TY - JOUR A1 - Sun, Ping A1 - Ortega, Gabriela A1 - Tan, Yan A1 - Hua, Qian A1 - Riederer, Peter F. A1 - Deckert, Jürgen A1 - Schmitt-Böhrer, Angelika G. T1 - Streptozotocin impairs proliferation and differentiation of adult hippocampal neural stem cells in vitro-correlation with alterations in the expression of proteins associated with the insulin system JF - Frontiers in Aging Neuroscience N2 - Rats intracerebroventricularily (icv) treated with streptozotocin (STZ), shown to generate an insulin resistant brain state, were used as an animal model for the sporadic form of Alzheimer's disease (sAD). Previously, we showed in an in vivo study that 3 months after STZ icv treatment hippocampal adult neurogenesis (AN) is impaired. In the present study, we examined the effects of STZ on isolated adult hippocampal neural stem cells (NSCs) using an in vitro approach. We revealed that 2.5 mM STZ inhibits the proliferation of NSCs as indicated by reduced number and size of neurospheres as well as by less BrdU-immunoreactive NSCs. Double immunofluorescence stainings of NSCs already being triggered to start with their differentiation showed that STZ primarily impairs the generation of new neurons, but not of astrocytes. For revealing mechanisms possibly involved in mediating STZ effects we analyzed expression levels of insulin/glucose system-related molecules such as the glucose transporter (GLUT) 1 and 3, the insulin receptor (IR) and the insulin-like growth factor (IGF) 1 receptor. Applying quantitative Real time-PCR (qRT-PCR) and immunofluorescence stainings we showed that STZ exerts its strongest effects on GLUT3 expression, as GLUT3 mRNA levels were found to be reduced in NSCs, and less GLUT3-immunoreactive NSCs as well as differentiating cells were detected after STZ treatment. These findings suggest that cultured NSCs are a good model for developing new strategies to treat nerve cell loss in AD and other degenerative disorders. KW - Alzheimer’s disease KW - streptozotocin KW - proliferation KW - neural stem cells KW - insulin-like growth factor 1 receptor KW - insulin receptor KW - glucose transporter KW - differentiation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176741 VL - 10 IS - 145 ER - TY - THES A1 - Bartossek, Thomas T1 - Structural and functional analysis of the trypanosomal variant surface glycoprotein using x-ray scattering techniques and fluorescence microscopy T1 - Strukturelle und funktionale Analyse des variablen Oberflächenproteins von Trypanosoma brucei mithilfe vön Röntgenstreutechniken und Fluoreszenzmikroskopie N2 - Trypanosoma brucei is an obligate parasite and causative agent of severe diseases affecting humans and livestock. The protist lives extracellularly in the bloodstream of the mammalian host, where it is prone to attacks by the host immune system. As a sophisticated means of defence against the immune response, the parasite’s surface is coated in a dense layer of the variant surface glycoprotein (VSG), that reduces identification of invariant epitopes on the cell surface by the immune system to levels that prevent host immunity. The VSG has to form a coat that is both dense and mobile, to shield invariant surface proteins from detection and to allow quick recycling of the protective coat during immune evasion. This coat effectively protects the parasite from the harsh environment that is the mammalian bloodstream and leads to a persistent parasitemia if the infection remains untreated. The available treatment against African Trypanosomiasis involves the use of drugs that are themselves severely toxic and that can lead to the death of the patient. Most of the drugs used as treatment were developed in the early-to-mid 20th century, and while developments continue, they still represent the best medical means to fight the parasite. The discovery of a fluorescent VSG gave rise to speculations about a potential interaction between the VSG coat and components of the surrounding medium, that could also lead to a new approach in the treatment of African Trypanosomiasis that involves the VSG coat. The initially observed fluorescence signal was specific for a combination of a VSG called VSG’Y’ and the triphenylmethane (TPM) dye phenol red. Exchanging this TPM to a bromo-derivative led to the observation of another fluorescence effect termed trypanicidal effect which killed the parasite independent of the expressed VSG and suggests a structurally conserved feature between VSGs that could function as a specific drug target against T. b. brucei. The work of this thesis aims to identify the mechanisms that govern the unique VSG’Y’ fluorescence and the trypanocidal effect. Fluorescence experiments and protein mutagenesis of VSG’Y’ as well as crystallographic trials with a range of different VSGs were utilized in the endeavour to identify the binding mechanisms between TPM compounds and VSGs, to find potentially conserved structural features between VSGs and to identify the working mechanisms of VSG fluorescence and the trypanocidal effect. These trials have the potential to lead to the formulation of highly specific drugs that target the parasites VSG coat. During the crystallographic trials of this thesis, the complete structure of a VSG was solved experimentally for the first time. This complete structure is a key component in furthering the understanding of the mechanisms governing VSG coat formation. X-ray scattering techniques, involving x-ray crystallography and small angle x-ray scattering were applied to elucidate the first complete VSG structures, which reveal high flexibility of the protein and supplies insight into the importance of this flexibility in the formation of a densely packed but highly mobile surface coat. N2 - Trypanosoma brucei ist ein eukaryotischer Parasit welcher bei Menschen und Nutztieren schwere Krankheiten auslöst. Der Protist lebt extrazellulär im Blutstrom seines Säugetier-Wirtes, in welchem er unter konstantem Angriff durch das Wirts-Immunsystem steht. Als ausgeklügelte Methode zur Umgehung der Immunantwort besitzt der Parasit einen dichten Oberflächenmantel des variablen Oberflächen-Glycoproteins (VSG), welcher die Identifikation invariabler Oberflächenproteine durch das Immunsystem erschwert und Wirts-Immunität gegen den Parasiten verhindert. Der gebildete VSG-Mantel muss gleichzeitig eine hohe Dichte besitzt, um invariable Oberflächenproteine vor Immundetektion zu beschützen, und eine hohe Mobilität aufweisen, um ein schnelles Recycling des Schutzmantels während Immunantworten zu gewährleisten. Dieser Mantel schützt den Parasiten effektiv vor dem Wirts-Immunsystem und führt bei fehlender Behandlung des Patienten zur persistenten Parasitemie durch Trypanosoma brucei. Die verfügbaren Behandlung gegen die Afrikanische Trypanosomiasis beinhaltet die Benutzung von Medikamenten welche ihrerseits z.T. stark toxisch sind und den Tod des Patienten verursachen können. Ein Großteil der verfügbaren Medikamente wurden zu Beginn des letzten Jahrhunderts entwickelt und stellen trotz anhaltenden Entwicklungen noch immer die beste Lösung im Kampf gegen den Parasiten dar. Die Entdeckung eines fluoreszierenden VSGs deutete auf eine Interaktionen zwischen dem VSG Mantel und Bestandteilen des umgebenden Medium hin, welche die Entwicklung von Medikamenten mit dem VSG Mantel als Drug Target ermöglichen könnte. Das ursprünglich beobachtete Fluoreszenz-Signal war spezifisch für eine Kombination eines VSG namens VSG’Y’ und dem Triphenylmethan (TPM) Phenolrot. Der Austausch von Phenolrot gegen ein Brom-Derivat führte zur Beobachtung eines weiteren Fluoreszenz-Effekts, welcher unabhängig vom exprimierten VSG auftritt und letal für den Parasiten ist. Dieser so genannten Trypanozide Effekt lässt auf konservierte Strukturen schließen, welche von allen VSGs geteilt werden und als hochspezifisches Drug Target gegen T. b. brucei fungieren könnten. Das Ziel der vorliegenden Arbeit war es, die Mechanismen zu identifizieren, welche die einzigartige VSG’Y’-Fluoreszenz und den Trypanoziden Effekt auslösen. Fluoreszenz-Experimente und Protein-Mutagenese von VSG’Y’, sowie röntgenkristallographische Analysen mit mehreren unterschiedlichen VSGs wurden in dem Bestreben durchgeführt, die Bindung zwischen VSGs und TPMs zu charakterisieren, potentiell konservierte Strukturen von VSGs zu finden und die Mechanismen der einzigartigen VSG’Y’-Fluoreszenz und des Trypanoziden Effekts zu identifizieren. Diese Arbeiten haben das Potenzial die Formulierung hochspezifischer Medikamente mit VSGs als Drug Target anzutreiben. Im Rahmen der kristallographischen Analysen wurden die ersten vollständigen VSG Strukturen ermittelt, welche eine hohe Bedeutung für das Verständnis über die Bildung des VSG-Mantels haben. Die VSG Strukturen wurden u.a. per Röntgenkristallographie und Kleinwinkel-Röntgenstreuung aufgeschlüsselt und zeigten dass VSGs ein hohes Maß an Flexibilität besitzen. Diese Flexibilität ist wichtig für die Bildung eines dichten und hochmobilen VSG-Mantels. KW - Trypanosoma brucei brucei KW - Röntgenstrukturanalyse KW - Röntgen-Kleinwinkelstreuung KW - Mutagenese KW - Fluoreszenzmikroskopie