Age- and Diabetes-Related Changes in the Free Fatty Acid Composition of the Human Stratum Corneum.

Of particular importance for Stratum corneum (SC) lipids are the free fatty acids (FFAs). Age-related changes of the SC structure lead to diminished capacity for barrier compensation. The aims of this cross-sectional study were to identify even-numbered especially odd-numbered FFAs within the intercorneocytic lamellar lipid structures of the SC and to explore age- and diabetes-related changes in FFAs. Gas chromatography - flame ionisation detection was used to qualitatively and quantitatively assess FFAs extracted from the SC. 110 subjects aged over 60 years (elderly/healthy), 110 subjects aged 18-40 (young/healthy) and 38 subjects with diabetes mellitus aged 18-40 (young/diabetic) were investigated. Overall, odd-numbered FFAs comprised about 21, 23 and 24% of total FFAs in subgroups elderly/healthy, young/healthy and young/diabetic. The most abundant short-chain FFAs were C16: 0 and C18: 0 and long-chain FFAs were C24: 0 and C26: 0. Only levels of C15: 0 and C17: 0 decreased with age. In contrast, levels of C18: 2 and C19 were significantly decreased and levels of C15, C17, C18: 1 and C23 were significantly increased in young diabetic subjects. In general, compared with younger healthy subjects, FFA composition was only partly significantly altered in older healthy subjects but was significantly altered in younger diabetic subjects.

Sensitization of NO-Releasing Ruthenium Complexes to Visible Light.

We report a combined spectroscopical-theoretical investigation on the photosensitization of transition metal nitrosyl complexes. For this purpose, ruthenium nitrosyl complexes based on tetradentate biscarboxamide ligands were synthesized. A crystal structure analysis of a lithium-based ligand intermediate is described. The Ru complexes have been characterized regarding their photophysical and nitric oxide (NO) releasing properties. Quantum chemical calculations have been performed to unravel the influence of the biscarboxamide ligand frame with respect to the molecular electronic properties of the NO-releasing pathway. A quantitative measure for the ligand design within photosensitized Ru complexes is introduced and evaluated spectroscopically and theoretically by using time-dependent density functional theory.

Cascade autohydrolysis of Alzheimer's Aß peptides.

Protein/peptide self-assembly into amyloid structures associates with major neurodegenerative disorders such as Alzheimer's disease (AD). Soluble assemblies (oligomers) of the Aß peptide and their aggregates are perceived as neurotoxic species in AD. While screening for synthetic cleavage agents that could break down such aberrant assemblies through hydrolysis, we observed that the assemblies of Aß oligopeptides, containing the nucleation sequence Aß14-24 (H14QKLVFFAEDV24), could act as cleavage agents by themselves. Autohydrolysis showed a common fragment fingerprint among various mutated Aß14-24 oligopeptides, Aß12-25-Gly and Aß1-28, and full-length Aß1-40/42, under physiologically relevant conditions. Primary endoproteolytic autocleavage at the Gln15-Lys16, Lys16-Leu17 and Phe19-Phe20 positions was followed by subsequent exopeptidase self-processing of the fragments. Control experiments with homologous d-amino acid enantiomers Aß12-25-Gly and Aß16-25-Gly showed the same autocleavage pattern under similar reaction conditions. The autohydrolytic cascade reaction (ACR) was resilient to a broad range of conditions (20-37 °C, 10-150 µM peptide concentration at pH 7.0-7.8). Evidently, assemblies of the primary autocleavage fragments acted as structural/compositional templates (autocatalysts) for self-propagating autohydrolytic processing at the Aß16-21 nucleation site, showing the potential for cross-catalytic seeding of the ACR in larger Aß isoforms (Aß1-28 and Aß1-40/42). This result may shed new light on Aß behaviour in solution and might be useful in the development of intervention strategies to decompose or inhibit neurotoxic Aß assemblies in AD.

Factors affecting economies of scale in combined sewer systems.

A generic model is introduced that represents the combined sewer infrastructure of a settlement quantitatively. A catchment area module first calculates the length and size distribution of the required sewer pipes on the basis of rain patterns, housing densities and area size. These results are fed into the sewer-cost module in order to estimate the combined sewer costs of the entire catchment area. A detailed analysis of the relevant input parameters for Swiss settlements is used to identify the influence of size on costs. The simulation results confirm that an economy of scale exists for combined sewer systems. This is the result of two main opposing cost factors: (i) increased construction costs for larger sewer systems due to larger pipes and increased rain runoff in larger settlements, and (ii) lower costs due to higher population and building densities in larger towns. In Switzerland, the more or less organically grown settlement structures and limited land availability emphasise the second factor to show an apparent economy of scale. This modelling approach proved to be a powerful tool for understanding the underlying factors affecting the cost structure for water infrastructures.

Computational Evolution of Threonine-Rich ß-Hairpin Peptides Mimicking Specificity and Affinity of Antibodies.

The development of recognition molecules with antibody-like properties is of great value to the biotechnological and bioanalytical communities. The recognition molecules presented here are peptides with a strong tendency to form ß-hairpin structures, stabilized by alternate threonines, which are located at one face of the peptide. Amino acids at the other face of the peptide are available for interaction with the target molecule. Using this scaffold, we demonstrate that recognition molecules can efficiently be designed in silico toward four structurally unrelated proteins, GFP, IL-1ß, IL-2, and IL-6. On solid support, 10 different antibody-mimetic recognition molecules were synthesized. They displayed high affinity and no cross-reactivity, as observed by fluorescence microscopy. Stabilized variants were readily obtained by incorporation of azido acids and propargylglycine followed by cyclization via the Cu(I)-catalyzed alkyne-azide cycloaddition reaction. As this new class of antibody mimics can be designed toward essentially any protein, the concept is believed to be useful to a wide range of technologies. Here, their use in protein separation and in the detection of proteins in a sandwich-type assay is demonstrated.