Open Access

Many intrastate conflicts see more than one mediation effort. As the sequencing of mediation efforts in intrastate conflicts is neglected in existing research, this project addresses the question how and why previous mediation outcomes have an impact on subsequent mediation onset and subsequent mediation success. Drawing on bargaining theory, it is argued that governments and rebel groups engaged in intrastate conflicts account for previous mediation outcomes in their cost-benefit calculations on subsequent mediation onset, and, should subsequent talks set on, their behaviour during subsequent mediation efforts, which influences subsequent mediation success. If mediation did not produce an agreement, the persistence of the private information problem is noted by the conflict parties. Yet, no new costs of mediation are uncovered, and hence the conflict parties will agree to subsequent mediation onset. Being aware of the necessity to overcome the private information and the commitment problem, the mediator will seek to account for the concerns of the conflict parties, and thereby work towards subsequent mediation success. If mediation produced a partial agreement, the benefits of mediation are underlined. The private information and the commitment problem seem solved with the assistance of the mediator. Subsequent mediation onset and eventually subsequent mediation success are observed. If a mediated agreement was reneged on by the rebel group, the government will refrain from further talks, pointing out the rebel group’s illegitimacy. If the government reneged on the agreement itself, it will also decide against subsequent mediation, as the previous mediation effort produced an agreement which did not mirror the power distribution in the dyad. Costs of mediation, which outweigh the benefits of it, were highlighted. Rebel groups will opt for mediation regardless which side reneged on an agreement. As both governments and rebel groups have to agree to subsequent mediation for talks to set on, subsequent mediation onset is unlikely if a mediated agreement was reneged on. Given the onset of subsequent mediation after a mediated agreement was reneged on, subsequent mediation success is unlikely to be observed, due to the previously underlined hazards of sharing private information and the persistence of the commitment problem. The theoretical argument is tested with a mixed-methods approach. The quantitative analysis accounts for mediation efforts in African intrastate conflicts between 1993 and 2007. The qualitative analysis scrutinises the mediation efforts between the Government of Uganda and the Lord’s Resistance Army. The results of both parts of analysis largely go hand-in-hand, and show that partial mediation success and mediation which did not produce an agreement have a positive impact on subsequent mediation onset in particular, but also on subsequent mediation success. Reneged on mediated agreements have a severe negative impact on subsequent mediation onset and subsequent mediation success though. By addressing the question which impact previous mediation outcomes have on subsequent mediation efforts, this research shows that mediation which does not produce an agreement is not the mediation outcome which needs to be feared by the international community. Instead, the deteriorating impact of short-lived agreements, a mediation outcome which is unaccounted for in existing research as an explanatory variable, becomes apparent. This research has important policy implications, especially for mediators, as it suggests that accepting mediation efforts to end without an agreement is more conducive for subsequent mediation efforts. Moreover, this research points towards the necessity of including reneged on agreements in mediation research as an explanatory variable more extensively, thereby shedding more light onto the dynamics at play in consecutive mediation efforts.