KW - Variables Oberflächen Glycoprotein KW - VSG Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144775 ER - TY - JOUR A1 - Dunce, James M. A1 - Milburn, Amy E. A1 - Gurusaran, Manickam A1 - da Cruz, Irene A1 - Sen, Lee T. A1 - Benavente, Ricardo A1 - Davies, Owen R. T1 - Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1 JF - Nature Communications N2 - Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate. KW - DNA KW - meiosis KW - proteins KW - super-resolution microscopy KW - X-ray crystallography Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226416 VL - 9 ER - TY - JOUR A1 - Hobbs, Christopher A1 - Jaskaniec, Sonia A1 - McCarthy, Eoin K. A1 - Downing, Clive A1 - Opelt, Konrad A1 - Güth, Konrad A1 - Shmeliov, Aleksey A1 - Mourad, Maurice C. D. A1 - Mandel, Karl A1 - Nicolosi, Valeria T1 - Structural transformation of layered double hydroxides: an in situ TEM analysis JF - npj 2D Materials and Applications N2 - A comprehensive nanoscale understanding of layered double hydroxide (LDH) thermal evolution is critical for their current and future applications as catalysts, flame retardants and oxygen evolution performers. In this report, we applied in situ transmission electron microscopy (TEM) to extensively characterise the thermal progressions of nickel-iron containing (Ni-Fe) LDH nanomaterials. The combinative approach of TEM and selected area electron diffraction (SAED) yielded both a morphological and crystallographic understanding of such processes. As the Ni-Fe LDH nanomaterials are heated in situ, an amorphization occurred at 250 °C, followed by a transition to a heterogeneous structure of NiO particles embedded throughout a NiFe2O4 matrix at 850 °C, confirmed by high-resolution TEM and scanning TEM. Further electron microscopy characterisation methodologies of energy-filtered TEM were utilised to directly observe these mechanistic behaviours in real time, showing an evolution and nucleation to an array of spherical NiO nanoparticles on the platelet surfaces. The versatility of this characterisation approach was verified by the analogous behaviours of Ni-Fe LDH materials heated ex situ as well as parallel in situ TEM and SAED comparisons to that of an akin magnesium-aluminium containing (Mg-Al) LDH structure. The in situ TEM work hereby discussed allows for a state-of-the-art understanding of the Ni-Fe material thermal evolution. This is an important first, which reveals pivotal information, especially when considering LDH applications as catalysts and flame retardants. KW - electrocatalysis KW - two-dimensional materials Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320752 VL - 2 ER - TY - JOUR A1 - Ribitsch, Iris A1 - Peham, Christian A1 - Ade, Nicole A1 - Duerr, Julia A1 - Handschuh, Stephan A1 - Schramel, Johannes Peter A1 - Vogl, Claus A1 - Walles, Heike A1 - Egerbacher, Monika A1 - Jenner, Florian T1 - Structure-Function relationships of equine menisci JF - PLoS ONE N2 - Meniscal pathologies are among the most common injuries of the femorotibial joint in both human and equine patients. Pathological forces and ensuing injuries of the cranial horn of the equine medial meniscus are considered analogous to those observed in the human posterior medial horn. Biomechanical properties of human menisci are site-and depth-specific. However, the influence of equine meniscus topography and composition on its biomechanical properties is yet unknown. A better understanding of equine meniscus composition and biomechanics could advance not only veterinary therapies for meniscus degeneration or injuries, but also further substantiate the horse as suitable translational animal model for (human) meniscus tissue engineering. Therefore, the aim of this study was to investigate the composition and structure of the equine knee meniscus in a site-and age-specific manner and their relationship with potential site-specific biomechanical properties. The meniscus architecture was investigated histologically. Biomechanical testing included evaluation of the shore hardness (SH), stiffness and energy loss of the menisci. The SH was found to be subjected to both age and site-specific changes, with an overall higher SH of the tibial meniscus surface and increase in SH with age. Stiffness and energy loss showed neither site nor age related significant differences. The macroscopic and histologic similarities between equine and human menisci described in this study, support continued research in this field. KW - Human Medial Meniscus KW - Articular-Cartilage KW - Biomechanical Properties KW - Compressive Properties KW - Human Knee KW - Collagen KW - Injuries KW - Models KW - Repair KW - Osteoarthritis Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225214 VL - 13 IS - 3 ER - TY - JOUR A1 - Wurmb, T A1 - Schorscher, N A1 - Justice, P A1 - Dietz, S A1 - Schua, R A1 - Jarausch, T A1 - Kinstle, U A1 - Greiner, J A1 - Möldner, G A1 - Müller, J A1 - Kraus, M A1 - Simon, S A1 - Wagenhäuser, U A1 - Hemm, J A1 - Roewer, N A1 - Helm, M T1 - Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators JF - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine N2 - Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important “lessons learned” have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres (“red phone”) is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events. KW - terror attack KW - mass casualties KW - evaluation KW - quality indicators KW - rescue mission Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177054 VL - 26 IS - 87 ER - TY - JOUR A1 - Benoit, Sandrine A1 - Scheurlen, Michael A1 - Goebeler, Matthias A1 - Stoevesandt, Johanna T1 - Structured diagnostic approach and risk assessment in mucous membrane pemphigoid with oesophageal involvement JF - Acta Dermato-Venereologica N2 - Oesophageal involvement in mucous membrane pemphigoid is considered rare, but it may be underdiagnosed. To assess the incidence of oesophageal involvement in a group of patients with newly diagnosed mucous membrane pemphigoid we retrospectively analysed the medical records of 30 consecutive patients with mucous membrane pemphigoid diagnosed between 2006 and 2016 at the Department of Dermatology, University Hospital Würzburg. Twenty-one patients (70%) reported symptoms indicative of oesophageal mucous membrane pemphigoid. Twelve patients (40%) underwent oesophagogastroduodenoscopy, and oesophageal pathology compatible with mucous membrane pemphigoid was endoscopically found in 9 cases (30%). In all patients indirect and direct immunofluorescence were performed. Patients with and without oesophageal involvement did not differ with regard to the results of indirect immunofluorescence on salt-split human skin and monkey oesophagus. Study results demonstrate the necessity of a standardized diagnostic work-up, including adequate tissue samples for direct immunofluorescence, to prevent underdiagnosis of oesophageal mucous membrane pemphigoid. KW - cicatricial pemphigoid KW - mucous membrane pemphigoid KW - oesophagogastroduodenoscopy KW - laminin 332 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176191 VL - 98 ER - TY - JOUR A1 - Kasaragod, Vikram B. A1 - Schindelin, Hermann T1 - Structure–Function Relationships of Glycine and GABAA Receptors and Their Interplay With the Scaffolding Protein Gephyrin JF - Frontiers in Molecular Neuroscience N2 - Glycine and γ-aminobutyric acid (GABA) are the major determinants of inhibition in the central nervous system (CNS). These neurotransmitters target glycine and GABAA receptors, respectively, which both belong to the Cys-loop superfamily of pentameric ligand-gated ion channels (pLGICs). Interactions of the neurotransmitters with the cognate receptors result in receptor opening and a subsequent influx of chloride ions, which, in turn, leads to hyperpolarization of the membrane potential, thus counteracting excitatory stimuli. The majority of glycine receptors and a significant fraction of GABAA receptors (GABAARs) are recruited and anchored to the post-synaptic membrane by the central scaffolding protein gephyrin. This ∼93 kDa moonlighting protein is structurally organized into an N-terminal G-domain (GephG) connected to a C-terminal E-domain (GephE) via a long unstructured linker. Both inhibitory neurotransmitter receptors interact via a short peptide motif located in the large cytoplasmic loop located in between transmembrane helices 3 and 4 (TM3-TM4) of the receptors with a universal receptor-binding epitope residing in GephE. Gephyrin engages in nearly identical interactions with the receptors at the N-terminal end of the peptide motif, and receptor-specific interaction toward the C-terminal region of the peptide. In addition to its receptor-anchoring function, gephyrin also interacts with a rather large collection of macromolecules including different cytoskeletal elements, thus acting as central scaffold at inhibitory post-synaptic specializations. Dysfunctions in receptor-mediated or gephyrin-mediated neurotransmission have been identified in various severe neurodevelopmental disorders. Although biochemical, cellular and electrophysiological studies