@phdthesis{Pahlavan2019,
  author    = {Pahlavan, Pirasteh},
  title     = {Integrated Systems Biology Analysis; Exemplified on Potyvirus and Geminivirus interaction with \(Nicotiana\) \(benthamiana\)},
  doi       = {10.25972/OPUS-15341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-153412},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Viral infections induce a significant impact on various functional categories of biological processes in the host. The understanding of this complex modification of the infected host immune system requires a global and detailed overview on the infection process. Therefore it is essential to apply a powerful approach which identifies the involved components conferring the capacity to recognize and respond to specific pathogens, which in general are defeated in so-called compatible virus-plant infections. Comparative and integrated systems biology of plant-virus interaction progression may open a novel framework for a systemic picture on the modulation of plant immunity during different infections and understanding pathogenesis mechanisms. In this thesis these approaches were applied to study plant-virus infections during two main viral pathogens of cassava: Cassava brown streak virus and African cassava mosaic virus. Here, the infection process was reconstructed by a combination of omics data-based analyses and metabolic network modelling, to understand the major metabolic pathways and elements underlying viral infection responses in different time series, as well as the flux activity distribution to gain more insights into the metabolic flow and mechanism of regulation; this resulted in simultaneous investigations on a broad spectrum of changes in several levels including the gene expression, primary metabolites, and enzymatic flux associated with the characteristic disease development process induced in Nicotiana benthamiana plants due to infection with CBSV or ACMV. Firstly, the transcriptome dynamics of the infected plant was analysed by using mRNA-sequencing, in order to investigate the differential expression profile according the symptom developmental stage. The spreading pattern and different levels of biological functions of these genes were analysed associated with the infection stage and virus entity. A next step was the Real-Time expression modification of selected key pathway genes followed by their linear regression model. Subsequently, the functional loss of regulatory genes which trigger R-mediated resistance was observed. Substantial differences were observed between infected mutants/transgenic lines and wild-types and characterized in detail. In addition, we detected a massive localized accumulation of ROS and quantified the scavenging genes expression in the infected wild-type plants relative to mock infected controls. Moreover, we found coordinated regulated metabolites in response to viral infection measured by using LC-MS/MS and HPLC-UV-MS. This includes the profile of the phytohormones, carbohydrates, amino acids, and phenolics at different time points of infection with the RNA and DNA viruses. This was influenced by differentially regulated enzymatic activities along the salicylate, jasmonate, and chorismate biosynthesis, glycolysis, tricarboxylic acid cycle, and pentose phosphate pathways, as well as photosynthesis, photorespiration, transporting, amino acid and fatty acid biosynthesis. We calculated the flux redistribution considering a gradient of modulation for enzymes along different infection stages, ranging from pre-symptoms towards infection stability. Collectively, our reverse-engineering study consisting of the generation of experimental data and modelling supports the general insight with comparative and integrated systems biology into a model plant-virus interaction system. We refine the cross talk between transcriptome modification, metabolites modulation and enzymatic flux redistribution during compatible infection progression. The results highlight the global alteration in a susceptible host, correlation between symptoms severity and the alteration level. In addition we identify the detailed corresponding general and specific responses to RNA and DNA viruses at different stages of infection. To sum up, all the findings in this study strengthen the necessity of considering the timing of treatment, which greatly affects plant defence against viral infection, and might result in more efficient or combined targeting of a wider range of plant pathogens.},
  language  = {en}
}
@phdthesis{Romanov2019,
  author    = {Romanov, Natalie},
  title     = {Characterizing Variation of Protein Complexes and Functional Modules on a Temporal Scale and across Individuals},
  doi       = {10.25972/OPUS-16813},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168139},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {A fundamental question in current biology concerns the translational mechanisms leading from genetic variability to phenotypes. Technologies have evolved to the extent that they can efficiently and economically determine an individual's genomic composition, while at the same time big data on clinical profiles and diagnostics have substantially accumulated. Genome-wide association studies linking genomic loci to certain traits, however, remain limited in their capacity to explain the cellular mechanisms that underlie the given association. For most associations, gene expression has been blamed; yet given that transcript and protein abundance oftentimes do not correlate, that finding does not necessarily decrypt the underlying mechanism. Thus, the integration of further information is crucial to establish a model that could prove more accurate in predicting genotypic effects on the human organism. In this work we describe the so-called proteotype as a feature of the cell that could provide a substantial link between genotype and phenotype. Rather than looking at the proteome as a set of independent molecules, we demonstrate a consistent modular architecture of the proteome that is driven by molecular cooperativity. Functional modules, especially protein complexes, can be further interrogated for differences between individuals and tackled as imprints of genetic and environmental variability. We also show that subtle stoichiometric changes of protein modules could have broader effects on the cellular system, such as the transport of specific molecular cargos. The presented work also delineates to what extent temporal events and processes influence the stoichiometry of protein complexes and functional modules. The re-wiring of the glycolytic pathway for example is illustrated as a potential cause for an increased Warburg effect during the ageing of the human bone marrow. On top of analyzing protein abundances we also interrogate proteome dynamics in terms of stability and solubility transitions during the short temporal progression of the cell cycle. One of our main observations in the thesis encompass the delineation of protein complexes into respective sub-complexes according to distinct stability patterns during the cell cycle. This has never been demonstrated before, and is functionally relevant for our understanding of the dis- and assembly of large protein modules. The insights presented in this work imply that the proteome is more than the sum of its parts, and primarily driven by variability in entire protein ensembles and their cooperative nature. Analyzing protein complexes and functional modules as molecular reflections of genetic and environmental variations could indeed prove to be a stepping stone in closing the gap between genotype and phenotype and customizing clinical treatments in the future.},
  subject      = {Proteotype},
  language  = {en}
}
@phdthesis{Goetz2019,
  author    = {G{\"o}tz, Felix Johannes},
