brain as calculated from the AVD, which was reflected in a minor increase of free choline level and a long-lasting increase of brain phosphorylcholine content, which paralleled the uptake curve. Loss of label from phosphorylcholine 30 min to 24 h after choline administration was accompanied by an increase of label in phosphatidylcholine, an indication of a delayed transfer of newly taken-up choline into membrane choline pools. In conclusion, homeostasis of brain choline is maintained by a complex system that interrelates choline net movements into and out of the brain and choline incorporation into and release from phospholipids.     

Searching new targets for anthelminthic strategies: Interference with glycosphingolipid biosynthesis and phosphorylcholine metabolism affects development of Caenorhabditis elegans

Nematode infections are amongst the most abundant diseases of man and animals. They are characterised by a low mortality but high morbidity, thus reflecting the adaptation of these parasites to their hosts. Resistance as well as severe side-effects and efficacies restricted to distinct larval stages or parasites of the anthelmithics used at present require the urgent development of new and more nematode-specific drugs, targeting enzymes of parasite restricted biosynthetic routes. Caenorhabditis elegans has been found to be a good model system for parasitic nematodes, drug screening and developmental studies. Structural analyses have revealed nematode-specific glycosphingolipid structures of the arthro-series, carrying in part, phosphorylcholine substituents. These biomolecules appear to play important roles in nematode development, fertility and survival within the host and are, therefore, good target-candidates for the development of new anthelminthic strategies. Here we show that RNAi experiments targeting enzymes of glycosphingolipid biosynthesis or choline metabolism result, in part, in a drastic reduction of fertility. We further tested various chemical inhibitors of these pathways and found significant effects on the development of the worms, resulting in developmental arrest, sterility and, in part, lethality. Such inhibitors can, therefore, help to define new classes of anthelminthics.     

Enhanced neurite outgrowth by human neurons grown on solid three-dimensional scaffolds

Growing and differentiating human stem cells in vitro can provide access to study the molecular mechanisms that control cellular development in a manner pertinent to human embryogenesis. To fully understand such processes, however, it is important to recreate culture conditions that most closely relate to those in living tissues. As step in this direction, we have developed a robust three-dimensional cell culture system using inert highly porous solid matrices manufactured from polystyrene that can be routinely used to study the differentiation of human pluripotent stem cell-derived neurons in vitro. Neurite outgrowth was significantly enhanced when neurons were grown in a three-dimensional environment compared to traditional flat surfaces and resulted in the formation of extensive neural networks. These data suggest that the topography within the culture environment can significantly alter cell development and will therefore be an important feature when investigating the potential of human stem cells.     

A new moisture-sensitive metal-coordination solids {[Cd(C4O4)(bipy)(H2O)2] · 3H2O}∞ (bipy=4,4-bipyridine)

A new mixed-ligands metal-coordination polymer, [Cd(C₄O₄)(bipy)(H₂O)₂] (1), (bipy=4,4^′-bipyridine), was synthesized under hydrothermal condition and characterized by X-ray diffraction method. A three-dimensional interpenetrating network with one-dimensional channels intercalating water molecules undergoes a reversible hydration-dehydration process upon a cooling-heating cycles associated with distinct color change and structural variation.     

Peptide microarrays for the characterization of antigenic regions of human chromogranin A

Microarraying peptides is a powerful proteomics technique for studying molecular recognition events. Since peptides have small molecular mass, they are not easily accessible when adsorbed onto solid supports. Moreover, peptides can lack a well-defined three-dimensional structure, and therefore a correct orientation is essential to promote the interaction with their target. In this work, we investigated the suitability as a peptide array substrate of a glass slide coated with a copolymer of N,N-dimethylacrylamide, N,N-acryloyloxysuccinimide, and [3-(methacryloyl-oxy)propyl]trimethoxysilyl. This polymeric surface was used as substrate for peptides in the characterization of linear antigenic sites of human chromogranin A, a useful tissue and serum marker for neuroendocrine tumors and a precursor of many biologically active peptides. The microarray support provided sufficient accessibility of the ligand, with no need for a spacer, as the polymer chains prevent interaction of immobilized peptides with substrate. In addition, the polymeric surface constitutes an aqueous micro-environment in which linear epitopes are freely exposed despite peptide random orientation. The results reported in this article are in accordance with those obtained in conventional ELISA assays using biotinylated and non-biotinylated peptides.     