have helped to understand the physiological and pharmacological roles of the receptors, recent high resolution structures of the receptors have strengthened our understanding of the receptors and their gating mechanisms. Besides that, multiple crystal structures of GephE in complex with receptor-derived peptides have shed light into receptor clustering by gephyrin at inhibitory post-synapses. This review will highlight recent biochemical and structural insights into gephyrin and the GlyRs as well as GABAA receptors, which provide a deeper understanding of the molecular machinery mediating inhibitory neurotransmission. KW - glycine receptors KW - GABAA receptors KW - gephyrin KW - moonlighting protein KW - inhibitory post-synaptic specialization KW - cytoskeletal proteins Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325607 VL - 11 ER - TY - THES A1 - Paul, Ursula Sofia Désirée T1 - Studies on the Reactivity of Iridium Bis(phosphinite) Pincer Complexes towards Phosphines, Boranes and their Lewis Adducts and on the Reactivity of Cyclic (Alkyl)(Amino) Carbenes and Nickel Complexes thereof T1 - Studien hinsichtlich der Reaktivität von Iridium bis(phosphinit)-Pincerkomplexen gegenüber Phosphanen, Boranen und deren Lewis Addukten und bezüglich der Reaktivität von zyklischen (Alkyl)(Amino) Carbenen und Nickelkomplexen davon N2 - The first part of the present work provides an insight into the chemistry of iridium complexes bearing the bis(phosphinite) pincer ligand tBuPOCOP (k3-C6H3-1,3-(OPtBu2)2) towards primary boranes and phosphines as well as phosphine-borane Lewis adducts. It furthermore encloses some more detailed studies on their application as catalyst for the dehydrogenative coupling of the latter compounds. The results presented herein can be divided into three sections: I. synthesis and characterization of aryl dihydroborate ligated iridium(III) complexes II. and aryl phosphine coordinated iridium(I) and dihydrido iridium(III) complexes, III. as well as studies on the reactivity of the parent iridium pincer complexes towards BH3 adducts of primary phosphines, which led to first results in the homogeneous catalytic dehydrocoupling of P-aryl substituted phosphine boranes mediated by such iridium pincer complexes. The second part of the present work provides an insight into the chemistry of cyclic (alkyl)(amino) carbene-stabilized nickel complexes as well as it encloses some more detailed studies on the properties and reactivity of the free carbenes itself. The results presented herein can be divided into four sections: I. synthesis and characterization of cyclic (alkyl)(amino) carbene-stabilized nickel carbonyl complexes, II. which allow the evaluation and quantification of the steric and electronic properties of these cyclic (alkyl)(amino) carbenes, III. first studies on the reactivity of these novel nickel complexes, and IV. investigations on C–F and C–H bond activation at the carbene center of cyclic (alkyl)(amino) carbenes. N2 - Der erste Abschnitt der vorliegenden Arbeit gibt einen vertieften Einblick in die Reaktivität von Iridiumkomplexen, die den bis(Phosphinit)-Pincer tBuPOCOP (k3-C6H3-1,3-(OPtBu2)2) als Liganden aufweisen, gegenüber primären Boranen und Phosphanen sowie gegenüber Phosphan-Boran-Lewis-Paaren. Desweiteren sind detailliertere Untersuchungen zu deren Anwendung als Katalysator zur dehydrogenativen Kupplung von Phosphanboranen enthalten. Die erhaltenen Ergebnisse lassen sich in drei Teilbereiche gliedern: I. Synthese und Charakterisierung von Iridium(III)-Komplexen, die Aryldihydroboratliganden tragen, II. Arylphosphan-koordinierte Iridium(I)- und Iridium(III)-Komplexe, III. sowie Studien zur Reaktivität der zugrundeliegenden Iridiumpincerkomplexe gegenüber BH3-Addukten von primären Phosphanen. Diese führten zu ersten Ergebnissen in der homogen-katalytischen Dehydrokupplung von Phosphanboranen unter Verwendung der Iridiumpincerkomplexe als Katalysator. Der zweite Abschnitt der vorliegenden Arbeit gibt einen Einblick in die Chemie von Nickelkomplexen, die durch zyklische (Alkyl)(Amino) Carbene (cAACs) stabilisiert werden. Desweiteren sind Untersuchungen zu den Eigenschaften und zur Reaktivität der freien Carbene selbst enthalten. Die erhaltenen Ergebnisse lassen sich in vier Teilbereiche gliedern: I. Synthese und Charakterisierung von Nickelkomplexen, die durch zyklische (Alkyl)(Amino) Carbene stabilisiert werden, II. welche die Bestimmung und Quantifizierung von deren sterischen und elektronischen Eigenschaften zulassen, III. erste Studien zur Reaktivität dieser neuartigen Nickelkomplexe, sowie IV. Untersuchungen zur C–F- und C–H-Bindungsaktivierung am Carbenkohlenstoffatom der entsprechenden zyklische (Alkyl)(Amino) Carbene. KW - Iridiumkomplexe KW - Iridium bis(phosphinite) pincer complexes KW - cyclic (alkyl)(amino) carbenes KW - carbene-stabilized nickel complexes KW - Nickelkomplexe KW - Metallorganische Chemie Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151963 ER - TY - THES A1 - van Eeuwijk, Judith Martina Maria T1 - Studies on thrombopoiesis and spleen tyrosine kinase-mediated signaling in platelets T1 - Untersuchungen der Thrombopoese und der spleen tyrosine kinase-vermittelten Signaltransduktion in Thrombozyten N2 - In mammals, anucleate blood platelets are constantly produced by their giant bone marrow (BM) progenitors, the megakaryocytes (MKs), which originate from hematopoietic stem cells. Megakaryopoiesis and thrombopoiesis have been studied intensively, but the exact mechanisms that control platelet generation from MKs remain poorly understood. Using multiphoton intravital microscopy (MP-IVM), thrombopoiesis and proplatelet formation were analyzed in the murine BM in real-time and in vivo, identifying an important role for several proteins, including Profilin1, TRPM7 and RhoA in thrombopoiesis. Currently, it is thought that blood cell precursors, such as MKs, migrate from the endosteal niche towards the vascular niche during maturation. In contrast to this paradigm, it was shown that MKs are homogeneously distributed within the dense BM blood vessel network, leaving no space for vessel-distant niches. By combining results from in vivo MP-IVM, in situ light-sheet fluorescence microscopy (LSFM) of the intact BM as well as computational simulations, surprisingly slow MK migration, limited intervascular space and a vessel-biased MK pool were revealed, contradicting the current concept of directed MK migration during thrombopoiesis. Platelets play an essential role in hemostasis and thrombosis, but also in the pathogenesis of ischemic stroke. Ischemic stroke, which is mainly caused by thromboembolic occlusion of brain arteries, is among the leading causes of death and disability worldwide with limited treatment options. The platelet collagen receptor glycoprotein (GP) VI is a key player in arterial thrombosis and a critical determinant of stroke outcome, making its signaling pathway an attractive target for pharmacological intervention. The spleen tyrosine kinase (Syk) is an essential signaling mediator downstream of GPVI, but also of other platelet and immune cell receptors. In this thesis, it was demonstrated that mice lacking Syk specifically in platelets are protected from arterial thrombus formation and ischemic stroke, but display unaltered hemostasis. Furthermore, it was shown that mice treated with the novel, selective and orally bioavailable Syk inhibitor BI1002494 were protected in a model of arterial thrombosis and had smaller infarct sizes and a significantly better neurological outcome 24 h after transient middle cerebral artery occlusion (tMCAO), also when BI1002494 was administered therapeutically, i.e. after ischemia. These results provide direct evidence that pharmacological Syk inhibition might become a safe therapeutic strategy. The T cell receptor  chain-associated protein kinase of 70 kDA (Zap-70) is also a spleen tyrosine kinase family member, but has a lower intrinsic activity compared to Syk and is expressed in T cells and natural killer (NK) cells, but not in platelets. Unexpectedly, arterial thrombus formation in vivo can occur independently of Syk kinase function as revealed by studies in Sykki mice, which express Zap-70 under the control of intrinsic Syk promoter elements. N2 - In Säugetieren werden kernlose Thrombozyten durch ihren riesigen Knochenmark- (KM-) Vorläuferzellen, die Megakaryozyten (MK), die von hämatopoetischen Stammzellen stammen, ständig produziert. Megakaryopoese und Thrombopoese wurden schon intensiv untersucht, aber die genauen Mechanismen, die die Thrombozytenproduktion aus MK kontrollieren, bleiben weitgehend unverstanden. Mittels Multiphotonen-Intravitalmikroskopie (MP-IVM) wurden Thrombopoese und Proplättchenbildung im murinen KM in Echtzeit in vivo untersucht. Dadurch wurde eine wichtige Rolle für die Proteine Profilin1, TRPM7 und RhoA in der Thrombopoese identifiziert. Derzeit wird angenommen, dass Blutzellvorläufer, wie MK, während der Reifung von der endostalen Nische in Richtung der Gefäßnische migrieren. Im Gegensatz zu diesem Paradigma wurde hier gezeigt, dass MK homogen innerhalb des