  title     = {Social Cueing of Numerical Magnitude : Observed Head Orientation Influences Number Processing},
  doi       = {10.25972/OPUS-18716},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187161},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {In many parts of the modern world, numbers are used as tools to describe spatial relationships, be it heights, latitudes, or distances. However, this connection goes deeper as a myriad of studies showed that number representations are rooted in space (vertical, horizontal, and/or radial). For instance, numbers were shown to affect spatial perception and, conversely, perceptions or movements in space were shown to affect number estimations. This bidirectional link has already found didactic application in the classroom when children are taught the meaning of numbers. However, our knowledge about the cognitive (and neuropsychological) processes underlying the numerical magnitude operations is still very limited. Several authors indicated that the processing within peripersonal space (i.e. the space surrounding the body in reaching distance) and numerical magnitude operations are functionally equivalent. This assumption has several implications that the present work aims at describing. For instance, vision and visuospatial attention orienting play a prominent role for processing within peripersonal space. Indeed, both neuropsychological and behavioral studies also suggested a similar role of vision and visuospatial attention orienting for number processing. Moreover, social cognition research showed that movements, posture and gestures affect not only the representation of one's own peripersonal space, but also the visuospatial attention behavior of an observer. Against this background, the current work tests the specific implication of the functional equivalence assumption that the spatial attention response to an observed person's posture should extend to the observer's numerical magnitude operations. The empirical part of the present work tests the spatial attention response of observers to vertical head postures (with continuing eye contact to the observer) in both perceptual and numerical space. Two experimental series are presented that follow both steps from the observation of another person's vertical head orientation (within his/her peripersonal space) to the observer's attention orienting response (Experimental series A) as well as from there to the observer's magnitude operations with numbers (Experimental Series B). Results show that the observation of a movement from a neutral to a vertical head orientation (Experiment 1) as well as the observation of the vertical head orientation alone (Experiment 3) shifted the observer's spatial attention in correspondence with the direction information of the observed head (up vs. down). Movement from a vertical to a neutral end position, however, had no effect on the observer's spatial attention orienting response (Experiment 2). Furthermore, following down-tilted head posture (relative to up- or non-tilted head orientation), observers generated smaller numbers in a random number generation task (range 1- 9, Experiment 4), gave smaller estimates to numerical trivia questions (mostly multi-digit numbers, Experiment 5) and chose response keys less frequently in a free choice task that was associated with larger numerical magnitude in a intermixed numerical magnitude task. Experimental Series A served as groundwork for Experimental Series B, as it demonstrated that observing another person's head orientation indeed triggered the expected directional attention orienting response in the observer. Based on this preliminary work, the results of Experimental Series B lend support to the assumption that numerical magnitude operations are grounded in visuospatial processing of peripersonal space. Thus, the present studies brought together numerical and social cognition as well as peripersonal space research. Moreover, the Empirical Part of the present work provides the basis for elaborating on the role of processing within peripersonal space in terms of Walsh's (2003, 2013) Theory of Magnitude. In this context, a specification of the Theory of Magnitude was staked out in a processing model that stresses the pivotal role of spatial attention orienting. Implications for mental magnitude operations are discussed. Possible applications in the classroom and beyond are described.},
  subject      = {Soziale Wahrnehmung},
  language  = {en}
}
@phdthesis{Tian2019,
  author    = {Tian, Yuehui},
  title     = {Characterization of novel rhodopsins with light-regulated cGMP production or cGMP degradation},
  doi       = {10.25972/OPUS-16814},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168143},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Photoreceptors are widely occurring in almost all kingdoms of life. They mediate the first step in sensing electromagnetic radiation of different wavelength. Absorption spectra are found within the strongest radiation from the sun and absorption usually triggers downstream signaling pathways. Until now, mainly 6 classes of representative photoreceptors are known: five water-soluble proteins, of these three classes of blue light-sensitive proteins including LOV (light-oxygen-voltage), BLUF (blue-light using FAD), and cryptochrome modules with flavin (vitamin B-related) nucleotides as chromophore; while two classes of yellow and red light-sensitive proteins consist of xanthopsin and phytochrome, respectively. Lastly, as uniquely integral membrane proteins, the class of rhodopsins can usually sense over a wide absorption spectrum, ranging from ultra-violet to green and even red light. Rhodopsins can be further divided into two types, i.e., microbial (type I) and animal (type II) rhodopsins. Rhodopsins consist of the protein opsin and the covalently bound chromophore retinal (vitamin A aldehyde). In this thesis, I focus on identification and characterization of novel type I opsins with guanylyl cyclase activity from green algae and a phosphodiesterase opsin from the protist Salpingoeca rosetta. Until 2014, all known type I and II rhodopsins showed a typical structure with seven transmembrane helices (7TM), an extracellular N-terminus and a cytosolic C-terminus. The proven function of the experimentally characterized type I rhodopsins was membrane transport of ions or the coupling to a transducer which enables phototaxis via a signaling chain. A completely new class of type I rhodopsins with enzymatic activity was identified in 2014. A light-activated guanylyl cyclase opsin was discovered in the fungus Blastocladiella emersonii which was named Cyclop (Cyclase opsin) by Gao et al. (2015), after heterologous expression and rigorous in-vitro characterization. BeCyclop is the first opsin for which an 8 transmembrane helices (8TM) structure was demonstrated by Gao et al. (2015). Earlier (2004), a novel class of enzymatic rhodopsins was predicted to exist in C. reinhardtii by expressed sequence tag (EST) and genome data, however, no functional data were provided up to now. The hypothetical rhodopsin included an N-terminal opsin domain, a fused two-component system with histidinekinase and response regulator domain, and a C-terminal guanylyl cyclase (GC) domain. This suggested that there could be a biochemical signaling cascade, integrating light-induction and ATP-dependent phosphate transfer, and as output the light-sensitive cGMP production. One of my projects focused on characterizing two such opsins from the green algae Chlamydomonas reinhardtii and Volvox carteri which we then named 2c-Cyclop (two-component Cyclase opsin), Cr2c-Cyclop and Vc2c-Cyclop, respectively. My results show that both 2c-Cyclops are light-inhibited GCs. Interestingly, Cr2c-Cyclop and Vc2c-Cyclop are very sensitive to light and ATP-dependent, whereby the action spectra of Cr2c-Cyclop and Vc2c-Cyclop peak at ~540 