Comparison of the Aerodynamic Performance of Five Racing Bicycle Wheels by Means of CFD Calculations

Aerodynamic drag is the main source of losses in cycling so improving the bicycle aerodynamic is a fundamental key factor to increase the performance. The aim of this research is to evaluate and compare the aerodynamic performance of racing bicycle wheels by means of CFD RANS numerical models: it is based on a previous work that reported the development of the numerical model. The aim of this work is to assess the capability of CFD RANS simulations to predict the aerodynamic performance of modern racing bicycle wheels. Drag and side forces are resolved over the range of different yaw angles

Identification of an iron-sulfur cluster that modulates the enzymatic activity in NarE, a Neisseria meningitidis ADP-ribosyltransferase.

In prokaryotes, mono-ADP-ribose transfer enzymes represent a family of exotoxins that display activity in a variety of bacterial pathogens responsible for causing disease in plants and animals, including those affecting mankind, such as diphtheria, cholera, and whooping cough. We report here that NarE, a putative ADP-ribosylating toxin previously identified from Neisseria meningitidis, which shares structural homologies with Escherichia coli heat labile enterotoxin and toxin from Vibrio cholerae, possesses an iron-sulfur center. The recombinant protein was expressed in E. coli, and when purified at high concentration, NarE is a distinctive golden brown in color. Evidence from UV-visible spectrophotometry and EPR spectroscopy revealed characteristics consistent of an iron-binding protein. The presence of iron was determined by colorimetric method and by an atomic absorption spectrophotometer. To identify the amino acids involved in binding iron, a combination of site-directed mutagenesis and UV-visible and enzymatic assays were performed. All four cysteine residues were individually replaced by serine. Substitution of Cys(67) and Cys(128) into serine caused a drastic reduction in the E(420)/E(280) ratio, suggesting that these two residues are essential for the formation of a stable coordination. This modification led to a consistent loss in ADP-ribosyltransferase activity, while decrease in NAD-glycohydrolase activity was less dramatic in these mutants, indicating that the correct assembly of the iron-binding site is essential for transferase but not hydrolase activity. This is the first observation suggesting that a member of the ADP-ribosyltransferase family contains an Fe-S cluster implicated in catalysis. This observation may unravel novel functions exerted by this class of enzyme

Cupricyclins, Novel Redox-Active Metallopeptides Based on Conotoxins Scaffold

Highly stable natural scaffolds which tolerate multiple amino acid substitutions represent the ideal starting point for the application of rational redesign strategies to develop new catalysts of potential biomedical and biotechnological interest. The knottins family of disulphide-constrained peptides display the desired characteristics, being highly stable and characterized by hypervariability of the inter-cysteine loops. The potential of knottins as scaffolds for the design of novel copper-based biocatalysts has been tested by engineering a metal binding site on two different variants of an ω-conotoxin, a neurotoxic peptide belonging to the knottins family. The binding site has been designed by computational modelling and the redesigned peptides have been synthesized and characterized by optical, fluorescence, electron spin resonance and nuclear magnetic resonance spectroscopy. The novel peptides, named Cupricyclin-1 and -2, bind one Cu2+ ion per molecule with nanomolar affinity. Cupricyclins display redox activity and catalyze the dismutation of superoxide anions with an activity comparable to that of non-peptidic superoxide dismutase mimics. We thus propose knottins as a novel scaffold for the design of catalytically-active mini metalloproteins

Alzheimer's Aβ Peptides with Disease-Associated N-Terminal Modifications: Influence of Isomerisation, Truncation and Mutation on Cu2+ Coordination

coordination of various Aβ peptides has been widely studied. A number of disease-associated modifications involving the first 3 residues are known, including isomerisation, mutation, truncation and cyclisation, but are yet to be characterised in detail. In particular, Aβ in plaques contain a significant amount of truncated pyroglutamate species, which appear to correlate with disease progression. coordination modes between pH 6–9 with nominally the same first coordination sphere, but with a dramatically different pH dependence arising from differences in H-bonding interactions at the N-terminus. coordination of Aβ, which may be critical for alterations in aggregation propensity, redox-activity, resistance to degradation and the generation of the Aβ3–× (× = 40/42) precursor of disease-associated Aβ3[pE]–x species

Structural and Functional Consequences Induced by Post-Translational Modifications in α-Defensins.

HNP-1 is an antimicrobial peptide that undergoes proteolytic cleavage to become a mature peptide. This process represents the mechanism commonly used by the cells to obtain a fully active antimicrobial peptide. In addition, it has been recently described that HNP-1 is recognized as substrate by the arginine-specific ADP-ribosyltransferase-1. Arginine-specific mono-ADP-ribosylation is an enzyme-catalyzed post-translational modification in which NAD(+) serves as donor of the ADP-ribose moiety, which is transferred to the guanidino group of arginines in target proteins. While the arginine carries one positive charge, the ADP-ribose is negatively charged at the phosphate moieties at physiological pH. Therefore, the attachment of one or more ADP-ribose units results in a marked change of cationicity. ADP-ribosylation of HNP-1 drastically reduces its cytotoxic and antibacterial activities. While the chemotactic activity of HNP-1 remains unaltered, its ability to induce interleukin-8 production is enhanced. The arginine 14 of HNP-1 modified by the ADP-ribose is in some cases processed into ornithine, perhaps representing a different modality in the regulation of HNP-1 activitie

EPR and Electrochemical study of Copper Complexes with Phenanthrolines and Cinnamate ligands

Solid state and solution EPR and electrochemical studies have been carried out on a series of complexes of copper(II) with differently substituted Phenanthrolines and cinnamate ligands. Spectra were recorded on binary complexes with cinnamate ligand and on a series of ternary complexes with the same anion and 1,10-Phenanthroline, 2,9-dimethyl-1,10-o-Phenanthroline or 4,7-dimethyl-1,10-o-Phenanthroline additional ligands, respectively. The electrochemistry of the same copper complexes was studied in N,N-dimethylformamide solvent. The results of both EPR and electrochemical experimetns can be correlated with electronic and steric effects attributable to the methyl substituents on the Phenanthroline ligan

Performance of Waterborne Cu(II) Octanoate/Ethanolamine Wood Presevatives

Various aqueous wood preservative solutions containing Cu(II) in the form of copper(II) sulphate or copper(II) octanoate, ethanolamine and in one case octanoic acid were investigated by spectrophotometry, polarography and Electron Paramagnetic Resonance (EPR) spectroscopy. Results have shown the same coordination environment around Cu(II) in all solutions with ethanolamine. Computer simulation of the EPR spectra also revealed that the coordination in the first coordination sphere of copper is the same at low concentration of ethanolamine. At 20% ethanolamine concentration, a mixture of two complexes (one with two nitrogens and the other with three) could be detected. The active compound in the investigated ethanolamine containing solutions is the same when previously synthesised copper(II) octanoate was used, or when copper(II) sulphate and octanoic acid were utilized instead. Fungicidal and leaching experiments with the treated wood resulted in the same conclusion: it is not necessary to use pre-synthesised copper(II) octanoate for the preparation of waterborne copper/ethanolamine wood preservatives. Preservative preparation time and costs can be reduced by simply dissolving copper(II) sulphate and octanoic acid in aqueous ethanolamine solutions