dichten KM Blutgefäßnetzes verteilt sind, so dass kein Raum für Gefäß-ferne Nischen besteht. Durch Ergebnisse von in vivo MP-IVM, in situ Licht-Blatt-Fluoreszenzmikroskopie (LSFM) des intakten KM sowie Computersimulationen wurden eine überraschend langsame MK-Migration, ein begrenzter intervaskulärer Raum und eine asymmetrische MK-Verteilung gezeigt, was im Widerspruch zum derzeitig akzeptierten Konzept der gerichteten MK-Migration während der Thrombopoese steht. Die Thrombozyten spielen eine wesentliche Rolle nicht nur bei der Hämostase und Thrombose, sondern auch in der Pathogenese des ischämischen Schlaganfalls. Der ischämische Schlaganfall, der vor allem durch einen thromboembolischen Verschluss von Gehirnarterien verursacht wird, ist eine der häufigsten Ursachen für Tod und Behinderung weltweit und die Behandlungsmöglichkeiten sind sehr eingeschränkt. Der thrombozytäre Kollagenrezeptor Glykoprotein (GP) VI ist ein wichtiger Faktor in der arteriellen Thrombose und trägt entscheidend zur Pathogenese des ischämischen Schlaganfalls bei, sodass dessen Signalweg ein attraktives Ziel für pharmakologische Interventionen darstellen könnte. Die spleen tyrosine kinase (Syk) ist ein wichtiges Molekül im GPVI-Signalweg, aber auch in den Signalkaskaden von anderen Thrombozyten- und Immunzellrezeptoren. Es wurde nachgewiesen, dass Mäuse mit einer thrombozytären Syk-Defizienz, vor arterieller Thrombusbildung und ischämischem Schlaganfall geschützt sind, aber unveränderte Hämostase zeigen. Darüber hinaus wurde gezeigt, dass Mäuse, die mit dem neuartigen, selektiven und oral bioverfügbaren Syk-Inhibitor BI1002494 behandelt wurden, geschützt sind in einem Modell der arteriellen Thrombose. Auch hatten sie kleinere Infarkte und eine deutlich bessere neurologische Funktion 24 Stunden nach der transienten Arteria cerebri media Okklusion (tMCAO), auch wenn BI1002494 therapeutisch, d.h. nach der Ischämie, verabreicht wurde. Diese Ergebnisse deuten darauf hin, dass die pharmakologische Hemmung von Syk eine sichere therapeutische Strategie bei Schlaganfall sein könnte. Der T-Zell Rezeptor -chain-associated protein kinase of 70 kDa (Zap-70) ist auch ein spleen tyrosine kinase-Familienmitglied, hat aber eine geringere intrinsische Aktivität im Vergleich zu Syk und wird in T-Zellen und natural killer (NK) Zellen exprimiert, nicht aber in Thrombozyten. Studien in Sykki Mäusen, die unter der Kontrolle der intrinsischen Syk Promotorelemente Zap-70 exprimieren, ergaben, dass die arterielle Thrombusbildung in vivo unabhängig von der Syk-Kinasefunktion stattfinden kann. KW - Thrombose KW - Megakaryozyt KW - Thrombopoese KW - Mikroskopie KW - Hämostase KW - Thrombosis KW - Megakaryocyte KW - Hemostasis KW - Microscopy KW - Thrombopoiesis KW - Platelet KW - Ischemic stroke KW - Spleen tyrosine kinase Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142933 ER - TY - JOUR A1 - Chen, Xinyu A1 - Werner, Rudolf A. A1 - Lapa, Constantin A1 - Nose, Naoko A1 - Hirano, Mitsuru A1 - Javadi, Mehrbod S. A1 - Robinson, Simon A1 - Higuchi, Takahiro T1 - Subcellular storage and release mode of the novel \(^{18}\)F-labeled sympathetic nerve PET tracer LMI1195 JF - EJNMMI Research N2 - Background: \(^{18}\)F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (\(^{18}\)F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. The favorable image quality with high and specific neural uptake has been previously demonstrated in animals and humans, but intracellular behavior is not yet fully understood. The aim of the present study is to verify whether it is taken up in storage vesicles and released in company with vesicle turnover. Results: Both vesicle-rich (PC12) and vesicle-poor (SK-N-SH) norepinephrine-expressing cell lines were used for in vitro tracer uptake studies. After 2 h of \(^{18}\)F-LMI1195 preloading into both cell lines, effects of stimulants for storage vesicle turnover (high concentration KCl (100 mM) or reserpine treatment) were measured at 10, 20, and 30 min. \(^{131}\)I-meta-iodobenzylguanidine (\(^{131}\)I-MIBG) served as a reference. Both high concentration KCl and reserpine enhanced \(^{18}\)F-LMI1195 washout from PC12 cells, while tracer retention remained stable in the SK-N-SH cells. After 30 min of treatment, 18F-LMI1195 releasing index (percentage of tracer released from cells) from vesicle-rich PC12 cells achieved significant differences compared to cells without treatment condition. In contrast, such effect could not be observed using vesicle-poor SK-N-SH cell lines. Similar tracer kinetics after KCl or reserpine treatment were also observed using 131I-MIBG. In case of KCl exposure, Ca\(^{2+}\)-free buffer with the calcium chelator, ethylenediaminetetracetic acid (EDTA), could suppress the tracer washout from PC12 cells. This finding is consistent with the tracer release being mediated by Ca\(^{2+}\) influx resulting from membrane depolarization. Conclusions: Analogous to \(^{131}\)I-MIBG, the current in vitro tracer uptake study confirmed that \(^{131}\)F-LMI1195 is also stored in vesicles in PC12 cells and released along with vesicle turnover. Understanding the basic kinetics of \(^{18}\)FLMI1195 at a subcellular level is important for the design of clinical imaging protocols and imaging interpretation. KW - phaeochromocytoma KW - Positronen-Emissions-Tomografie KW - heart failure KW - sympathetic nervous system KW - storage vesicle turnover KW - positron emission tomography KW - 18F-LMI1195 Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167081 SN - 2191-219X VL - 8 IS - 12 ER - TY - JOUR A1 - Ruf, Katharina A1 - Wirbelauer, Johannes A1 - Beissert, Antje A1 - Frieauff, Eric T1 - Successful treatment of severe arterial hypotension and anuria in a preterm infant with renal tubular dysgenesis– a case report JF - Maternal Health, Neonatology and Perinatology N2 - Background: Oligohydramnios sequence can be caused by renal tubular dysgenesis (RTD), a rare condition resulting in pulmonary and renal morbidity. Besides typical features of Potter-sequence, the infants present with severe arterial hypotension and anuria as main symptoms. Establishing an adequate arterial blood pressure and sufficient renal perfusion is crucial for the survival of these infants. Case presentation: We describe a male preterm infant of 34 + 0 weeks of gestation. Prenatally oligohydramnios of unknown cause was detected. After uneventful delivery and good adaptation the infant developed respiratory distress due to a spontaneous right-sided pneumothorax and required thoracocentesis and placement of a chest tube; he showed no major respiratory concerns thereafter and needed only minimal ventilatory support. Echocardiography revealed no abnormalities, especially no pulmonary hypertension. However, he suffered from severe arterial hypotension and anuria refractory to catecholamine therapy (dobutamine, epinephrine and noradrenaline). After 36 h of life, vasopressin therapy was initiated resulting in an almost immediate stabilization of arterial blood pressure and subsequent onset of diuresis. Therapy with vasopressin was necessary for three weeks to maintain adequate arterial blood pressure levels and diuresis. Sepsis and adrenal insufficiency were ruled out as inflammation markers, microbiological tests and cortisol level were normal. At two weeks of age, our patient developed electrolyte disturbances which were successfully treated with fludrocortisone. He did not need renal replacement therapy. Genetic analyses revealed a novel compound hyterozygous mutation of RTD. Now 17 months of age, the patient is in clinically stable condition with treatment of fludrocortisone and sodium bicarbonate. He suffers from stage 2 chronic kidney disease; blood pressure, motor and cognitive development are normal. Conclusions: RTD is a rare cause of oligohydramnios sequence. Next to pulmonary hypoplasia, severe arterial hypotension is responsible for poor survival. We present the only second surviving infant with RTD, who did not require renal replacement therapy during the neonatal period. It can be speculated whether the use of vasopressin prevents renal replacement therapy as vasopressin increases urinary output by improving renal blood flow. KW - potter sequence KW - oligohydramnios sequence KW - renal tubular dysgenesis KW - arterial hypotension KW - vasopressin KW - respiratory distress KW - anuria KW - preterm KW - dry lung syndrome KW - neonatal renal failure Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177405 VL - 4 IS - 27 ER - TY - THES A1 - Aufmkolk, Sarah T1 - Super-Resolution Microscopy of Synaptic Proteins T1 - Hochauflösende Mikroskopie von Synaptischen Proteinen N2 - The interaction of synaptic proteins orchestrate the function of one of the most complex organs, the brain. The multitude of molecular elements influencing neurological correlations makes imaging processes complicated since conventional fluorescence microscopy methods are unable to resolve structures beyond the diffraction-limit. The implementation of super-resolution fluorescence microscopy into the field of neuroscience allows the visualisation of the fine details of