nm and ~560 nm, respectively. More importantly, guanylyl cyclase activity is dependent on continuous phosphate transfer between histidine kinase and response regulator. However, green light can dramatically block phosphoryl group transfer and inhibit cyclase activity. Accordingly, mutation of the retinal-binding lysine in the opsin domain resulted in GC activity and lacking light-inhibition. A novel rhodopsin phosphodiesterase from the protist Salpingoeca rosetta (SrRhoPDE) was discovered in 2017. However, the previous two studies of 2017 claimed a very weak or absent light-regulation. Here I give strong evidence for light-regulation by studying the activity of SrRhoPDE, expressed in Xenopus laevis oocytes, in-vitro at different cGMP concentrations. Surprisingly, hydrolysis of cGMP shows a ~100-fold higher turnover than that of cAMP. Light can enhance substrate affinity by decreasing the Km value for cGMP from 80 μM to 13 μM, but increases the maximum turnover only by ~30\%. In addition, two key single mutants, SrRhoPDE K296A or K296M, can abolish the light-activation effect by interrupting a covalent bond of Schiff base type to the chromophore retinal. I also demonstrate that SrRhoPDE shows cytosolic N- and C- termini, most likely via an 8-TM structure. In the future, SrRhoPDE can be a potentially useful optogenetic tool for light-regulation of cGMP concentration, possibly after further improvements by genetic engineering.},
  language  = {en}
}
@phdthesis{AdelAbdelrehimMohamedSoliman2019,
  author    = {Adel Abdelrehim Mohamed Soliman, Hadya},
  title     = {Structural Equation Modeling of Factors Influencing EFL Reading comprehension: Comparative study between Egypt and Germany},
  doi       = {10.25972/OPUS-18695},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186957},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {In most foreign language learning contexts, there are only rare chance for contact with native speakers of the target language. In such a situation, reading plays an important role in language acquisition as well as in gaining cultural information about the target language and its speakers. Previous research indicated that reading in foreign language is a complex process, which is influenced by various linguistic, cognitive and affective factors. The aim of the present study was to test two structural models of the relationship between reading comprehension in native language (L1), English language (L2) reading motivation, metacognitive awareness of L2 reading strategies, and reading comprehension of English as a foreign language among the two samples. Furthermore, the current study aimed to examine the differences between Egyptian and German students in their perceived usage of reading strategies during reading English texts, as well as to explore the pattern of their motivation toward reading English texts. For this purpose, 401 students were recruited from Germany (n=200) and Egypt (n=201) to participate in the current study. In order to have information about metacognitive awareness of reading strategies, a self-report questionnaire (SORS) developed by Moktari and Sheory (2002) was used. While the L2 reading motivation variable, was measured by a reading motivation survey (L2RMQ) which was based on reviewed reading motivation research. In addition, two reading tests were administrated one to measure reading comprehension for native language (German/Arabic) and the other to measure English reading comprehension. To analyze the collected data, descriptive statistics and independent t-tests were performed. In addition, further analysis using structural equation modeling was applied to test the strength of relationships between the variables under study. The results from the current research revealed that L1 reading comprehension, whether in a German or Arabic language, had the strongest relationship with L2 reading comprehension. However, the relationship between L2 intrinsic reading motivation was not proven to be significant in either the German or Egyptian models. On the other hand, the relationship between L2 extrinsic reading motivation, metacognitive awareness of reading strategies, and L2 reading comprehension was only proven significant in the German sample. The discussion of these results along with their pedagogical implications for education and practice will be illustrated in the following study.},
  subject      = {Leseverstehen},
  language  = {en}
}
@article{BruecknerDewhurstDellermannetal.2019,
  author    = {Br{\"u}ckner, Tobias and Dewhurst, Rian D. and Dellermann, Theresa and M{\"u}ller, Marcel and Braunschweig, Holger},
  title     = {Mild synthesis of diboryldiborenes by diboration of B-B triple bonds},
  series = {Chemical Science},
  volume    = {10},
  journal   = {Chemical Science},
  doi       = {10.1039/C9SC02544H},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186306},
  pages     = {7375-7378},
  year      = {2019},
  abstract  = {A set of diboryldiborenes are prepared by the mild, catalyst-free, room-temperature diboration of the B-B triple bonds of doubly base-stabilized diborynes. Two of the product diboryldiborenes are found to be air- and water-stable in the solid state, an effect that is attributed to their high crystallinity and extreme insolubility in a wide range of solvents.},
  language  = {en}
}
@unpublished{LegarePranckeviciusBraunschweig2019,
  author    = {L{\´e}gar{\´e}, Marc-Andr{\´e} and Pranckevicius, Conor and Braunschweig, Holger},
  title     = {Metallomimetic Chemistry of Boron},
  series = {Chemical Reviews},
  journal   = {Chemical Reviews},
  doi       = {10.1021/acs.chemrev.8b00561},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186317},
  year      = {2019},
  abstract  = {The study of main-group molecules that behave and react similarly to transition-metal (TM) complexes has attracted significant interest in recent decades. Most notably, the attractive idea of replacing the all-too-often rare and costly metals from catalysis has motivated efforts to develop main-group-element-mediated reactions. Main-group elements, however, lack the electronic flexibility of TM complexes that arises from combinations of empty and filled d orbitals and that seem ideally suited to bind and activate many substrates. In this review, we look at boron, an element that despite its nonmetal nature, low atomic weight, and relative redox staticity has achieved great milestones in terms of TM-like reactivity. We show how in interelement cooperative systems, diboron molecules, and hypovalent complexes the fifth element can acquire a truly metallomimetic character. As we discuss, this character is powerfully demonstrated by the reactivity of boron-based molecules with H2, CO, alkynes, alkenes and even with N2.},
  language  = {en}
}
@phdthesis{Knapp2019,
  author    = {Knapp, Alexander Gerhard},
  title     = {Resonant Spin Flip Raman-Spectroscopy of Electrons and Manganese-Ions in the n-doped Diluted Magnetic Semiconductor (Zn,Mn)Se:Cl},