Phase Grating from Ordered Polymer Lattices for Optica Image Preprocessing

The inverted retina of the human eye can beemulated by multilayer gratings from polymer latexparticles located in the image plane of opticalsystems. This so called OPTO-RETINA provides v. Laueinterference patterns in visible light with atrichromatic characteristic containing,simultaneously, local spatiotemporal direction anddistance information, which are relevant to 3Dspatial vision and 4D spatiotemporal Fouriercorrelator-optical preprocessing in shape andmotion analysis.As a first step in the realization of OPTO-RETINAproperties the formation of hexagonally orderedmonolayers of polystyrene latex sphereswith diameters in the~m range is reported and firstresults of diffraction and dispersion of white lightby these layers obtained by conoscopical opticalmicroscopy are presented.     

Solvent-responsiveness of PS–PEO binary mixed polymer brushes: a coarse-grained molecular dynamics study

Abstract

Systems of mixed polymer brushes (polystyrene–polyethylene oxide, PS–PEO) uniformly grafted on solid substrate were investigated by coarse-grained molecular dynamics simulations. The effects of grafting density and relatively degree of polymerisation of PS and PEO on the switching property of PS–PEO mixed polymer brushes in water and solvent are explored and discussed. Simulation results indicate that PS dominated the thickness of PS–PEO mixed polymer brushes in different solvents, which can be controlled by adjusting the grafting density. Brush heights of mixed PS–PEO polymer brushes fluctuate in different solvents when grafting density varies. The chemical composition of the very top surface of these mixed polymer brushes are largely determined by the relative polymerisation degree of PS and PEO.     

Fungal laccases as tools for the synthesis of new hybrid molecules and biomaterials

Laccase is a ligninolytic enzyme widely distributed in wood-rotting fungi and which is also found in a variety of molds and insects as well as some plants and bacteria. Its biological roles range from depolmerization of lignin, coal and humic acids via the oxidation of various mono- and diaromatic structures, to polymerization reactions and pigment formation in microbial cells or spores. Apart from its action in catabolic, depolymerizing and polymerizing processes, laccases have also been shown to be powerful enzymes for coupling two different molecules to create new low-molecular-weight products in high yield. In addition to their homomolecular coupling capabilities, laccases are also able to couple a hydroxylated aromatic substrate with a nonlaccase substrate of variable structure to create new heteromolecular hybrid molecules. Thus, laccases are increasingly finding applications in biotechnology in the fields of environment-friendly synthesis of fine chemicals and for the gentle derivatization of biologically active compounds e.g., antibiotics, amino acids, antioxidants, and cytostatics. Finally, oligomerization and polymerization reactions can lead to new homo- or heteropolymers and biomaterials. These may be useful in a wide range of applications including the production of polymers with antioxidative properties, the copolymerizing of lignin components with low-molecular mass compounds, the coating of cellulosic cotton fibers or wool, the coloring of hair and leathers, or the cross-linking and oligomerization of peptides.     

The importance of hydrogen bonding in the complexation of lanthanide ions by polymer-bound malonamide-type ligands

Polymer-bound malonate ligands modified with diethylenetriamine (DETA-MAm) are prepared and the lanthanide ion affinities from solutions of 0.001-8 M HCl are quantified. A mechanism is proposed. The affinities are not due to the triamine ligand alone or the adjacent carbonyl sites alone: protonation of the carbonyl oxygen triggers formation of an iminium ion and it acts as an ion-exchange site. Two competing reactions occur during binding: electrostatic attraction of [Ln(H₂O)_xCl₄]⁻ by the protonated ligand and (partial) loss of the waters of hydration. The affinity and selectivity are affected by substituents on the iminium (CNRR′(+)) ion. Research with tetramethylmalonamide showed that its two methyl groups at the iminium site weaken the positive charge and decrease its affinity for the chlorocomplexes of the later lanthanides; DETA-MAm has at its amide nitrogen only one −CH₂− (and one H) moiety and therefore is a stronger but less selective ligand since electrostatic attraction is more dominant in the overall mechanism. The higher affinities of malonate monoamidated with ethylenediamine (EDA-MAm) and decreased affinities for those amidated with ethanolamine (EA-MAm) suggest that the protonated -NH- stabilizes the lanthanide chlorocomplex.