Neu isolierte und synthetisierte Wirkstoffe müssen neben ihrer biologischen Wirksamkeit auch auf ihre Unbedenklichkeit für den Menschen hin untersucht werden. Ein Bestandteil der Untersuchungen zur Unbedenklichkeit ist die Prüfung auf mögliche Immuntoxizität. Die Risikobewertung und -klassifizierung von (immun-)toxischen Substanzen erfolgt derzeit in Tierversuchen, die, abgesehen von ethischen Bedenken, zeit- und kostenintensiv sind und deren Übertragbarkeit auf den Menschen nicht vollständig gewährleistet ist. Im Fokus dieser Arbeit stand die Etablierung und Anwendung eines Methodensets basierend auf funktionalen in vitro Methoden zur Charakterisierung immunologischer Wirkungen ausgewählter Naturstoffe. Dieses sollte der Beurteilung der immuntoxischen Wirkungen der getesteten Naturstoffe und der Entwicklung eines Entscheidungsbaums, der die Vorhersage des immuntoxischen Potentials mithilfe von in vitro Versuchen gestattet, dienen. Dazu wurden zwei humane Immunzelllinien (Jurkat-Zellen als Beispiel für T-Zellen, THP-1-Zellen als Beispiel für Monozyten) und für einige Versuche vergleichsweise primäre Blutzellen eingesetzt. Es wurden Methoden zur Untersuchung folgender Parameter etabliert und angewendet: Vitalität, Zellzyklusverteilung, Induktion von Apoptose, iROS, DNA-Schäden (Genotoxizität), Zytokinfreisetzung und mitochondriale Funktion. Folgende Naturstoffe wurden für die Untersuchungen ausgewählt: Mannitol und Urethan als Negativkontrollen, Cyclosporin A, Deoxynivalenol und Mycophenolsäure als Positivkontrollen, ausgehend von Hinweisen auf Wirkungen im Immunsystem Tulipalin A, Helenalin, Vincristin, Cannabidiol, Agaritin und p-Tolylhydrazin als Testsubstanzen. Es zeigten sich nur geringfügige Unterschiede der Substanzwirkungen zwischen den Immunzelllinien, welche v.a. auf Zytokinebene nachweisbar waren. Die Substanzen besaßen zeit- und konzentrationsabhängige Effekte. Die Negativkontrolle Mannitol hatte eine geringe Wirkung auf die Immunzelllinien, während Urethan die Zytokinfreisetzung supprimierte/¬stimulierte. Die untersuchten Positivkontrollen zeigten einen Einfluss auf die Zytokinfreisetzung und führten weiterhin zu immuntoxischen Effekten durch eine konzentrationsabhängige Apoptoseinduktion. Die Testsubstanzen Vincristin, Agaritin und p-Tolylhydrazin besaßen nur eine geringe toxische Wirkung auf die Immunzellen. Weitere Substanzen wie Cannabidiol, Helenalin und Tulipalin A wiesen immunspezifisch und - unspezifisch vermittelte Immuntoxizität durch einen Einfluss auf die Zytokinfreisetzung, Apoptose und iROS auf. Funktionale in vitro Untersuchungen zur Vitalität, Zellzyklusverteilung, Apoptose und Zytokinfreisetzung waren zum Nachweis bzw. Ausschluss von Immuntoxizität geeignet und neben Proteom- und Metabolomanalysen wesentlicher Bestandteil eines Entscheidungsbaums zur Klassifizierung von direkt immuntoxischen Substanzen. Es zeigte sich, dass die Zytokinmessung der wichtigste Parameter zur Klassifizierung von immuntoxischen Substanzen im subtoxischen Bereich ist. Es konnte sowohl Cyclosporin A als Positivkontrolle als auch Mannitol als Negativkontrolle in beiden Zelllinien bestätigt werden. Von den hinreichend untersuchten Testsubstanzen wurde Cannabidiol, Helenalin und Tulipalin A in Jurkat-Zellen sowie Cannabidiol und Tulipalin A in THP-1-Zellen unter Verwendung des Entscheidungsbaums als immuntoxisch klassifiziert. Darüber hinaus konnte die hautsensibilisierende Wirkung von Farnesol und Tulipalin A durch Anwendung von weiteren in vitro Methoden bestätigt werden. Eine Validierung der Ergebnisse mit weiteren bekannten immuntoxischen und nicht-immuntoxischen Substanzen würde eine Anwendung als Vorscreening Testung neuer Substanzen ermöglichen und nicht nur zu einer Reduktion von Tierversuchen führen, sondern auch eine Zeit- und Kostenersparnis bedeuten.