  doi       = {10.25972/OPUS-18609},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186099},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Main focus of the present dissertation was to gain new insight about the interaction between magnetic ions and the conduction band of diluted magnetic semiconductors. This interaction in magnetic semiconductors with carrier concentrations near the metal-insulator transition (MIT) in an external magnetic field is barely researched. Hence, n-doped Zn1-xMnxSe:Cl samples were studied. Resonant Raman spectroscopy was employed at an external magnetic field between 1T and 7T and a temperature of 1.5K. The resulting magnetization of the material amplifies the splitting of states with opposite spins both in the valence and the conduction band. This is known as the "giant-Zeeman-effect". In this thesis, the resonance of the electron spin flip process, i.e. the enhancement of the signal depending on the excitation energy, was used as an indicator to determine the density of states of the charge carriers. The measured resonance profiles of each sample showed a structure, which consist of two partially overlapping Gaussian curves. The analysis of the Gaussian curves revealed that their respective maxima are separated independent of the magnetic field strenght by about 5 meV, which matches the binding energy of the donor bound exciton (D0, X). A widening of the full width at half maximum of the resonance profile was observed with increasing magnetic field. A detailed analysis of this behavior showed that the donor bound exciton spin flip resonance primarily accounts for the widening for all samples with doping concentrations below the metal insulator transition. A model was proposed for the interpretation of this observation. This is based on the fundamental assumptions of a spatially random distribution of the manganese ions on the group-II sublattice of the ZnSe crystal and the finite extension of the excitons. Thus, each exciton covers an individual quantity of manganese ions, which manifest as a local manganese concentration. This local manganese concentration is normally distributed for a set of excitons and hence, the evaluation of the distribution allows the determination of exciton radii Two trends were identified for the (D0, X) radii. The radius of the bound exciton decreases with increasing carrier concentration as well as with increasing manganese concentration. The determination of the (D0, X) radii by the use of resonant spin flip Raman spectroscopy and also the observation of the behavior of the (D0, X) radius depending on the carrier concentration, was achieved for the first time. For all samples with carrier concentrations below the metal-insulator transition, the obtained (X0) radii are up to a factor of 5.9 larger than the respective (D0, X) radii. This observation is explained by the unbound character of the (X0). For the first time, such an observation could be made by Raman spectroscopy.Beside the resonance studies, the shape of the Raman signal of the electron spin flip was analyzed. Thereby an obvious asymmetry of the signal, with a clear flank to lower Raman shifts, was observed. This asymmetry is most pronounced, when the spin flip process is excited near the (D0, X) resonance. To explain this observation, a theoretical model was introduced in this thesis. Based on the asymmetry of the resonantly excited spin flip signal, it was possible to estimate the (D0, X) radii, too. At external magnetic fields between 1.25T and 7T, the obtained radii lie between 2.38nm and 2.75nm. Additionally, the asymmetry of the electron spin flip signal was observed at different excitation energies. Here it is striking that the asymmetry vanishes with increasing excitation energy. At the highest excitation energy, where the electron spin flip was still detectable, the estimated radius of the exciton is 3.92nm. Beside the observations on the electron spin flip, the resonance behavior of the spin flip processes in the d-shell of the incorporated Mn ions was studied in this thesis. This was performed for the direct Mn spin flip process as well as for the sum process of the longitudinal optical phonon with the Mn spin flip. For the Stokes and anti-Stokes direct spin flip process and for the Stokes sum process, each the resonance curve is described by considering only one resonance mechanism. In contrast, resonance for the sum process in which an anti-Stokes Mn spin flip is involved, consists of two partially overlapping resonances due to different mechanisms. A detailed analysis of this resonance profile showed that for (Zn,Mn)Se at the chosen experimental parameters, an incoming and outgoing resonance can be achieved, separated by a few meV. Hereby, at a specific excitation energy range and a high excitation power, it was possible to achieve an inversion of the anti-Stokes to Stokes intensity, because only the anti-Stokes Mn spin flip process was enhanced resonantly.},
  subject      = {Raman-Spektroskopie},
  language  = {en}
}
@phdthesis{Scheiderer2019,
  author    = {Scheiderer, Philipp},
  title     = {Spectroscopy of Prototypical Thin Film Mott Materials},
  doi       = {10.25972/OPUS-18635},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186358},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The rich phase diagram of transition metal oxides essentially roots in the many body physics arising from strong Coulomb interactions within the underlying electron system. Understanding such electronic correlation effects remains challenging for modern solid state physics, therefore experimental data is required for further progress in the field. For this reason, spectroscopic investigations of prototypical correlated materials are the scope of this thesis. The experimental methods focus on photoelectron spectroscopy, and the test materials are the correlated metal SrVO\(_3\) and the Mott insulator LaTiO\(_3\), both of which are fabricated as high quality thin films. In SrVO\(_3\) thin films, a reduction of the film thickness induces a dimensional crossover from the metallic into the Mott insulating phase. In this thesis, an extrinsic chemical contribution from a surface over-oxidation is revealed that emerges additionally to the intrinsic change of the effective bandwidth usually identified to drive the transition. The two contributions are successfully disentangled by applying a capping layer that prevents the oxidation, allowing for a clean view on the dimensional crossover in fully stoichiometric samples. Indeed, these stoichiometric layers exhibit a higher critical thickness for the onset of the metallic phase than the bare and therefore over-oxidized thin films. For LaTiO\(_3\) thin films, the tendency to over-oxidize is even stronger. An uncontrolled oxygen diffusion from the substrate into the film is found to corrupt the electronic properties of LaTiO\(_3\) layers grown on SrTiO\(_3\). The Mott insulating phase is only detected in stoichiometric films fabricated on more suitable DyScO\(_3\) substrates. In turn, it is demonstrated that a \(controlled\) incorporation of excess oxygen ions by increasing the oxygen growth pressure is an effective way of \(p\) doping the material which is used to drive the band filling induced Mott transition. Gaining control of the oxygen stoichiometry in both materials allows for a systematic investigation of correlation effects in general and of the Mott transition in particular. The investigations are realized by various photoelectron spectroscopy techniques that provide a deep insight into the electronic structure. Resonant photoemission not only gives access to the titanium and vanadium related partial density of states of the valence band features, but also shows how the corresponding signal is enhanced by tuning the photon energy to the \(L\) absorption threshold. The enhanced intensity turns out to be very helpful for probing the Fermi surface topology and band dispersions by means of angular-resolved photoemission. The resulting momentum resolved electronic structure verifies central points of the theoretical description of the Mott transition, viz. the renormalization of the band width and a constant Luttinger volume in a correlated metal as the Mott phase is approached.},
  subject      = {{\"U}bergangsmetalloxide},
  language  = {en}
}
@phdthesis{Dirimanov2019,
  author    = {Dirimanov, Stoyan Dinkov},
  title     = {Molecular Effects of Polyphenols in Experimental Type 2 Diabetes Mellitus and Metabolic Syndrome},