neural connectivity. The key element of my thesis is the super-resolution technique dSTORM (direct Stochastic Optical Reconstruction Microscopy) and its optimisation as a multi-colour approach. Capturing more than one target, I aim to unravel the distribution of synaptic proteins with nanometer precision and set them into a structural and quantitative context with one another. Therefore dSTORM specific protocols are optimized to serve the peculiarities of particular neural samples. In one project the brain derived neurotrophic factor (BDNF) is investigated in primary, hippocampal neurons. With a precision beyond 15 nm, preand post-synaptic sites can be identified by staining the active zone proteins bassoon and homer. As a result, hallmarks of mature synapses can be exhibited. The single molecule sensitivity of dSTORM enables the measurement of endogenous BDNF and locates BDNF granules aligned with glutamatergic pre-synapses. This data proofs that hippocampal neurons are capable of enriching BDNF within the mature glutamatergic pre-synapse, possibly influencing synaptic plasticity. The distribution of the metabotropic glutamate receptor mGlu4 is investigated in physiological brain slices enabling the analysis of the receptor in its natural environment. With dual-colour dSTORM, the spatial arrangement of the mGlu4 receptor in the pre-synaptic sites of parallel fibres in the molecular layer of the mouse cerebellum is visualized, as well as a four to six-fold increase in the density of the receptor in the active zone compared to the nearby environment. Prior functional measurements show that metabotropic glutamate receptors influence voltage-gated calcium channels and proteins that are involved in synaptic vesicle priming. Corresponding dSTORM data indeed suggests that a subset of the mGlu4 receptor is correlated with the voltage-gated calcium channel Cav2.1 on distances around 60 nm. These results are based on the improvement of the direct analysis of localisation data. Tools like coordinated based correlation analysis and nearest neighbour analysis of clusters centroids are used complementary to map protein connections of the synapse. Limits and possible improvements of these tools are discussed to foster the quantitative analysis of single molecule localisation microscopy data. Performing super-resolution microscopy on complex samples like brain slices benefits from a maximised field of view in combination with the visualisation of more than two targets to set the protein of interest in a cellular context. This challenge served as a motivation to establish a workflow for correlated structured illumination microscopy (SIM) and dSTORM. The development of the visualisation software coSIdSTORM promotes the combination of these powerful super-resolution techniques even on separated setups. As an example, synapses in the cerebellum that are affiliated to the parallel fibres and the dendrites of the Purkinje cells are identified by SIM and the protein bassoon of those pre-synapses is visualised threedimensionally with nanoscopic precision by dSTORM. In this work I placed emphasis on the improvement of multi-colour super-resolution imaging and its analysing tools to enable the investigation of synaptic proteins. The unravelling of the structural arrangement of investigated proteins supports the building of a synapse model and therefore helps to understand the relation between structure and function in neural transmission processes. N2 - Das Zusammenspiel von synaptischen Proteinen organisiert präzise die Funktion eines der komplexesten Organe, dem Gehirn. Die Vielfalt der molekularen Bestandteile, die diese neurologischen Beziehungen beeinflussen, verkomplizieren den Bildgebungsprozess, da die konventionellen Fluoreszenzmikroskopiemethoden Strukturen, die kleiner sind als das Beugungslimit, nicht auflösen können. Die Implementierung der hochauflösenden Fluoreszenzmikroskopie in das Gebiet der Neurowissenschaften ermöglicht die Visualisierung feiner Details neurologischer Verbindungen. Die hochauflösende Mikroskopietechnik dSTORM (direct Stochastic Optical Reconstruction Microscopy) und dessen Optimierung als Mehrfarbenanwendung sind Schlüsselelemente meiner Doktorarbeit. Mit der Möglichkeit mehr als ein Protein zu messen, ist es mein Ziel die Verteilung synaptischer Proteine mit nanometer Genauigkeit zu entschlüsseln und diese in ein strukturelles und quantitativ Verhältnis zueinander zu setzen. Aus diesem Grund wurden dSTORM spezifische Protokolle den Besonderheiten der jeweiligen neuronalen Proben angepasst und optimiert. In einem Projekt wird der neurotrophe Faktor BDNF (brain derived neurotrophic factor) in primären hippocampalen Neuronen untersucht. Mit einer Auflösungspräzision von unter 15 nm kann durch eine Färbung der Proteine Bassoon und Homer in der aktiven Zone die prä- und postsynaptische Seite identifiziert werden. Daraus resultierend können Kennzeichen für vollentwickelte Synapsen erfasst werden. Die Einzelmolekülsensitivität von dSTORM ermöglicht erstmalig die Messung von endogenem BDNF und zeigt, dass die BDNF Gruppierungen entlang von glutamatergen Präsynapsen verteilt sind. Diese Daten beweisen, dass hippocampale Neuronen die Möglichkeit haben, BDNF in der vollausgebildeten glutamatergen Präsynapse anzureichern und somit möglicherweise synaptische Plastizität beeinflussen. Die Verteilung des metabotropen Glutamatrezeptors mGlu4 wird in physiologischen Gehirnschnitten untersucht. Das ermöglicht den Rezeptor in seiner natürlichen Umgebung zu analysieren. Mit Zweifarben-dSTORM Messungen wird das räumliche Arrangement der mGlu4 Rezeptoren in der Präsynapse der parallelen Fasern der molekularen Schicht des Mauskleinhirns visualisiert und eine vier- bis sechsfache erhöhte Dichte des Rezeptors in der aktiven Zone, verglichen mit dem näheren Umfeld, aufgezeigt. Vorausgegangende funktionale Messungen zeigen, dass metabotrope Glutamatrezeptoren spannungsgesteuerte Calciumkanäle und Proteine, die in synaptische Vesikelgrundierung involviert sind, beeinflussen. Entsprechende dSTORM Daten deuten darauf hin, dass ein Teil der mGlu4 Rezeptoren mit dem spannungsgesteuerten Calciumkanal Cav2.1 auf einer Distanz von circa 60 nm korreliert ist. Diese Ergebnisse basieren auf der Verbesserung der direkten Analyse der Lokalisationsdatensätze. Werkzeuge, wie die Koordinaten basierte Korrelationsanalyse und die Nächste Nachbaranalyse von Clusterschwerpunkten werden sich ergänzend benutzt, um ein umfassendes Bild von Proteinverbindungen in der Synapse zu erzeugen. Die Grenzen und die Verbesserungsmöglichkeiten dieser Werkzeuge werden diskutiert, um die quantitative Analyse von Einzelmoleküldatensätzen voranzubringen. Die Durchführung von hochauflösender Mikroskopie an komplexen Proben, wie Gehirnschnitten, wird begünstigt durch die Maximierung der Aufnahmefläche in Kombination mit der Möglichkeit mehr als zwei Zielstrukturen zu visualisieren, um somit das Protein von primären Interesse in einen zellulären Zusammenhang zu setzen. Diese Herausforderung hat als Motivation gedient, ein Messprotokoll für korrelierte Strukturierte Beleuchtungsmikroskopie (SIM) und dSTORM zu etablieren. Die Entwicklung der Visualisierungssoftware coSIdSTORM erleichtert die Kombination dieser beiden leistungsstarken, hochauflösenden Techniken, sogar wenn diese auf getrennten Mikroskopieaufbauten umgesetzt werden. Als ein Beispiel werden Synapsen, die zwischen den parallelen Fasern in der molekularen Schicht des Cerebellums und den Purkinje-Zellen ausgebildet werden, mit SIM identifiziert und das Protein Bassoon in diesen Präsynapsen wird mit einer nanometergenauen Präzision drei-dimensional mit dSTORM Messungen visualisiert. In meiner Arbeit habe ich den Fokus auf die Weiterentwickelung von hochauflösender Mehrfarbenmikroskopie und die damit verbundenen analytischen Werkzeuge gelegt, sodass die Untersuchung von synaptischen Proteinen ermöglicht wird. Die Herausarbeitung des strukturellen Arrangements der untersuchten synaptischen Proteine unterstützt den Aufbau eines Models der Synapse und erweitert somit das Verständnis des Zusammenhangs von Struktur und Funktion in neuronalen Übertragungsvorgängen. KW - Hochauflösende Mikroskopie KW - correlative methods KW - Fluoreszenzmikroskopie KW - Synaptische Proteine KW - Korrelative Mikroskopie KW - dSTORM KW - SIM KW - fluorescence KW - super-resolution microscopy KW - localization microscopy KW - two-color microscopy KW - synapse KW - synaptic proteins Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151976 ER - TY - JOUR A1 - Marzocco, Stefania A1 - Fazeli, Gholamreza A1 - Di Micco, Lucia A1 - Autore, Giuseppina A1 - Adesso, Simona A1 - Dal Piaz, Fabrizio A1 - Heidland, August A1 - Di Iorio, Biagio T1 - Supplementation of short-chain fatty acid, sodium propionate, in patients on maintenance hemodialysis: beneficial effects on inflammatory parameters and gut-derived uremic toxins, a pilot study (PLAN Study) JF - Journal of Clinical Medicine N2 - Background: In end-stage renal disease (ESRD), gut-derived uremic toxins play a crucial role in the systemic inflammation and oxidative