Humanity is constantly confronted with the emergence and reemergence of infectious diseases. Many of them produce large or devastating epidemics, like AIDS (HIV) and Ebola. Others have been long neglected, yet pose immediate threats to global public health as evidences the abrupt emergence of Zika virus in South America and its association with microcephaly in babies. The examples illustrate, that many of these diseases are provoked by RNA viruses. One of the first steps in understanding and eliminating those threats is the development of sensitive and rapid diagnostic methods. A general and relatively rapid method is the direct detection and examination of the agent’s genome. However, the nature of (re)emerging RNA viruses poses a series of very specific problems for the design of such methods. Therefore, a systematic approach was proposed for the design of DNA-hybridization-base methods to detect and characterize RNA viruses that will have both a high sensitivity and a specificity sufficiently broad to detect, per reaction, down to a single copy of any of the possible variants of the viral genome. Following this approach a series of assays were designed, developed or adapted and put into use for detection and characterization of important RNA viruses. One of those viruses is West Nile virus (WNV), which after its explosive introduction into USA become the most widespread flavivirus throughout the world and, consequently, many countries began an intensive monitoring. While existing assay detected predominantly the Lineage 1, in Europa Lineage 2 was expected. Two new RT-qPCR for the detection of both lineages were developed, and reportedly used by independent laboratories. Due to more than 50000 associated deaths per year, the Hepatitis E virus also received an increasing attention to elucidate novel routes of transmission. This virus (especially genotype 3) has the zoonotic potential of transmission from pigs and wild boar to humans. RT-qPCR and nested qPCR for detection and characterization of this virus as well as a methodology for subtyping were developed and the first detected case of subtype 3b in a German wild animal was documented. In addition a novel assay for flaviviruses conformed by a RT-qPCR coupled with a low density DNA microarray was developed, which enabled the identification of WNV in mosquitoes from Greece. A RT-qPCR suitable for surveillance and diagnostic of all known variants of Venezuelan equine encephalitis virus was developed too. A causative agent of hemorrhagic infections, the Ngari virus, was detected and characterized in animal samples from Mauritania. These achievements were supported by the development of software applications for selection and visualization of primers and probes from aligned DNA sequences and for modeling of DNA hybridizations using unaligned sequences. In conclusion a general methodology for rapid development of sensitive diagnostic methods based in DNA-hybridization technics (PCR, sequencing and microarray) was stablished and successful applications are reported.

Rabies virus (RABV) is an ancient, highly neurotropic rhabdovirus that causes lethal encephalitis. Most RABV pathogenesis determinants have been identified with laboratory-adapted or attenuated RABVs, but details of natural RABV pathogenesis and attenuation mechanisms are still poorly understood. To provide a deeper insight in the cellular mechanism of pathogenies of field RABV, this work was performed to assess virus strain specific differences in intra-neuronal virus transport, to identify cell culture adaptive mutations in recombinant field viruses and to explore shRNA-expressing RABVs as research tools for targeted host manipulation in infected cells. Comparison of chimeric RABVs with glycoprotein (G) ecto-domains of different lyssaviruses, together with field RABVs from dog and fox in dorsal root ganglion (DRG) neurons revealed no detectable differences in the axonal accumulation of the viruses. This indicates that previously described G-dependent transport of newly formed RABV in axons can occur both in laboratory-adapted and field RABV. Moreover, partial overlap of nucleoprotein (N) and G protein particles in field virus infected DRG axons supported the hypothesis of the “separate model” for anterograde RABV transport. Serial passages of recombinant dog and fox field clones in different cell lines led to the identification of general (D266N) and cell line specific (K444N) adaptive mutations in the G ecto-domain of both viruses. In BHK cells, synergistic effects of D226N, K444N and A417T on field dog virus G protein surface localization led to the loss of endoplasmic reticulum (ER) retention of G and increased virus titers in the supernatant, indicating that limited virus release by ER retention is a major bottleneck in cell culture adaptation. In addition, selection of mutations within the C-terminus of the RABV phosphoprotein (P) (R293H and R293C in fox and dog viruses, respectively) led to the hypothesis of altered binding affinities to nucleoprotein and RNP complexes. Identification of the above mentioned amino acid substitutions together with alterations in a suboptimal transcription stop signal in the P/M gene border indicated that adaptation to cell culture replication occurs on both levels, RNA transcription/replication and virus release. To evaluate the possibility of an expression of a functional microRNA-adapted short-hairpin RNAs (miR-shRNA) expressing RABV, recombinant RABVs encoding miR-shRNAs against cellular Dynein Light Chain 1 (DYNLL1) and Acidic Nuclear Phosphoprotein 32 family member B (ANP32B) were generated. In spite of cytoplasmic transcription of the respective mRNAs, downregulation of DYNLL1 and ANP32B mRNA and respective protein levels in infected cells revealed correct processing to functional shRNAs. Specific downregulation of the cellular genes at 2, 3 and 4 days post infection further demonstrated feasibility of the approach in standard cell lines. However, it remained open whether miR-shRNA expressing RABV can be used to study neuro-infection in vivo. Since first attempts in primary rat neuron cultures failed, it has to be clarified in further experiments whether this strategy can be used in mature, non-dividing neurons or whether breakdown of the nucleus in the course of cell division is a requirement for the processing of cytoplasmically expressed miR-RNA by nuclear RNases. By providing novel insights in axonal RABV transport and cell culture adaptive mutations this work extends the current understanding of RABV pathogenesis in natural and non-natural cell environments. Moreover, it provides a basis for further pathogenicity studies in which the impact of cell culture adaptation through increased virus release on RABV virulence can be investigated. With successful expression of functional miR-shRNAs from RABV vectors, this work also provides a tool for RABV gene targeting in infected cell lines and thus may contribute to the further investigation of RABV-host-cell-interactions.