  doi       = {10.25972/OPUS-18570},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185701},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The growing prevalence of type 2 diabetes mellitus (T2DM) demands novel therapeutic and adjuvant strategies. Polyphenols (PPs) are plant secondary metabolites. Epidemiological studies demonstrate an inverse relationship between their increased intake and the risk of development of T2DM and cardiovascular complications. However, the PPs' mechanism of action remains largely unknown. The present work aimed to expand knowledge regarding the effects of PPs on diabetes relevant molecular targets. Pycnogenol® (PYC) is a standardized pine bark extract which consists of oligomeric and monomeric PPs. Its anti-diabetic effects have been demonstrated in clinical trials. As a part of a human study involving 20 healthy volunteers, the extract's effects on dipeptidyl peptidase IV (DPP IV) were investigated. This protease terminates the insulin secretagogue action of incretins. Its inhibition is a promising strategy in T2DM treatment. This study uncovered that PYC-intake of 100 mg daily over 14 days statistically significantly reduced DPP IV serum concentrations by 8.2 \% (n= 38, p= 0.032). Contrary to expectations, this decrease was not paralleled by a reduction in the serum DPP IV enzymatic activity. To the best of our knowledge, the present study was the first investigating the effects of PPs on DPP IV serum concentrations and activities in humans. The finding that PYC is capable of reducing DPP IV serum concentrations might be important with regard to diabetes, where DPP IV levels are increased. Screenings for PPs' in vitro effects on DPP IV activity were performed employing a purified enzyme. The effects of tested PPs (among which PYC ingredients) at a physiologically relevant concentration of 5 µM were weak (< 10 \%) and too small compared to the reference compound sitagliptin, and thus not likely to be clinically relevant. This result is in discordance with some published data, but consistent with the outcome from the present human study. In addition, fluorescence interactions with the experimental setup were registered: under certain conditions urolithin B exhibited an autofluorescence which might mask eventual inhibitory activity. Quercetin quenched the fluorescence slightly which might contribute to false positive results. No statistically significant effects of selected constituents and metabolites of PYC on the total DPP IV protein expression were observed in 3T3-L1 adipocytes. Thus, the lower DPP IV in vivo concentrations after intake of PYC cannot be explained with down-regulation of the DPP IV expression in adipocytes. Akt kinase is responsible for the transmission of insulin signals and its dysregulation is related to insulin resistance and plays an important role in development of cardiovascular complications in T2DM. Thus, the modulation of the phosphorylation status of endothelial Akt-kinase, respectively its activity, might be a promising strategy in the management of these pathologies. This work aimed to uncover the effects of PPs from different structural subclasses on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926). Short-term effects (5 - 30 min) were investigated at a concentration of 10 µM. In a pilot study two model PPs induced a moderate, but reproducible inhibition of pAkt Ser473 of 52.37 ± 21.01 \% (quercetin; p= 0.006, n= 3) and 37.79 ± 7.14 \% (resveratrol; p= 0.021, n= 4) compared to the negative control. A primary screening with Western blot analysis investigated the effects of eight compounds from different subclasses on pAkt Ser473 and Thr308 to reveal whether the observed inhibition PPs a group effect or specific to certain compounds. In addition to resveratrol and quercetin, statistically significant inhibitions of pAkt Ser473 were induced by luteolin (29.96 ± 11.06 \%, p< 0.01, n= 6) and apigenin (22.57 ± 10.30 \%, p< 0.01, n= 6). In contrast, genistein, 3,4,5-trimethoxystilbene, taxifolin and (+)-catechin caused no inhibition. A strong positive and statistically significant correlation between the mean inhibitory effects of the tested PPs on both Akt-residues Ser473 and Thr308 (r= 0.9478, p= 0.0003) was determined. A comprehensive secondary screening via ELISA involving 44 compounds from nine structural groups quantified the effects of PPs on pAkt Ser473 to uncover potential structure-activity features. The most potent inhibitors were luteolin (44.31 ± 17.95 \%), quercetin (35.71 ± 8.33 \%), urolithin A (35.28 ± 11.80 \%), apigenin (31.79 ± 6.16 \%), fisetin (28.09 ± 9.09 \%), and resveratrol (26.04 ± 5.58 \%). These effects were statistically significant (p< 0.01, n= 3 to 6). Further lead structure optimization might be based on the fact that the effects of luteolin and resveratrol also differed statistically significantly from each other (p= 0.008). To the best of our knowledge, the present study is the first to compare quantitatively the short term effects of PPs from different subclasses on pAkt in endothelial cells. Basic structure-activity relationships revealed that for flavones and flavonols the presence of a C2=C3 double bond (ring C) was essential for inhibitory activity and hydroxylation on the m- and p- positions in the ring B contributed to it. For stilbenoids, three free OH-groups appeared to be optimal. The comparison of the inhibitory potentials of ellagic acid and its microbial metabolites showed that urolithin A was statistically significantly more effective than its progenitor compound. Despite their structural similarities, the only active compound among all urolithins tested was urolithin A, hydroxylated at the C3 and C8 positions. This suggested a specific effect for urolithin A. Based on the common structural determinants and molecular geometry of the most active PPs a pharmacophore model regarding Akt-inhibition was proposed. In summary, the effects of a wide variety of PPs from diverse structural subclasses on the in vitro phosphorylation of endothelial Akt were quantitatively analyzed for the first time, the effects of previously undescribed compounds were determined and structure activity relationships were elucidated. The inhibitory potential of individual PPs might be beneficial in cases of sustained over-activation of Akt-kinase and its substrates such as S6 kinase as reported for certain T2DM-related pathological states, such as insulin resistance, endothelial dysfunction, excessive angiogenesis, vascular calcification, and insulin triggered DNA-damage. The results of the present work suggest potential molecular mechanisms of action of PP involving Akt-inhibition and DPP IV-down-regulation and thus contribute to the understanding of anti-diabetic effects of these compounds on the molecular level.},
  subject      = {Polyphenole},
  language  = {en}
}
@phdthesis{Akakpo2019,
  author    = {Akakpo, Martin Gameli},
  title     = {The influence of learner characteristics on interactions to seek and share information in e-learning: A media psychology perspective},