stress promoting the excess morbidity and mortality. The biochemical derangement is in part a consequence of an insufficient generation of short-chain fatty acids (SCFA) due to the dysbiosis of the gut and an insufficient consumption of the fermentable complex carbohydrates. Aim of the study: The primary end-point was to evaluate the potential efficacy of SCFA (specifically, sodium propionate (SP)) for patients on maintenance hemodialysis (MHD) on systemic inflammation. Secondary end-points included potential attenuation of oxidative stress markers, insulin resistance and production of gut-derived uremic toxins indoxyl sulfate and p-cresol sulfate, as well as health status after SP supplementation. Study design: We performed a single-center non-randomized pilot study in 20 MHD patients. They received the food additive SP with a daily intake of 2 × 500 mg in the form of capsules for 12 weeks. Pre-dialysis blood samples were taken at the beginning, after six weeks and at the end of the administration period, as well as four weeks after withdrawal of the treatment. Results: The subjects revealed a significant decline of inflammatory parameters C-reactive protein (−46%), interleukin IL-2 (−27%) and IL-17 (−15%). The inflammatory parameters IL-6 and IFN-gamma showed a mild non-significant reduction and the anti-inflammatory cytokine IL-10 increased significantly (+71%). While the concentration of bacterial endotoxins and TNF-α remained unchanged, the gut-derived uremic toxins, indoxyl sulfate (−30%) and p-cresyl sulfate (−50%), revealed a significant decline. The SP supplementation reduced the parameters of oxidative stress malondialdehyde (−32%) and glutathione peroxidase activity (−28%). The serum insulin levels dropped by 30% and the HOMA-index by 32%. The reduction of inflammatory parameters was associated with a lowering of ferritin and a significant increase in transferrin saturation (TSAT). Four weeks after the end of the treatment phase, all improved parameters deteriorated again. Evaluation of the psycho-physical performance with the short form 36 (SF-36) questionnaire showed an enhancement in the self-reported physical functioning, general health, vitality and mental health. The SP supplementation was well tolerated and without important side effects. No patient had left the study due to intolerance to the medication. The SP supplementation in MHD patients reduced pro-inflammatory parameters and oxidative stress and improved insulin resistance and iron metabolism. Furthermore, SP effectively lowered the important gut-derived uremic toxins indoxyl and p-cresol sulfate. These improvements were associated with a better quality of life. Further controlled studies are required in a larger cohort to evaluate the clinical outcome. KW - propionic acid KW - chronic kidney disease KW - hemodialysis KW - gut microbiome KW - systemic micro-inflammation oxidative stress KW - indoxyl sulfate KW - p-cresyl sulfate Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197626 SN - 2077-0383 VL - 7 IS - 10 ER - TY - THES A1 - Kunz, Valentin T1 - Supramolecular Approaches for Water Oxidation Catalysis with Ruthenium Complexes T1 - Supramolekulare Ansätze für die Wasseroxidationskatalyse mit Rutheniumkomplexen N2 - The catalytic splitting of water into its elements is an important reaction to establish hydrogen as a solar fuel. The bottle-neck of this process is considered to be the oxidative half reaction generating oxygen, and good catalysts are required to handle the complicated redox chemistry involved. As can be learned from nature, the incorporation of the catalytically active species into an appropriate matrix can help to improve the overall performance. Thus, the aim of the present thesis was to establish novel supramolecular approaches to improve water oxidation catalysis using the catalytically active {Ru(bda)} fragment as key motive (bda = 2,2'-bipyridine-6,6'-dicarboxylate). First, the synthesis of ruthenium catalysts gathering three {Ru(bda)} water oxidation subunits in a macrocyclic fashion is described. By using bridging bipyridine ligands of different lengths, metallosupramolecular macrocycles with distinct sizes have been obtained. Interestingly, an intermediate ring size has been proven to be optimal for the catalytic water oxidation. Detailed kinetic, spectroscopic, and theoretical studies helped to identify the reaction mechanism and to rationalize the different catalytic activities. Furthermore, solubilizing side chains have been introduced for the most active derivative to achieve full water solubility. Secondly, the {Ru(bda)} fragment was embedded into supramolecular aggregates to generate more stable catalytic systems compared to a homogeneous reference complex. Therefore, the catalyst fragment was equipped with axial perylene bisimide (PBI) ligands, which facilitate self-assembly. Moreover, the influence of the different accessible aggregate morphologies on the catalytic performance has been investigated. N2 - Die katalytische Spaltung von Wasser in seine Elemente ist eine wichtige Reaktion für die Erzeugung von Wasserstoff als alternativem Brennstoff. Die Sauerstoff-erzeugende Halbreaktion gilt gemeinhin als Flaschenhals dieses Prozesses, weshalb effiziente Katalysatoren benötigt werden um die komplizierte Redoxchemie zu bewältigen. Die Natur als Vorbild lehrt uns, dass die Einbettung katalytisch aktiver Zentren in eine unterstützende Matrix dazu beitragen kann deren Leistung erheblich zu steigern. Ziel der vorliegenden Dissertation war daher die Etablierung neuartiger supramolekularer Ansätze zur Verbesserung der Wasseroxidationskatalyse. Als Katalysator-Leitmotiv diente das {Ru(bda)}-Fragment (bda = 2,2'-Bipyridin-6,6'-dicarboxylat). Zunächst wird die Synthese von Rutheniumkatalysatoren beschrieben, in denen drei {Ru(bda)}-Zentren in makrozyklischer Weise verknüpft sind. Durch die Verwendung von verbrückenden Bipyridin-Liganden unterschiedlicher Länge wurden metallosupramolekulare Makrozyklen mit verschiedenen Ringgrößen erhalten. Interessanterweise erwies sich eine mittlere Größe als optimal für die katalytische Wasseroxidation. Detaillierte kinetische, spektroskopische und theoretische Untersuchungen haben dazu beigetragen, den Reaktionsmechanismus zu identifizieren und die verschiedenen katalytischen Aktivitäten zu erklären. Darüber hinaus wurden löslichkeitsfördernde Seitenketten für den aktivsten Makrozyklus eingeführt, um eine vollständige Wasserlöslichkeit zu erreichen. Darüber hinaus wurde das {Ru(bda)}-Fragment in supramolekulare Aggregate eingebettet, um im Vergleich zu einem homogenen Referenzkomplex stabilere katalytische Systeme zu erzeugen. Dafür wurde das Katalysatorfragment mit axialen Perylenbisimid-Liganden ausgestattet, welche zur Selbstassemblierung neigen. In diesem Zusammenhang wurde der Einfluss der verschiedenen zugänglichen Aggregatmorphologien auf die katalytische Aktivität untersucht. KW - Ruthenium Komplexe KW - Metallosupramolekulare Chemie KW - Katalyse KW - Wasseroxidation KW - ruthenium complexes KW - metallosupramolecular chemistry KW - catalysis KW - water oxidation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154820 ER - TY - THES A1 - Lutz, Peter T1 - Surface and Interface Electronic Structure in Ferroelectric BaTiO\(_3\) T1 - Die elektronische Struktur an der Grenz- und Oberfläche des Ferroelektrikums BaTiO\(_3\) N2 - Transition metal oxides (TMO) represent a highly interesting material class as they exhibit a variety of different emergent phenomena including multiferroicity and superconductivity. These effects result from a significant interplay of charge, spin and orbital degrees of freedom within the correlated d-electrons. Oxygen vacancies (OV) at the surface of certain d0 TMO release free charge carriers and prompt the formation of a two-dimensional electron gas (2DEG). Barium titanate (BaTiO3) is a prototypical and promising d0 TMO. It displays ferroelectricity at room temperature and features several structural phase transitions, from cubic over tetragonal (at room temperature) and orthorhombic to rhombohedral. The spontaneous electric polarization in BaTiO3 can be used to manipulate the physical properties of adjacent materials, e.g. in thin films. Although the macroscopic properties of BaTiO3 are studied in great detail, the microscopic electronic structure at the surface and interface of BaTiO3 is not sufficiently understood yet due to the complex interplay of correlation within the d states, oxygen vacancies at the surface, ferroelectricity in the bulk and the structural phase transitions in BaTiO3. This thesis investigates the electronic structure of different BaTiO3 systems by means of angle-resolved photoelectron spectroscopy (ARPES). The valence band of BaTiO3 single crystals is systematically characterized and compared to theoretical band structure calculations. A finite p-d hybridization of titanium and oxygen states was inferred at the high binding energy side of the valence band. In BaTiO3 thin films, the occurrence of spectral weight near the Fermi level could be linked to a certain amount of OV at the surface which