The pan-European order at the crossroads: three principles for a new beginning

The year 2014 confronted European policy-makers with a qualitatively altered situation. For the first time in many years an interstate conflict in Europe - manifested as an inner-state conflict - is being resolved by military means. Persistent uncertainty and a growing potential for conflict are the new realities the European Union (EU) must face - in its eastern neighborhood as well as in the Mediterranean region. This neighborhood also holds major strategic significance for the supply of energy to Europe. In order to limit the risks, it is necessary to define and construct a new pan-European order - based on existing conditions - that can rein in the potential for conflict, ensure greater predictability and build new trust. Germany should use its OSCE chairmanship in 2016 to initiate negotiations to this effect along the lines of new principles, with a view to establishing a pan-European order with a strong energy component as its core. (author's abstract

In Vitro and In Vivo Toxicometabolomics of the Synthetic Cathinone PCYP Studied by Means of LC-HRMS/MS

Synthetic cathinones are one important group amongst new psychoactive substances (NPS) and limited information is available regarding their toxicokinetics and -dynamics. Over the past few years, nontargeted toxicometabolomics has been increasingly used to study compound-related effects of NPS to identify important exogenous and endogenous biomarkers. In this study, the effects of the synthetic cathinone PCYP (2-cyclohexyl-1-phenyl-2-(1-pyrrolidinyl)-ethanone) on in vitro and in vivo metabolomes were investigated. Pooled human-liver microsomes and blood and urine of male Wistar rats were used to generate in vitro and in vivo data, respectively. Samples were analyzed by liquid chromatography and high-resolution mass spectrometry using an untargeted metabolomics workflow. Statistical evaluation was performed using univariate and multivariate statistics. In total, sixteen phase I and one phase II metabolite of PCYP could be identified as exogenous biomarkers. Five endogenous biomarkers (e.g., adenosine and metabolites of tryptophan metabolism) related to PCYP intake could be identified in rat samples. The present data on the exogenous biomarker of PCYP are crucial for setting up analytical screening procedures. The data on the endogenous biomarker are important for further studies to better understand the physiological changes associated with cathinone abuse but may also serve in the future as additional markers for an intake

Going deeper into the toxicokinetics of synthetic cannabinoids: in vitro contribution of human carboxylesterases

Synthetic cannabinoids (SC) are new psychoactive substances known to cause intoxications and fatalities. One reason may be the limited data available concerning the toxicokinetics of SC, but toxicity mechanisms are insufficiently understood so far. Human carboxylesterases (hCES) are widely known to play a crucial role in the catalytic hydrolysis of drugs (of abuse). The aim of this study was to investigate the in vitro contribution of hCES to the metabolism of the 13 SC 3,5-AB-5F-FUPPYCA, AB-5F-P7AICA, A-CHMINACA, DMBA-CHMINACA, MBA-CHMINACA, MDMB-4F-BINACA, MDMB-4en-PINACA, MDMB-FUBICA, MDMB-5F-PICA, MMB-CHMICA, MMB-4en-PICA, MMB-FUBINACA, and MPhP-5F-PICA. The SC were incubated with recombinant hCES1b, hCES1c, or hCES2 and analyzed by liquid chromatography–ion trap mass spectrometry to assess amide or ester hydrolysis in an initial activity screening. Enzyme kinetic studies were performed if sufficient hydrolysis was observed. No hydrolysis of the amide linker was observed using those experimental conditions. Except for MDMB-5F-PICA, ester hydrolysis was always detected if an ester group was present in the head group. In general, SC with a terminal ester bearing a small alcohol part and a larger acyl part showed higher affinity to hCES1 isozymes. Due to the low hydrolysis rates, enzyme kinetics could not be modeled for the SC with a tert-leucine-derived moiety, but hydrolysis reactions of MPhP-5F-PICA and of those containing a valine-derived moiety followed classic Michaelis–Menten kinetics. In conclusion, drug–drug/drug–food interactions or hCES polymorphisms may prolong the half-life of SC and the current results help to estimate the risk of toxicity in the future after combining them with activity and clinical data

Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data

The evaluation of liquid chromatography high-resolution mass spectrometry (LC-HRMS) raw data is a crucial step in untargeted metabolomics studies to minimize false positive findings. A variety of commercial or open source software solutions are available for such data processing. This study aims to compare three different data processing workflows (Compound Discoverer 3.1, XCMS Online combined with MetaboAnalyst 4.0, and a manually programmed tool using R) to investigate LC-HRMS data of an untargeted metabolomics study. Simple but highly standardized datasets for evaluation were prepared by incubating pHLM (pooled human liver microsomes) with the synthetic cannabinoid A-CHMINACA. LC-HRMS analysis was performed using normaland reversed-phase chromatography followed by full scan MS in positive and negative mode. MS/MS spectra of significant features were subsequently recorded in a separate run. The outcome of each workflow was evaluated by its number of significant features, peak shape quality, and the results of the multivariate statistics. Compound Discoverer as an all-in-one solution is characterized by its ease of use and seems, therefore, suitable for simple and small metabolomic studies. The two open source solutions allowed extensive customization but particularly, in the case of R, made advanced programming skills necessary. Nevertheless, both provided high flexibility and may be suitable for more complex studies and questions

Addendum: Hemmer, S., et al. Comparison of Three Untargeted Data Processing Workflows for Evaluating LC-HRMS Metabolomics Data. Metabolites 2020, 10, 378

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Die gesamteuropäische Ordnung vor einer Zäsur: drei Leitlinien für einen Neubeginn

Das Jahr 2014 hat die europäische Politik mit einer qualitativ veränderten Situation konfrontiert. In Europa wird erstmals seit langer Zeit wieder ein zwischenstaatlicher Konflikt – als innerstaatlicher Konflikt überformt – militärisch ausgetragen. Anhaltende Unsicherheit und wachsende Konfliktpotentiale sind die neuen Realitäten, denen sich die Europäische Union (EU) stellen muss – im angrenzenden Osten wie im Mittelmeerraum. Dieser geographische Raum ist auch für die Energieversorgung Europas von strategischer Bedeutung. Um die Risiken zu begrenzen, bedarf es der Bestimmung und des schrittweisen Aufbaus einer neuen gesamteuropäischen Ordnung, die – ausgehend von den bestehenden Gegebenheiten – Konfliktpotentiale einhegt, für größere Berechenbarkeit sorgt und neues Vertrauen schafft. Verhandlungen darüber sollte der deutsche OSZE-Vorsitz im Jahr 2016 entlang neuer Leitlinien initiieren und auf eine gesamteuropäische Ordnung mit einer starken Energie-Komponente als Keimzelle zielen. (Autorenreferat

Effects of heat shocks on biofilm formation and the influence on corrosion and scaling in a geothermal plant in the North German Basin

At geothermal plants, process failures often occur due to corrosion and scaling processes. Especially after heat extraction, sulfate reducing bacteria contribute to corrosion processes by producing reduced sulfur compounds. In biofilms containing scales such as iron sulfides, corrosion processes are enhanced. In a mobile bypass system located at the geothermal plant in Neubrandenburg (North German Basin), the influence of biofilm formation on corrosion and scaling was investigated. Short-term heat shocks were successfully tested in the bypass system in order to reduce biofilm formation and thus to diminish corrosion and scaling processes

Influence of microbial processes on the operational reliability in a geothermal heat store : results of long-term monitoring at a full scale plant and first studies in a bypass system

This paper describes microbial metabolic processes that are considered to be relevant for the technical reliability of a geothermal heat store. The study reports on changes of the microbial community composition in geothermal well fluids of different temperatures and after plant downtimes monitored by genetic fingerprinting. Stagnant conditions favored the enrichment of bacteria, sulfate reducers (SRB), and sulfur oxidizers (SOB) in the well. Furthermore higher concentrations of DOC, SO_4_2-, H_2S, and H_2 were detected in the first fluids produced after plant downtime. The increased abundance of SOB indicated oxygen ingress during plant downtime. The interaction of SRB and SOB might have further enhanced corrosion and scaling processes. A mobile bypass system installed at the site will help to understand the processes occurring in the well and to study biofilm formation and corrosion rates at different temperatures