  doi       = {10.25972/OPUS-18593},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185934},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Research on the deployment and use of technology to assist learning has seen a significant rise over the last decades (Aparicio et al., 2017). The focus on course quality, technology, learning outcome and learner satisfaction in e-learning has led to insufficient attention by researchers to individual characteristics of learners (Cidral et al., 2017 ; Hsu et al., 2013). The current work aims to bridge this gap by investigating characteristics identified by previous works and backed by theory as influential individual differences in e-learning. These learner characteristics have been suggested as motivational factors (Edmunds et al., 2012) in decisions by learners to interact and exchange information (Luo et al., 2017). In this work e-learning is defined as interaction dependent information seeking and sharing enabled by technology. This is primarily approached from a media psychology perspective. The role of learner characteristics namely, beliefs about the source of knowledge (Schommer, 1990), learning styles (Felder \& Silverman, 1988), need for affect (Maio \& Esses, 2001), need for cognition (Cacioppo \& Petty, 1982) and power distance (Hofstede, 1980) on interactions to seek and share information in e-learning are investigated. These investigations were shaped by theory and empirical lessons as briefly mentioned in the next paragraphs. Theoretical support for investigations is derived from the technology acceptance model(TAM) by psychologist Davis (1989) and the hyper-personal model by communication scientist Walther (1996). The TAM was used to describe the influence of learner characteristics on decisions to use e-learning systems (Stantchev et al., 2014). The hyper-personal model described why computer-mediated communication thrives in e-learning (Kaye et al., 2016) and how learners interpret messages exchanged online (Hansen et al., 2015). This theoretical framework was followed by empirical reviews which justified the use of interaction and information seeking-sharing as key components of e-learning as well as the selection of learner characteristics. The reviews provided suggestions for the measurement of variables (K{\"u}hl et al., 2014) and the investigation design (Dascalau et al., 2015). Investigations were designed and implemented through surveys and quasi experiments which were used for three preliminary studies and two main studies. Samples were selected from Germany and Ghana with same variables tested in both countries. Hypotheses were tested with interaction and information seeking-sharing as dependent variables while beliefs about the source of knowledge, learning styles, need for affect, need for cognition and power distance were independent variables. Firstly, using analyses of variance, the influence of beliefs about the source of knowledge on interaction choices of learners was supported. Secondly, the role of need for cognition on interaction choices of learners was supported by results from a logistic regression. Thirdly, results from multiple linear regressions backed the influence of need for cognition and power distance on information seeking-sharing behaviour of learners. Fourthly, the relationship between need for affect and need for cognition was supported. The findings may have implications for media psychology research, theories used in this work, research on e-learning, measurement of learner characteristics and the design of e-learning platforms. The findings suggest that, the beliefs learners have about the source of knowledge, their need for cognition and their power distance can influence decisions to interact and seek or share information. The outlook from reviews and findings in this work predicts more research on learner characteristics and a corresponding intensity in the use of e-learning by individuals. It is suggested that future studies investigate the relationship between learner autonomy and power distance. Studies on inter-cultural similarities amongst e-learners in different populations are also suggested.},
  subject      = {e-learning},
  language  = {en}
}
@phdthesis{Schnells2019,
  author    = {Schnells, Vera},
  title     = {Fractional Insulators and their Parent Hamiltonians},
  doi       = {10.25972/OPUS-18561},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185616},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {In the past few years, two-dimensional quantum liquids with fractional excitations have been a topic of high interest due to their possible application in the emerging field of quantum computation and cryptography. This thesis is devoted to a deeper understanding of known and new fractional quantum Hall states and their stabilization in local models. We pursue two different paths, namely chiral spin liquids and fractionally quantized, topological phases. The chiral spin liquid is one of the few examples of spin liquids with fractional statistics. Despite its numerous promising properties, the microscopic models for this state proposed so far are all based on non-local interactions, making the experimental realization challenging. In the first part of this thesis, we present the first local parent Hamiltonians, for which the Abelian and non-Abelian chiral spin liquids are the exact and, modulo a topological degeneracy, unique ground states. We have developed a systematic approach to find an annihilation operator of the chiral spin liquid and construct from it a many-body interaction which establishes locality. For various system sizes and lattice geometries, we numerically find largely gapped eigenspectra and confirm to an accuracy of machine precision the uniqueness of the chiral spin liquid as ground state of the respective system. Our results provide an exact spin model in which fractional quantization can be studied. Topological insulators are one of the most actively studied topics in current condensed matter physics research. With the discovery of the topological insulator, one question emerged: Is there an interaction-driven set of fractionalized phases with time reversal symmetry? One intuitive approach to the theoretical construction of such a fractional topological insulator is to take the direct product of a fractional quantum Hall state and its time reversal conjugate. However, such states are well studied conceptually and do not lead to new physics, as the idea of taking a state and its mirror image together without any entanglement between the states has been well understood in the context of topological insulators. Therefore, the community has been looking for ways to implement some topological interlocking between different spin species. Yet, for all practical purposes so far, time reversal symmetry has appeared to limit the set of possible fractional states to those with no interlocking between the two spin species. In the second part of this thesis, we propose a new universality class of fractionally quantized, topologically ordered insulators, which we name "fractional insulator". Inspired by the fractional quantum Hall effect, spin liquids, and fractional Chern insulators, we develop a wave function approach to a new class of topological order in a two-dimensional crystal of spin-orbit coupled electrons. The idea is simply to allow the topological order to violate time reversal symmetry, while all locally observable quantities remain time reversal invariant. We refer to this situation as "topological time reversal symmetry breaking". Our state is based on the Halperin double layer states and can be viewed as a two-layer system of an ↑-spin and a ↓-spin sphere. The construction starts off with Laughlin states for the ↑-spin and ↓-spin electrons and an interflavor term, which creates correlations between the two layers. With a careful parameter choice, we obtain a state preserving time reversal symmetry locally, and label it the "311-state". For systems of up to six ↑-spin and six ↓-spin electrons, we manage to construct an approximate parent Hamiltonian with a physically realistic, local interaction.},
  subject      = {Spinfl{\"u}ssigkeit},
  language  = {en}
}
@phdthesis{Huestegge2019,
  author    = {Huestegge, Sujata Maya},
  title     = {Cognitive mechanisms of voice processing},