effectively dopes the host system. By a systematic study of the metallic surface states as a function of temperature and partial oxygen pressure, a model was established which reflects the depletion and accumulation of charge carriers at the surface of BaTiO3. An instability at T ~ 285K assumes a volatile behavior of these surface states. The ferroelectricity in BaTiO3 allows a control of the electronic structure at the interface of BaTiO3-based heterostructures. Therefore, the interface electronic structure of Bi/BaTiO3 was studied with respect to the strongly spin-orit coupled states in Bi by also including a thickness dependent characterization. The ARPES results, indeed, confirm the presence of Rashba spin-split electronic states in the bulk band gap of the ferroelectric substrate. By varying the film thickness in Bi/BaTiO3, it was able to modify the energy position and the Fermi vector of the spin-split states. This observation is associated with the appearance of an interface state which was observed for very low film thickness. Both spectral findings suggest a significant coupling between the Bi films and BaTiO3. N2 - Übergangsmetalloxide stellen eine hochinteressante Materialklasse dar, da sie eine Vielzahl neuartiger Phänomene, wie z.B. multiferroische Eigenschaften und Supraleitung, aufweisen. Diese Effekte sind die Folge eines komplexen Zusammen- spiels zwischen den Freiheitsgraden von Ladung, Spin und der orbitalen Komponente innerhalb eines korrelierten d-Elektronensystems. Sauerstoffstörstellen an der Ober- fläche von einigen dieser Systeme führen zu der Ausbildung freier Ladungsträger und der damit verbundenen Erzeugung eines 2-dimensionalen Elektronengases (2DEG). Das in dieser Arbeit untersuchte Bariumtitanat (BaTiO3) ist ein typisches und sehr vielversprechendes d0-Übergangsmetalloxid. Zum einen ist es ferroelektrisch bei Raumtemperatur und zum anderen weist es mehrere strukturelle Phasenübergänge auf, von kubisch über tetragonal (bei Raumtemperatur) und orthorhombisch zu rhom- boedrisch. Die spontane elektrische Polarisation in BaTiO3 kann dazu verwendet werden um physikalische Eigenschaften angrenzender Materialsysteme, z.B. von Dünnfilmen, zu beeinflussen. Obwohl vor allem die makroskopischen ferroelektrischen Eigenschaften von BaTiO3 bereits detailliert untersucht wurden, ist die mikrosko- pische elektronische Struktur in BaTiO3 und in BaTiO3-Grenzflächen noch nicht voll- ständig verstanden. Der Grund hierfür ist ein komplexes Wechselspiel zwischen elek- tronischen Korrelationseffekten, Sauerstoffstörstellen, Ferroelektrizität und struk- turellen Aspekten. Diese Dissertation befasst sich mit der elektronischen Struktur von verschiede- nen BaTiO3-Systemen, unter Verwendung der winkelaufgelösten Photoelektronen- spektroskopie (PES). Zum einen wurde das Valenzband von BaTiO3-Einkristallen systematisch untersucht und mit theoretischen Rechnungen verglichen. Dabei konnte eine endliche p-d-Hybridisierung von Titan- mit Sauerstoff-Zuständen im Valenzband festgestellt werden. Weiterhin wurde in BaTiO3-Dünnfilmen das Auftreten von spek- tralem Gewicht nahe des Ferminiveaus beobachtet. Diese metallischen Zustände sind auf eine erhöhte Dichte von Sauerstoffstörstellen an der Oberfläche zurückzuführen, wodurch das System effektiv dotiert wird. Die systematische Untersuchung der elek- tronischen Struktur in Abhängigkeit von Temperatur und Sauerstoff-Partialdruck wurde erfolgreich durch ein Modell beschrieben, das eine Instabilität der metallischen Zustände bei T ≈ 285K aufzeigt. Die ferroelektrische Eigenschaft von BaTiO3 kann in Heterostrukturen dazu verwendet werden, um die elektronische Struktur an der Grenzfläche zu kontrol- lieren. Zu diesem Zweck wurde in dieser Arbeit die mikroskopische elektronische Struktur an der Grenzfläche von Bi/BaTiO3 bedeckungsabhängig charakterisiert und im Hinblick auf die spin-polarisierten Zustände in Bi untersucht. So konnten Rashba-spinaufgespaltene elektronische Zustände in der Volumenbandlücke des fer- roelektrischen Substrates nachgewiesen werden. Eine Variation der Filmdicke in Bi/BaTiO3 führte zu einer energetischen Verschiebung und zu einer Änderung des Fermivektors der spinaufgespaltenen Zustände. Diese Beobachtung hängt stark mit dem Ausbilden eines Grenzflächenzustandes zusammen, der für sehr niedrige Be- deckungen beobachtet wurde. Beide Effekte weisen zudem auf eine Wechselwirkung zwischen den Bi-Filmen und BaTiO3 KW - Bariumtitanat KW - Photoelektronenspektroskopie KW - Ferroelektrikum KW - Spintronik KW - Niederdimensionales Elektronengas KW - barium titanate KW - photoelectron spectroscopy KW - ferroelectricity KW - spintronic KW - two-dimensional electron gas Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159057 ER - TY - JOUR A1 - Gore, Lia A1 - Locatelli, Franco A1 - Zugmaier, Gerhard A1 - Handgretinger, Rupert A1 - O'Brien, Maureen M. A1 - Bader, Peter A1 - Bhojwani, Deepa A1 - Schlegel, Paul-Gerhardt A1 - Tuglus, Catherine A. A1 - Stackelberg, Arend von T1 - Survival after blinatumomab treatment in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia JF - Blood Cancer Journal N2 - no abstract available KW - acute lymphocytic leukaemia KW - immunotherapy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230726 VL - 8 ER - TY - JOUR A1 - Ranger, Christopher M. A1 - Biedermann, Peter HW A1 - Phuntumart, Vipaporn A1 - Beligala, Gayathri U. A1 - Ghosh, Satyaki A1 - Palmquist, Debra E. A1 - Mueller, Robert A1 - Barnett, Jenny A1 - Schultz, Peter B. A1 - Reding, Michael E. A1 - Benz, J. Philipp T1 - Symbiont selection via alcohol benefits fungus farming by ambrosia beetles JF - Proceedings of the National Academy of Sciences N2 - Animal-microbe mutualisms are typically maintained by vertical symbiont transmission or partner choice. A third mechanism, screening of high-quality symbionts, has been predicted in theory, but empirical examples are rare. Here we demonstrate that ambrosia beetles rely on ethanol within host trees for promoting gardens of their fungal symbiont and producing offspring. Ethanol has long been known as the main attractant for many of these fungus-farming beetles as they select host trees in which they excavate tunnels and cultivate fungal gardens. More than 300 attacks by Xylosandrus germanus and other species were triggered by baiting trees with ethanol lures, but none of the foundresses established fungal gardens or produced broods unless tree tissues contained in vivo ethanol resulting from irrigation with ethanol solutions. More X. germanus brood were also produced in a rearing substrate containing ethanol. These benefits are a result of increased food supply via the positive effects of ethanol on food-fungus biomass. Selected Ambrosiella and Raffaelea fungal isolates from ethanol-responsive ambrosia beetles profited directly and indirectly by (i) a higher biomass on medium containing ethanol, (ii) strong alcohol dehydrogenase enzymatic activity, and (iii) a competitive advantage over weedy fungal garden competitors (Aspergillus, Penicillium) that are inhibited by ethanol. As ambrosia fungi both detoxify and produce ethanol, they may maintain the selectivity of their alcohol-rich habitat for their own purpose and that of other ethanol-resistant/producing microbes. This resembles biological screening of beneficial symbionts and a potentially widespread, unstudied benefit of alcohol-producing symbionts (e.g., yeasts) in other microbial symbioses. KW - fungus-farming insects KW - plant-insect-microbe interactions KW - symbiosis KW - insect-fungus mutualism KW - host screening Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224953 VL - 115 IS - 17 ER - TY - JOUR A1 - Boelch, Sebastian P. A1 - Roth, Magnus A1 - Arnholdt, Joerg A1 - Rudert, Maximilian A1 - Luedemann, Martin T1 - Synovial fluid aspiration should not be routinely performed during the two-stage exchange of the knee JF - BioMed Research International N2 - Purpose. Detection of infection persistence during the two-stage exchange of the knee for periprosthetic joint infection is challenging. Synovial fluid culture (SFC) and synovial white blood cell count (SWBCC) before joint reimplantation are widespread diagnostic means for this indication. The sensitivity and specificity of SFC and of SWBCC for infection persistence before planned reimplantation were evaluated. Methods. 