Bacteria are exposed to oxidative stress as an unavoidable consequence of their aerobic lifestyle. Reactive oxygen species (ROS) are generated in the stepwise one-electron reduction of molecular oxygen during the respiration. Pathogens encounter ROS during the oxidative burst of macrophages as part of the host immune defense. Besides ROS, bacteria also have to cope with reactive chlorine, electrophilic and nitrogen species (RCS, RES, RNS). To cope with these reactive species, bacteria have evolved different defense and repair mechanisms. To maintain the reduced state of the cytoplasm, they utilize low molecular weight (LMW) thiols. LMW thiols are small thiol-containing compounds that can undergo post-translational thiolmodifications with protein thiols, termed as S-thiolations. S-thiolations function as major redox regulatory and thiol-protection mechanism under oxidative stress conditions. In eukaryotes and Gram-negative bacteria, the tripeptide glutathione (GSH) functions as major LMW thiol, which is present in millimolar concentrations. The Actinomycetes, such as Mycobacterium and Corynebacterium species do not produce GSH and utilize instead mycothiol (MSH) as their alternative LMW thiol. In Firmicutes, including Bacillus and Staphylococcus species, bacillithiol (BSH) functions as the major LMW thiol. LMW thiols protect protein thiols against the irreversible overoxidation of cystein residues to sulfinic and sulfonic acids. In addition, LMW thiols contribute to the virulence and survival of pathogens, function in metal homeostasis and serve as enzyme cofactors for detoxification of xenobiotics and antibiotics. In this doctoral thesis, we aimed to investigate the roles of MSH and BSH in redox regulation of main metabolic enzymes under oxidative stress in the pathogens Corynebacterium diphtheriae and Staphylococcus aureus. Previous redox proteomics studies identified the glyceraldehyde-3-phosphate dehydrogenase GapDH and the aldehyde dehydrogenase AldA as S-thiolated in S. aureus and C. diphtheriae. Thus, we aimed to study the redox regulation of the metabolic enzyme GapDH in C. diphtheriae in response to NaOCl and H2O2 stress by S-mycothiolation, which is described in chapter 1. Moreover, we studied the involvement of the mycoredoxin-1 (Mrx1) and thioredoxin (Trx) pathways in reactivation of S-mycothiolated GapDH in vitro. Using shotgun proteomics, 26 S-mycothiolated proteins were identified under NaOCl stress in C. diphtheriae. These are involved in energy metabolism (Ndh, GlpD) and in the biosynthesis of amino acids (ThrA, LeuB), purines (PurA) and cell wall metabolites (GlmS). The glycolytic GapDH was identified as conserved target for S-thiolation across Gram-positive bacteria. GapDH was the most abundant protein, contributing with 0.75 % to the total cystein proteome. Moreover, GapDH is a conserved target for redox regulation and S-glutathionylation in response to oxidative stress in several prokaryotic and eukaryotic organisms. Treatment of GapDH with NaOCl and H2O2 in the absence of MSH resulted in irreversible enzyme inactivation due to overoxidation. Pretreatment of GapDH with MSH prior to H2O2 or NaOCl exposure resulted in reversible inactivation due to S-mycothiolation of the active site Cys153. Since S-mycothiolation is faster compared to overoxidation, S-mycothiolation efficiently protects the GapDH active site against overoxidation. The activity of S-mycothiolated GapDH could be restored by both, the Mrx1 and Trx pathway in vitro. Interestingly, the recovery of Smycothiolated GapDH by Mrx1 was faster compared to its reduction by the Trx pathway. In previous