  doi       = {10.25972/OPUS-18608},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186086},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The present thesis addresses cognitive processing of voice information. Based on general theoretical concepts regarding mental processes it will differentiate between modular, abstract information processing approaches to cognition and interactive, embodied ideas of mental processing. These general concepts will then be transferred to the context of processing voice-related information in the context of parallel face-related processing streams. One central issue here is whether and to what extent cognitive voice processing can occur independently, that is, encapsulated from the simultaneous processing of visual person-related information (and vice versa). In Study 1 (Huestegge \& Raettig, in press), participants are presented with audio-visual stimuli displaying faces uttering digits. Audiovisual gender congruency was manipulated: There were male and female faces, each uttering digits with either a male or female voice (all stimuli were AV- synchronized). Participants were asked to categorize the gender of either the face or the voice by pressing one of two keys in each trial. A central result was that audio-visual gender congruency affected performance: Incongruent stimuli were categorized slower and more error-prone, suggesting a strong cross-modal interaction of the underlying visual and auditory processing routes. Additionally, the effect of incongruent visual information on auditory classification was stronger than the effect of incongruent auditory information on visual categorization, suggesting visual dominance over auditory processing in the context of gender classification. A gender congruency effect was also present under high cognitive load. Study 2 (Huestegge, Raettig, \& Huestegge, in press) utilized the same (gender-congruent and -incongruent) stimuli, but different tasks for the participants, namely categorizing the spoken digits (into odd/even or smaller/larger than 5). This should effectively direct attention away from gender information, which was no longer task-relevant. Nevertheless, congruency effects were still observed in this study. This suggests a relatively automatic processing of cross-modal gender information, which eventually affects basic speech-based information processing. Study 3 (Huestegge, subm.) focused on the ability of participants to match unfamiliar voices to (either static or dynamic) faces. One result was that participants were indeed able to match voices to faces. Moreover, there was no evidence for any performance increase when dynamic (vs. mere static) faces had to be matched to concurrent voices. The results support the idea that common person-related source information affects both vocal and facial features, and implicit corresponding knowledge appears to be used by participants to successfully complete face-voice matching. Taken together, the three studies (Huestegge, subm.; Huestegge \& Raettig, in press; Huestegge et al., in press) provided information to further develop current theories of voice processing (in the context of face processing). On a general level, the results of all three studies are not in line with an abstract, modular view of cognition, but rather lend further support to interactive, embodied accounts of mental processing.},
  subject      = {Stimme},
  language  = {en}
}
@phdthesis{Zapf2019,
  author    = {Zapf, Michael},
  title     = {Oxidische Perovskite mit Hoher Massenzahl Z: D{\"u}nnfilmdeposition und Spektroskopische Untersuchungen},
  doi       = {10.25972/OPUS-18537},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-185370},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Perovskite oxides are a very versatile material class with a large variety of outstanding physical properties. A subgroup of these compounds particularly tempting to investigate are oxides involving high-\(Z\) elements, where spin-orbit coupling is expected to give rise to new intriguing phases and potential application-relevant functionalities. This thesis deals with the preparation and characterization of two representatives of high-\(Z\) oxide sample systems based on KTaO\(_3\) and BaBiO\(_3\). KTaO\(_3\) is a band insulator with an electronic valence configuration of Ta 5\(d\)\(^0\) . It is shown that by pulsed laser deposition of a disordered LaAlO\(_3\) film on the KTaO\(_3\)(001) surface, through the creation of oxygen vacancies, a Ta 5\(d\)\(^{0+\(\delta\)}\) state is obtained in the upmost crystal layers of the substrate. In consequence a quasi two dimensional electron system (q2DES) with large spin-orbit coupling emerges at the heterointerface. Measurements of the Hall effect establish sheet carrier densities in the range of 0.1-1.2 10\(^{14}\) cm\(^2\), which can be controlled by the applied oxygen background pressure during deposition and the LaAlO\(_3\) film thickness. When compared to the prototypical oxide q2DESs based on SrTiO\(_3\) crystals, the investigated system exhibits exceptionally large carrier mobilities of up to 30 cm\(^2\)/Vs (7000 cm\(^2\)/Vs) at room temperature (below 10 K). Through a depth profiling by photoemission spectra of the Ta 4\(f\) core level it is shown that the majority of the Ta 5\(d\)\(^0\) charge carriers, consisting of mobile and localized electrons, is situated within 4 nm from the interface at low temperatures. Furthermore, the momentum-resolved electronic structure of the q2DES \(buried\) underneath the LaAlO\(_3\) film is probed by means of hard X-ray angle-resolved photoelectron spectroscopy. It is inferred that, due to a strong confinement potential of the electrons, the band structure of the system is altered compared to \(n\)-doped bulk KTO. Despite the constraint of the electron movement along one direction, the Fermi surface exhibits a clear three dimensional momentum dependence, which is related to a depth extension of the conduction channels of at least 1 nm. The second material, BaBiO\(_3\), is a charge-ordered insulator, which has recently been predicted to emerge as a large-gap topological insulator upon \(n\)-doping. This study reports on the thin film growth of pristine BaBiO\(_3\) on Nb:SrTiO\(_3\)(001) substrates by means of pulsed laser deposition. The mechanism is identified that facilitates the development of epitaxial order in the heterostructure despite the presence of an extraordinary large lattice mismatch of 12 \%. At the heterointerface, a structurally modified layer of about 1.7 nm thickness is formed that gradually relieves the in-plane strain and serves as the foundation of a relaxed BBO film. The thereupon formed lattice orders laterally in registry with the substrate with the orientation BaBiO\(_3\)(001)||SrTiO\(_3\)(001) by so-called domain matching, where 8 to 9 BaBiO\(_3\) unit cells align with 9 to 10 unit cells of the substrate. Through the optimization of the deposition conditions in regard to the cation stoichiometry and the structural lattice quality, BaBiO\(_3\) thin films with bulk-like electronic properties are obtained, as is inferred from a comparison of valence band spectra with density functional theory calculations. Finally, a spectroscopic survey of BaBiO\(_3\) samples of various thicknesses resolves that a recently discovered film thickness-controlled phase transition in BaBiO\(_3\) thin films can be traced back to the structural and concurrent stoichiometric modifications occuring in the initially formed lattice on top of the SrTiO\(_3\) substrate rather than being purely driven by the smaller spatial extent of the BBO lattice.},
  subject      = {Perowskit},
  language  = {en}
}
@unpublished{EnglertStoyArrowsmithetal.2019,
  author    = {Englert, Lukas and Stoy, Andreas and Arrowsmith, Merle and M{\"u}ssig, Jonas H. and Thaler, Melanie and Deißenberger, Andrea and H{\"a}fner, Alena and B{\"o}hnke, Julian and Hupp, Florian and Seufert, Jens and Mies, Jan and Damme, Alexander and Dellermann, Theresa and Hammond, Kai and Kupfer, Thomas and Radacki, Krzysztof and Thiess, Torsten and Braunschweig, Holger},
  title     = {Stable Lewis Base Adducts of Tetrahalodiboranes: Synthetic Methods and Structural Diversity},
  series = {Chemistry - A European Journal},
  journal   = {Chemistry - A European Journal},
  doi       = {10.1002/chem.201901437},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184888},