94 two-stage exchanges of the knee with synovial fluid aspiration performed after a drug holiday of at least 14 days and before reimplantation or spacer exchange (planned reimplantation) were retrospectively analyzed. Only cases with at least 3 intraoperative samples at planned reimplantation were included. SFC and SWBCC were compared to pathogen detection (SFC\(_{(culture)}\)/SWBCC\(_{(culture)}\) and to histopathological signs of infection persistence (SFC\(_{(histo)}\)/SWBCC\(_{(histo)}\) from intraoperative samples at planned reimplantation. For SFC, the sensitivity and specificity were calculated. For SWBCC, the optimal cut-off value with its sensitivity and specificity was calculated with the Youden-Index. Results. Sensitivity and specificity of SFC\(_{(culture)}\) were 0.0% and 98.9%. Sensitivity and specificity of SFC\(_{(histo)}\) were 3.4% and 100%. The optimal cut-off value for SWBCC\(_{(culture)}\) was 4450 cells/μl with a sensitivity of 50.0% and a specificity of 86.5%. The optimal cut-off value for SWBCC\(_{(histo)}\) was 3250 cells/μl with a sensitivity of 35.7% and a specificity of 92.9%. Conclusion. The detection of infection persistence remains challenging and a consented approach is lacking. The results do not warrant the routine performance of SFC during the two-stage exchange at the knee. SWBCC can be used to confirm infection persistence at high cut-offs, but they only occur in few patients and are therefore inappropriate for the routine use. KW - knee KW - two-stage exchange KW - Synovial Fluid Aspiration Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176800 VL - 2018 IS - 6720712 ER - TY - THES A1 - Schäfer, Julian T1 - Synthesis and Photophysical Investigation of Donor-Acceptor-Substituted meta- and para-Benzene Derivatives T1 - Synthese und Photophysikalische Untersuchung Donor-Akzeptor-Substituierter meta- und para-Benzolderivate N2 - Im ersten Teil dieser Arbeit wurde die erfolgreiche Synthese einer Serie von bisTriarylamin (bisTAA) Verbindungen vorgestellt. Zum einen wurde das Substitutionmuster an der Benzol Brückeneinheit in Form einer meta- bzw. para-Ständigkeit der Redoxzentren (pX bzw. mX), und zum anderen die energetische Lage der Brückeneinheit durch zwei elektronen-schiebende oder ziehende Substituenten X (mit X = OMe, Me, Cl, CN, NO2) in 2,5-Position variiert. Im Falle der meta-Serie wurden auch einige in 4,6-Position substituierte Verbinungen hergestellt (mX46). Die neutral Verbindungen wurden bezüglich ihrer elektrochemischen und photophysikalischen Eigenschaften untersucht. Durch Oxidation konnten die gemischt valenten (MV), kationischen bisTAA-Verbindungen erzeugt werden. Der thermisch induzierte Lochtransfer (HT) wurde durch temperatur-abhängige ESR-Spektroskopie untersucht. Während die HT-Rate k und HT-Barriere ΔG in mX unbeeinflusst von den Substituenten X sind, steigen gleichzeitig k und ΔG in der pX-Serie mit zunehmenden Elektonenschub von X an. Diese zunächst widersprüchliche Beobachtung konnte durch einen ansteigenden Einfluss von Lösungsmitteleffekten und dadurch resultierend, einer zusätzlichen effektiven Barriere erklärt werden. Der optisch induzierte Lochtransfer wurde mittels UV/Vis/NIR-Spektroskopie untersucht. Die pX-Serie zeigte eine Zuhname der elektronischen Kopplung V und dementsprechende eine Abnahme von ΔG, mit Anstieg des elektonenschiebenden Charakters von X. Für mX war eine spektroskopische Bestimmung dieser Parameter nicht möglich. Die mX46-Serie zeigte ein intermediäres Verhalten, wobei MV-Verbindungen mit stark elektronenschiebenden X eine ähnliche hohe Kopplungen wie pX aufwiesen, was mit Hilfe von DFT-Rechnungen bezüglich der Molekülorbitale erklärt werden konnte. Im zweiten Teil dieser Arbeit wurde die Synthese einer Serie von Verbindungen mit Triarylamin (TAA) als Donor und Naphthalindiimid (NDI) als Akzeptor vorgestellt. Auch hier wurde zum einen das Substitutionmuster an der Benzol-Brückeneinheit in Form einer meta- bzw. para-Ständigkeit der Redoxzentren (pXNDI bzw. mXNDI) variieiet und die energetische Lage der durch X (mit X = OMe, Me, Cl, CN, NO2) in 2,5-Position variiert. Außerdem wurde die in 4,6-Position substituierte Verbinungen mOMe46NDI hergestellt. Alle Verbindungen wurden bezüglich ihrer elektochemischen und photophysikalischen Eigenschaften untersucht. Die Elektronentransferprozesse der Ladungsseparierung (CS) und Ladungsrekombination (CR) dieser Verbindungen sollten mittels transienter Absorptionsspektroskopie (TA) in Toluol untersucht werden. Für die Nitroverbindungen p-/mNO2NDI war dies nicht möglich, da sich diese unter Bestrahung zersetzten. Die CR von pXNDI waren nicht im ns-Bereich detektierbar, weshalb sich auf die mXNDI-Serie (mit X = OMe–CN) konzentriert wurde. Die CS wurde mittels fs-TA untersucht. Nach optischer Anregung konnte die Bildung eines CS-Zustandes detektiert werden, dessen Bildungsgeschwindigkeit hin zu elektronen-ziehenden Substituenten X steigt. Die CR wurde mit ns-TA untersucht. Sie findet in der Marcus invertierten Region statt und zeichnet sich wird durch ein biexponentialles Abklingverhaten, was durch ein Singulet-Triplett Gleichgewicht im CS-Zustand zustande kommt, aus. Durch Anlegen eines externen Magnetfeldes ließ sich das Abklingverhalten entscheidend verändern und es konnte eine Singulett-Triplett Aufspaltung nachgewiesen werden. Dieser Befund konnte weiterhin durch Simulation der Abklingkurven bestätigt werden. In beiden Teilen dieser Arbeit konnte ein entscheidender Einfluss der Benzolbrücke auf die auftretenden Ladungstransferprozesse gezeigt werden. Für den HT in Grundzustand der MV bisTAA Verbindungen, sowie der ET im angeregten Zustand der Donor-Akzeptor-Verbindungen, wurden die höchsten ET-Raten für die para-Serien pX und pXNDI gefunden, während die meta-Serien mX und mXNDI deutlch kleine Transferraten aufwiesen. In beiden Studien zeigten die meta46-Verbindungen mX46 und mOMeNDI46 ein intermediäres Verhalten, zwischen denen der para- und meta-Verbindungen. N2 - In the first part of this thesis, the synthesis of a series of bistriarylamine (bisTAA) compounds was presented. On the one hand, the substitution pattern of the TAA at the benzene bridging unit was varied from meta- to para-position (pX and mX), on the other hand, the energetic position of the bridging unit was tuned by use of two electron-donating or electron-accepting substituents X (with X = OMe, Me, Cl, CN, NO2) in 2,5-position. In case of the meta-series, compounds with X in 4,6-position were synthesized (mX46). The photophysical and electrochemical properties of the neutral compounds were investigated. The cationic mixed valence (MV) bisTAA compounds could be generated by oxidation. Thermally induced hole transfer (HT) in the groud state was investigated by temperature depending ESR spectroscopy. While the HT rate k and HT barrier ΔG in mX are unaffected by the substituents X, k and ΔG in the pX series increase simultaneously with increasing electron-donating strength of X. This, at first contradictory observation can be explained by an increasingly important solvent dynamic effect and an additional, effective barrier. The optically induced HT was examined by UV/Vis/NIR spectroscopy. The pX-series revealed an increase of the electronic coupling V, and correspondingly a decrease of ΔG, with an increase of the electron donating character of X. For mX, a spectroscopic determination of these parameters was not possible. mX46 showed an intermediate behavior, MV compounds with strong electron-donating X, obtained coupling of similar magnitude as pX, which could be explained by means of DFT calculations, with regard to the molecular orbitals. In the second part of this work, the synthesis of a series of dyads with triarylamine (TAA) as a donor and naphthalene diimide (NDI) as an acceptor was presented. Again, the substitution pattern of the redox centers at the benzene bridging unit was varied in the form of a meta- or para-position (pXNDI or mXNDI) and the energetic position of the bridging unit was varied by X (with X = OMe, Me, Cl, CN, NO2) attached in the 2,5-position. Additionally, compound mOMe46NDI with methoxy substitution in 4,6-position was synthesized. The photophysical and electrochemical properties of these compounds were investigated. The electron transfer (ET) processes of charge separation (CS) and charge recombination (CR) of these were investigated by means of transient absorption (TA) spectroscopy in toluene. This was not possible for the nitro-compounds p-/mNO2NDI, since they decomposed under irradiation. In addition to that, the CR of pXNDI was not detectable by ns-setup, which is why the focus was given to the mXNDI series (with X = OMe–CN).The CS was examined by fs-TA spectroscopy, where the formation of a CS state could be detected. The rise time of the CS states decreases with increasing electron-withdrawing substituents X. CR was examined with ns-TA spectroscopy and shows a biexponential decay behavior, which is caused by singlet-triplet equilibrium in the CS state. By applying an external magnetic field, the decay behavior was decisively changed and the singlet-triplet splitting could be determined. This finding could also be confirmed by simulating the decay curves. In both parts of this work, the decisive influence of the benzene bridging unit on the appearing ET processes became obvious. For the HT in the ground state of the MV compound, as well as for the ET in the exited states of the DA compounds, the highest transfer rates were found for the para-series pX and pXNDI, and much smaller rates for the meta-series mX and mXNDI. The meta46-compounds mX46 and mOMeNDI46 showed an intermediate behavior in both parts of this work. KW - Synthese KW - Elektronentransfer KW - UV-VIS-Spektroskopie KW - Magnetfeldeffekt KW - intervalence charge transfer KW - transient absorption spectroscopy Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155007 ER -