Wie nachhaltig prägen uns politische Systeme? Evidenz aus der zweiten Dekade des Wiedervereinigungsprozesses

Der vorliegende Beitrag untersucht die „mentalen“ Diskrepanzen und Unterschiede in der Auffassung ökonomisch relevanter Präferenzparameter wie Vertrauen und Risikoeinstellung zwischen Ost- und Westdeutschen und geht der Frage nach: Ist Konvergenz bei den untersuchten Größen zwischen Ost und West zu beobachten? Im Ergebnis lässt sich feststellen, dass tatsächlich in einigen ökonomisch relevanten Dimensionen auch nach 20 Jahren Wiedervereinigungsprozess noch Ost-West-Unterschiede bestehen. Hinsichtlich der Risikoeinstellung wurde der Annäherungsprozess in der zweiten Dekade nach der Wiedervereinigung abgeschlossen. Für das allgemeinste Maß sozialen Vertrauens wird vollständige Konvergenz voraussichtlich in etwa zehn Jahren erreicht. Für Ost-West-Unterschiede in der Wahrnehmung von Fairness und Kooperationsbereitschaft ist bisher keine statistisch signifikante Annäherung messbar.

Performance Oriented Functionalisation of Concrete: an Integrated Approach for Prevention in Construction

The long-term preservation and the future-oriented development of the infrastructure are of utmost importance for every country in the world. An increasing failure of infrastructure underpins a tremendous need for action. The reasons for this unsatisfactory situation are various, but certainly among them is often an insufficient performance of the building materials. This holds particularly true for reinforced concrete and its additives, which are nowadays commonly developed by empirical research. Almost all shortcomings of concrete durability are related to the transport of detrimental substances into the pore system. In this regard, a promising approach to prevent chemical deterioration processes is a functionalisation of the pore system by means of organosilicon-based surface treatments in order to hamper the uptake of aggressive aqueous solutions. However, little is known about the reaction mechanisms and the nature of the reaction products associated with such measures. However, this is necessary to obtain reliable information about their performance and ideally to develop these technologies further in a more target-oriented manner. The insufficient understanding of these processes has its origins in the inability of investigations of the reaction course of silicon organic compounds in the pore structure of cement-based systems and their underlying physical and chemical principles. This applies in particular to film-forming reactions in alkaline environments of the pore structure, which lead to functionalization (e.g. hydrophobic effect). The approach of this study is therefore to investigate the reaction products in model systems using mass spectrometry and to explain the course of the reaction by means of computational chemistry. In this way, reaction products of different reaction steps of the condensation of specific components into larger oligomers were characterized and the reaction sequence was explained by molecular modelling. These results contribute to a deeper understanding of the reactions and types of reaction products of organosilicon compounds used to improve the properties of cement-bound materials. This promotes further steps towards the performance-oriented development of such surface protection technologies

Identification of the amino acid labionin and its desulfurised derivative in the type-III lantibiotic LabA2 by means of GC/MS

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.A GC-MS method for the rapid and unambiguous identification of the amino acid labionin (Lab) occurring in type-III lantibiotics is presented. This method will constitute a valuable tool for the characterisation and structure elucidation of labyrinthopeptins and their differentiation from lanthionine-type lantibiotics

Structure of the pheromone peptide of the Staphylococcus epidermidis agr system

AbstractThe agr quorum-sensing system is responsible for the regulation of several virulence factors in staphylococci, with an extracellular pheromone peptide as signalling molecule. By monitoring the biological activity of synthetic peptides, it could be demonstrated that the pheromone of the agr system in Staphylococcus epidermidis is an octapeptide containing a thiolester linkage between the central cysteine and the C-terminal carboxyl group. The peptide was active at nanomolar concentrations. The N-terminus of the peptide pheromone, which is encoded as part of a protein precursor, proved to be crucial for biological activity

Extensive structure‐activity relationship study of albicidin’s C‐terminal dipeptidic p‐aminobenzoic acid moiety