studies, the reactivation of S-mycothiolated Mpx and MrsA by the mycoredoxin pathway occurred also faster compared to the Trx pathway, which is consistent with our results. We were further interested to analyze the redox regulation of the glyceraldehyde-3phosphate dehydrogenase Gap of S. aureus under NaOCl and H2O2 stress, which is described in chapter 2. Using the quantitative redox proteomic approach OxICAT, 58 NaOCl-sensitive cystein residues with >10% thiol oxidation under NaOCl stress were identified. Gap and AldA showed the highest oxidation increase of 29% under NaOCl stress at their active site cystein residues. Using shotgun proteomics, five S-bacillithiolated proteins were identified, including Gap, AldA, GuaB, RpmJ and PpaC. Gap contributed with 4 % as most abundant cystein protein to the total cystein proteome. Our activity assays demonstrated that Gap of S. aureus is highly sensitive to overoxidation by H2O2 and NaOCl in vitro in the absence of BSH. The active site Cys151 of Gap was oxidized to the BSH mixed disulfide under H2O2 and NaOCl stress in the presence of BSH in vitro, which resulted in the reversible Gap inactivation. Moreover, inactivation of Gap by NaOCl and H2O2 due to S-bacillithiolation was faster compared to overoxidation, indicating that S-bacillithiolation protects the Gap active site against overoxidation in vitro. We further showed that the bacilliredoxin Brx catalyzes the reduction of S-bacillithiolated Gap in vitro. Molecular docking of BSH into the Gap active site revealed that S-bacillithiolation does not require major structural changes. Apart from Gap, the aldehyde dehydrogenase AldA was identified as S-bacillithiolated at its active site Cys279 under NaOCl stress in S. aureus previously. Thus, the expression, function, redox regulation and structural changes of AldA were analysed under NaOCl and aldehyde stress in S. aureus as summarized in chapter 3. AldA was S-bacillithiolated in the presence of H2O2 and BSH as demonstrated in BSH-specific Western blots in vitro. The expression of aldA was previously shown to be regulated by the alternative sigma factor SigmaB in S. aureus. Transcription of aldA was strongly increased in a SigmaB-independent manner under formaldehyde, NaOCl and diamide stress in S. aureus. Using an aldA deletion mutant, we demonstrated that aldA is required for growth and survival under NaOCl stress in S. aureus. The purified AldA enzyme was shown to catalyze the oxidation of various aldehyde substrates, including formaldehyde, methylglyoxal, glycolaldehyde and acetaldehyde in vitro. In addition, the function of the conserved Cys279 for AldA activity was investigated in vivo and in vitro. The purified AldAC279S mutant was shown to be inactive for aldehyde oxidation in vitro. Moreover, the aldAC279S mutant was very sensitive under NaOCl stress in vivo, and this phenotype could be reversed using the aldA complemented strain. These experiments demonstrate the function of Cys279 for AldA activity both in vitro and in vivo. AldA activity assays showed that AldA is sensitive to overoxidation and irreversible inactivation by H2O2 alone in vitro. In the presence of BSH, AldA is protected against overoxidation by reversible Sbacillithiolation in vitro. Molecular docking and molecular dynamics simulations revealed that BSH occupies two different positions in the Cys279 active site, which depend on the NAD+ cofactor. In the apoenzyme, BSH forms the disulfide with Cys279 in the “resting” state position, while Cys279 is S-bacillithiolated in the “attacking” state position in the holoenzyme in the presence of the NAD+ cofactor.

Background: The high incidence of methicillin-resistant Staphylococcus aureus (MRSA) strengthens the need for new effective antibiotics and a protective vaccine. Up till now, mainly human-adapted Staphylococcus aureus strains were used to study S. aureus pathogenicity in mouse models. However, it is known that S. aureus is highly host-specific. Recently, a mouse-adapted S. aureus strain, JSNZ, was identified. This strain could be a promising tool in developing more appropriate infection models. JSNZ produces high amounts of a putative extracellular protease, named JSNZ extracellular protease (Jep). Since the jep gene was only detected in S. aureus isolates from laboratory mice and wild small rodents and shrews, we hypothesize that Jep is important for colonization and infection in mice. The jep deletion mutant previously created by our collaborators from the University of Auckland, New Zealand, intriguingly showed a reduced survival and growth fitness in murine serum and whole blood as compared to the JSNZ wild type (WT) strain. Objective: To elucidate the role of Jep in the interaction between S. aureus and its host by comparing the impact of JSNZ WT with a mutant and a complement strain on the murine immune system. In addition, the elucidation of possible genetic factors behind host-adaptation of S. aureus strains isolated from wild rodents and shrews. Methods: A jep complemented strain was generated by chromosomal replacement. JSNZ WT, the jep mutant and the complement strain were subjected to functional assays (whole blood survival assay, coagulation assay). In addition, the genetic background that might confer host specificity was tested by staph array genotyping. Results: The mutant strain JSNZDjep was successfully complemented with the jep gene using a chromosomal integration approach. The WT strain and the complemented strain produced the Jep protein in comparable amounts. Unexpectedly, the complemented strains did not behave like the WT strain but rather like the mutant in a series of in vitro assays. Firstly, the growth of both the deletion mutant and the complemented strains was slightly reduced in TSB as compared to the WT strain. Secondly, the jep knockout strain showed a strongly reduced survival in murine whole blood compared to its wild type counterpart, but so did the complemented strain. Finally, the coagulation of murine plasma was less pronounced for the jep deletion mutant and the complemented strain as compared to the JSNZ WT. To exclude a defect in jep gene expression, we compared the amount of Jep expressed during growth in TSB medium for the three strains. The complemented strain produced Jep in a manner similar to the WT strain in a growth-phase dependent manner, suggesting that Jep expression was not affected during the creation of the complemented strain. The array data showed some differences in the genetic makeup between animal isolated strains and matched human strains. For example, while all animal isolates of the CC88 lacked the resistance mecA gene it was found in some human isolates of the same strain. Conclusion: In conclusion, our unidentified mutation created during the generation of the jep knock-out strain rather than the jep gene itself manipulated the murine immune response. The responsible gene and the underlying mechanisms remain to be clarified. Genetic profiling of S. aureus strains allowed us to obtain some valuable information including data about CC49, the most frequently isolated lineage in wild rodents and shrews where compared to the human isolates the murine strains showed clear signs of host adaptation. However, the analysis had several limitations including the small sample size.

Amine transaminases are versatile biocatalysts for the production of pharmaceutically and agrochemically relevant chiral amines. They represent an environmentally benign alternative to waste intensive transition metal catalysed synthesis strategies, especially because of their high stereoselectivity and robustness. Therefore, they have been frequently used in the (chemo)enzymatic synthesis of amines and/or became attractive targets for enzyme engineering especially in the last decade, mainly in order to enlarge their substrate scope. Certainly, one of the most notable examples of amine transaminase engineering is the manufacturing of the anti-diabetic drug Sitagliptin in large scale after several rounds of protein engineering. Thereby, the target amine was produced in asymmetric synthesis mode which is the most convenient and favored route to a target chiral amine, starting from the corresponding ketone. The choice of the amine donor is highly relevant for reaction design in terms of economical and thermodynamic considerations. For instance, the use of alanine as the natural amine donor is one of the most common strategies for the amination of target ketones but needs the involvement of auxiliary enzymes to shift the reaction equilibrium towards product formation. In fact, isopropylamine is probably one of the most favored donor molecules since it is cheap and achiral but it is supposed to be accepted only by a limited number of amine transaminases. This thesis focusses on the optimization and application of amine transaminases for asymmetric synthesis reactions en route to novel target chiral amines using isopropylamine as the preferred amine donor.