Albicidin is a recently described natural product that strongly inhibits bacterial DNA gyrase. The pronounced activity, particularly against Gram‐negative bacteria, turns it into a promising lead structure for an antibacterial drug. Hence, structure–activity relationship studies are key for the in‐depth understanding of structural features/moieties affecting gyrase inhibition, antibacterial activity and overcoming resistance. The 27 newly synthesized albicidins give profound insights into possibilities for variations of the C‐terminus. Furthermore, in the present study, a novel derivative has been identified as overcoming resistance posed by the Klebsiella‐protease AlbD. Structural modifications include, for example, azahistidine replacing the previous instable cyanoalanine as the central amino acid, as well as a triazole amide bond isostere between building blocks D and E.BMBF, 03VP00030, Validierung einer neuen antibakteriellen Wirkstoffklasse - AlbiPharmTU Berlin, Open-Access-Mittel - 201

Bacillus subtilis as heterologous host for the secretory production of the non-ribosomal cyclodepsipeptide enniatin

The heterologous expression of genes or gene clusters in microbial hosts, followed by metabolic engineering of biosynthetic pathways, is key to access industrially and pharmaceutically relevant compounds in an economically affordable and sustainable manner. Therefore, platforms need to be developed, which provide tools for the controlled synthesis of bioactive compounds. The Gram-positive bacterium Bacillus subtilis is a promising candidate for such applications, as it is generally regarded as a safe production host, its physiology is well investigated and a variety of tools is available for its genetic manipulation. Furthermore, this industrially relevant bacterium provides a high secretory potential not only for enzymes but also for primary and secondary metabolites. In this study, we present the first heterologous expression of an eukaryotic non-ribosomal peptide synthetase gene (esyn) coding for the biosynthesis of the small molecule enniatin in B. subtilis. Enniatin is a pharmaceutically used cyclodepsipeptide for treatment of topical bacterial and fungal infections. We generated various enniatin-producing B. subtilis strains, allowing for either single chromosomal or plasmid-based multi-copy expression of the esyn cluster under the control of an acetoin-inducible promoter system. Optimization of cultivation conditions, combined with modifications of the genetic background and multi-copy plasmid-based esyn expression, resulted in a secretory production of enniatin B. This work presents B. subtilis as a suitable host for the expression of heterologous eukaryotic non-ribosomal peptide synthetases (NRPS) clusters

Application of a Rapid and Integrated Analysis System (RIAS) as a High-Throughput Processing Tool for In Vitro ADME Samples by Liquid Chromatography/Tandem Mass Spectrometry

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Over the past decade, drug discovery programs have started to address the optimization of key ADME properties already at an early stage of the process. Hence, analytical chemists have been confronted with tremendously rising sample numbers and have had to develop methodologies accelerating quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS). This article focuses on the application of a generic and fully automated LC/MS/MS, named Rapid and Integrated Analysis System (RIAS), as a high-throughput platform for the rapid quantification of drug-like compounds in various in vitro ADME assays. Previous efforts were dedicated to the setup and feasibility study of a workflow-integrated platform combining a modified high-throughput liquid handling LC/MS/MS system controlled by a customized software interface and a customized data-processing and reporting tool. Herein the authors present an extension of this previously developed basic application to a broad set of ADME screening campaigns, covering CYP inhibition, Caco-2, and PAMPA assays. The platform is capable of switching automatically between various ADME assays, performs MS compound optimization if required, and provides a speed of 8 s from sample to sample, independently of the type of ADME assay. Quantification and peak review are adopted to the high-throughput environment and tested against a standard HPLC-ESI technology

Involvement of secondary metabolites in the pathogenesis of the American foulbrood of honey bees caused by Paenibacillus larvae

Covering: 2011 to end of 2014 The Gram-positive, spore-forming bacterium Paenibacillus larvae (P. larvae) is the causative agent of the epizootic American Foulbrood (AFB), a fatal brood disease of the western honey bee (Apis mellifera). AFB is one of the most destructive honey bee diseases since it is not only lethal for infected larvae but also for the diseased colonies. Due to the high impact of honey bees on ecology and economy this epizootic is a severe and pressing problem. Knowledge about virulence mechanisms and the underlying molecular mechanisms remain largely elusive. Recent genome sequencing of P. larvae revealed its potential to produce unknown secondary metabolites, like nonribosomal peptides and peptide-polyketide hybrids. This article highlights recent findings on secondary metabolites synthesized by P. larvae and discusses their role in virulence and pathogenicity towards the bee larvae

Fungal cyclooligomer depsipeptides: From classical biochemistry to combinatorial biosynthesis

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.This review surveys the biological activities and the iterative and recursive biosynthetic mechanisms of fungal cyclooligomer depsipeptides, and their structural diversification by various combinatorial biosynthetic methods