Zusammenfassung Der Iran besitzt zwölf UNESCO-Biosphärenreservate, die reich an einmaligen Natur- und Kulturschätzen und hohem menschlichen Potenzial aus verschiedenen ethnischen Gruppen sind. Die ersten neun Biosphärenreservate wurden frühzeitig mit den ersten Biosphärenreser-vaten der Welt im Jahr 1976 gegründet, die auch gleichzeitig andere Kategorien der Schutz-gebiete im Iran wie Nationalparks, geschützte Lebensräume für Wildtiere und Naturschutzge-biete beinhalten und bis heute unter ihrem alten Status verwaltet werden. Damit entsprechen sie nicht den aktuellen internationalen Anforderungen an Biosphärenreservate und besteht die Gefahr, dass diese Gebiete in baldiger Zukunft ihre natürlichen und kulturellen Werte verlie-ren und irreversibel beschädigt werden. Diese Studie untersucht und bewertet die zwei exemplarisch ausgewählten iranischen Bio-sphärenreservate Golestan und Dena unter Berücksichtigung der UNESCO-Kriterien, unter anderem die Ziele und Grundlagen der Sevilla-Strategie und der Internationalen Leitlinien für das Weltnetz der Biosphärenreservate (1995). Das Biosphärenreservat Golestan wurde im Jahr 1976 gegründet und ist somit eines der ältesten Biosphärenreservate des Irans. Bei dem im Jahre 2010 gegründeten Biosphärenreservat Dena, handelt es sich um das jüngste Biosphä-renreservat im Iran zu Beginn der Studie. Beide Schutzgebiete sind gebirgig und beinhalten die wichtigsten Waldökosysteme mit einer großen Biodiversität. Das Biosphärenreservat Golestan befindet sich im Nordosten des Irans im östlichsten Teil des Elburs-Gebirge und Dena liegt im zentralen Zagros-Gebirge im Westiran. Für den methodischen Ansatz dieser Studie wurde ein Methodenmix aus qualitativen Elemen-ten: Oral History, Interviews, offenen Fragen und Teilnehmender Beobachtung und quantita-tiven Elementen: SWOT-Analyse (engl. Akronym für Strengths (Stärken), Weaknesses (Schwächen), Opportunities (Chancen) und Threats (Bedrohungen) und Auswertung der Fra-gebögen mit Hilfe des statistischen Programms SPSS20 angewendet. Die untersuchten Gruppen bestanden gemäß der jeweiligen Analyse aus Experten des De-partments für Umwelt (DoE) in Teheran, den Provinz-Umweltschutzbehörden von Golestan und Kohgiluye und Boyer Ahmad, Akademikern, der Nationale Commission for UNESCO in Teheran, Zeitzeugen, lokaler Bevölkerung, Rangern, Umwelt-NGOs (engl. Non-Governmental Organization), dem Tourismus-Sektor und den Umwelt-Medien. Die Ergebnisse in dieser Studie zeigen, dass die Entwicklung der iranischen Biosphärenreser-vate seit ihrer Gründung 1976 bis heute von den Veränderungen der wirtschaftlichen, politi-schen und gesellschaftlichen Situation des Irans und demzufolge von den Veränderungen in der Organisationsstruktur des Departemants für Umwelt (DoE) und der Prioritätensetzung in Bezug auf die Gesetze zu Umwelt- und Naturschutz beeinflusst wurden. Überdies stellen die Ergebnisse dar, dass in den beiden untersuchten Biosphärenreservaten Golestan und Dena hinsichtlich der internationalen UNESCO-Kriterien und Richtlinien ver-gleichsweise ähnliche Defizite und Mängel bestehen: • fehlende nationale Rechtsstruktur für die Biosphärenreservate im Iran, • fehlender Managementplan für Biosphärenreservate und somit auch schwaches Mana-gementsystem der Biosphärenreservate, • Mangel an Kenntnissen über Biosphärenreservate, • beschränkte Beteiligung an den Angelegenheiten der Biosphärenreservate seitens aller untersuchten Gruppen – von der lokalen Bevölkerung bis hin zu den staatlichen Ent-scheidungsträgern und • ungenügende Zusammenarbeit zwischen Staat und Interessengruppen in diesen Gebie-ten. Ebenso wurde in dieser Studie versucht, konkrete Lösungsansätze zur Verwirklichung der Ziele der Biosphärenreservate bzw. der Verbesserung ihrer aktuellen Situation zu empfehlen. In diesem Zusammenhang ist es erforderlich, dass Gesetze für die Biosphärenreservate auf nationaler Ebene definiert und die vorhandenen Biosphärenreservate im Iran gründlich nach internationalen Kriterien untersucht und mit einem systematischen Managementplan auf wis-senschaftlicher Grundlage verwaltet werden. Des Weiteren benötigen diese Gebiete für ihre Funktionalität eine Erhöhung und Verbesserung der Kenntnisse über die Biosphärenreservate der aktiven Personen, sowie der Kooperation und Kommunikation zwischen allen zuständigen Behörden und Interessengruppen. Hiermit soll allen sozialen, kulturellen, geistigen und wirt-schaftlichen Anliegen der Interessengruppen, vor allem aber der lokalen Bevölkerung, Rech-nung getragen werden, entsprechend dem weltweiten Ansatz der UNESCO-Biosphärenreservate.

Glacitectonic deformation in the Quaternary caused the tectonic framework of large-scale folds and displaced thrust sheets of Maastrichtian (Upper Cretaceous) chalk and Pleistocene glacial deposits in the southwestern Baltic Sea area. A wide spectrum of methods has been compiled to unravel the structural evolution of the Jasmund Glacitectonic Complex. The analyses of digital elevation models (DEM) suggest a division into two structural sub-complexes – a northern part with morphological ridges striking NW–SE and a southern part with SW–NE trending ridges. Geological cross sections from the eastern coast (southern sub-complex) were constructed and restored using the software Move™ and the complementary module 2D Kinematic Modelling™. The final geometric model of the southern sub-complex shows a small-scale fold-and-thrust belt. It includes three different orders of architectural surfaces (see PEDERSEN, 2014): erosional surfaces and the décollement (1st order), thrust faults (2nd order), and beds outlining hanging-wall anticlines as well as footwall synclines (3rd order). Thrust faults of the southern structural sub-complex are mainly inclined towards south, which indicates a local glacier push from the S/SE. The glacitectonic structures have a surface expression in form of sub-parallel ridges and elongated valleys in between. Geomorphological mapping and detailed landform analyses together with the structural investigations provide an insight into the chronology of sub-complexes formation. The northern part of the glacitectonic complex is suggested to have been formed before the southern one, considering the partly truncated northerly ridges and their superimposition by the southern sub-complex. Although there is a high number of scientific publications on the glacitectonic evolution of Jasmund, these presented models often lack a consistent theory for the development integrating all parts of the 100 km2 large complex. Therefore, the combination of all results leads to a more self-consistent genetic model for the entire Jasmund Glacitectonic Complex.

In dieser Arbeit wurden die Eigenschaften von atmosphärendruckplasmaaktivierten Natriumchloridlösungen (NaCl-Lösungen), unter Anwendung von nass-chemischen und mikrobiologischen Analysenverfahren, untersucht. Es zeigte sich, dass plasmaaktivierte NaCl-Lösungen sowohl mit kurzzeitigen als auch mit langzeitigen antimikrobiellen Effekten generiert werden können. Diese Effekte korrelieren mit einer Änderung der chemischen Zusammensetzung der flüssigen Phase. Molekularbiologische Untersuchungen zeigten, dass die antimikrobiellen Effekte auf unterschiedlichen Wirkmechanismen, vor allem auf oxidativem und nitrosativem Stress, beruhen. Anwendungsorientierte Untersuchungen haben gezeigt, dass plasmaaktivierte NaCl-Lösungen über ein enges Wirkspektrum (grampositive und gramnegative Erreger) verfügen, sich keine schnellen Resistenzen gegen den Testorganismus ausbilden und eine Kombination mit handelsüblichen Antibiotika ein vielversprechender Ansatz für eine Wirkungssteigerung der verwendeten Antibiotika ist.