  year      = {2019},
  abstract  = {A series of 22 new bis(phosphine), bis(carbene) and bis(isonitrile) tetrahalodiborane adducts has been synthesized, either by direct adduct formation with highly sensitive B2X4 precursors (X = Cl, Br, I) or by ligand exchange at stable B2X4(SMe2)2 precursors (X = Cl, Br) with labile dimethylsulfide ligands. The isolated compounds have been fully characterized using NMR spectroscopic, (C,H,N)- elemental and, for 20 of these compounds, X-ray crystallographic analysis, revealing an unexpected variation in the bonding motifs. Besides the classical B2X4L2 diborane(6) adducts, some of the more sterically demanding carbene ligands induce a halide displacement leading to the first halide-bridged monocationic diboron species, [B2X3L2]A (A = BCl4, Br, I). Furthermore, low-temperature 1:1 reactions of B2Cl4 with sterically demanding N-heterocyclic carbenes led to the formation of kinetically unstable mono-adducts, one of which was structurally characterized. A comparison of the NMR and structural data of new and literature-known bis-adducts shows several trends pertaining to the nature of the halides and the stereoelectronic properties of the Lewis bases employed.},
  language  = {en}
}
@unpublished{BruecknerArrowsmithHessetal.2019,
  author    = {Br{\"u}ckner, Tobias and Arrowsmith, Merle and Heß, Merlin and Hammond, Kai and M{\"u}ller, Marcel and Braunschweig, Holger},
  title     = {Synthesis of fused B,N-heterocycles by alkyne cleavage, NHC ring-expansion and C-H activation at a diboryne},
  series = {Chemical Communications},
  journal   = {Chemical Communications},
  doi       = {10.1039/C9CC02657F},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184899},
  year      = {2019},
  abstract  = {The addition of alkynes to a staturated N-heterocyclic carbene (NHC)-supported diboryne results in spontaneous cycloaddition, with complete B≡B and C≡C triple bond cleavage, NHC ring- expansion and activation of a variety of C-H bonds, leading to the formation of complex mixtures of fused B,N-heterocycles.},
  language  = {en}
}
@unpublished{ArrowsmithDoemlingSchmidtetal.2019,
  author    = {Arrowsmith, Merle and D{\"o}mling, Michael and Schmidt, Uwe and Werner, Luis and Castro, Abril C. and Jim{\´e}nez-Halla, J. Oscar C. and M{\"u}ssig, Jonas and Prieschl, Dominic and Braunschweig, Holger},
  title     = {Spontaneous trans-Selective Transfer Hydrogenation of Apolar B=B Double Bonds},
  series = {Angewandte Chemie, International Edition},
  journal   = {Angewandte Chemie, International Edition},
  doi       = {10.1002/anie.201902656},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184874},
  year      = {2019},
  abstract  = {The transfer hydrogenation of NHC-supported diborenes with dimethylamine borane proceeds with high selectivity for the trans-1,2-dihydrodiboranes(6). DFT calculations suggest a stepwise proton-first-hydride-second reaction mechanism via an intermediate μ-hydrodiboronium dimethylaminoborate ion pair.},
  language  = {en}
}
@phdthesis{Aboagye2019,
  author    = {Aboagye, Benjamin},
  title     = {Behavioral and physiologic consequences of inducible inactivation of the \(Tryptophan\) \(hydroxylase\) 2 gene in interaction with early-life adversity},
  doi       = {10.25972/OPUS-17358},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173581},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Disruptions in brain serotonin (5-hydroxytryptamine, 5-HT) signaling pathways have been associated with etiology and pathogenesis of various neuropsychiatric disorders, but specific neural mechanisms of 5-HT function are yet to be fully elucidated. Tryptophan hydroxylase 2 (TPH2) is the rate-limiting enzyme for brain 5-HT synthesis. Therefore, in this study a tamoxifen (Tam)-inducible cre-mediated conditional gene (Tph2) knockout in adult mouse brain (Tph2icKO) has been established to decipher the specific role of brain 5-HT in the regulation of behavior in adulthood. Immunohistochemistry and high-performance liquid chromatography (HPLC) were used first to test the efficacy of Tam-inducible inactivation of Tph2 and consequential reduction of 5-HT in adult mouse brain. Tam treatment resulted in ≥90\% reduction in the number of 5-HT immuno-reactive cells in the anterior raphe nuclei. HPLC revealed a significant reduction in concentration of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) in selected brain regions of Tph2icKO, indicating the effectiveness of the protocol used. Second, standard behavioral tests were used to assess whether reduced brain 5-HT concentrations could alter anxiety-, fear- and depressive-like behavior in mice. No altered anxiety- and depressive-like behaviors were observed in Tph2icKO compared to control mice (Tph2CON) in all indices measured, but Tph2icKO mice exhibited intense and sustained freezing during context-dependent fear memory retrieval. Tph2icKO mice also exhibited locomotor hyperactivity in the aversive environments, such as the open field, and consumed more food and fluid than Tph2CON mice. Lastly, the combined effect of maternal separation (MS) stress and adult brain 5-HT depletion on behavior was assessed in male and female mice. Here, MS stress, 5-HT depletion and their interaction elicited anxiety-like behavior in a sex-dependent manner. MS reduced exploratory behavior in both male and female mice. Reduced 5-HT enhanced anxiety in female, but not in male mice. Furthermore, expression of genes related to the 5-HT system and emotionality (Tph2, Htr1a, Htr2a, Maoa and Avpr1a) was assessed by performing a quantitative real-time PCR. In Tph2icKO mice there was a reduction in expression of Tph2 in the raphe nuclei of both male and female mice. Interaction between MS stress and 5-HT deficiency was detected showing increased Htr2a and Maoa expression in raphe and hippocampus respectively of female mice. In male mice, MS stress and 5-HT depletion interaction effects reduced Avpr1a expression in raphe, while the expression of Htr1a, Htr2a and Maoa was differentially altered by 5-HT depletion and MS in various brain regions.},
  subject      = {Anxiety},
  language  = {en}
}
@phdthesis{Wermser2019,
  author    = {Wermser, Charlotte},
  title     = {Morphology, regulation and interstrain interactions in a new macrocolony biofilm model of the human pathogen \(Staphylococcus\) \(aureus\)},
  doi       = {10.25972/OPUS-16593},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165931},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {The role of multicellularity as the predominant microbial lifestyle has been affirmed by studies on the genetic regulation of biofilms and the conditions driving their formation. Biofilms are of prime importance for the pathology of chronic infections of the opportunistic human pathogen Staphylococcus aureus. The recent development of a macrocolony biofilm model in S. aureus opened new opportunities to study evolution and physiological specialization in biofilm communities in this organism. In the macrocolony biofilm model, bacteria form complex aggregates with a sophisticated spatial organization on the micro- and macroscale. The central positive and negative regulators of this organization in S. aureus are the alternative sigma factor σB and the quorum sensing system Agr, respectively. Nevertheless, nothing is known on additional factors controlling the macrocolony morphogenesis. In this work, the genome of S. aureus was screened for novel factors that are required for the development of the macrocolony architecture. A central role for basic metabolic pathways was demonstrated in this context as the macrocolony architecture was strongly altered by the disruption of nucleotide and carbohydrate synthesis. Environmental signals further modulate macrocolony morphogenesis as illustrated by the role of an oxygen-sensitive gene regulator, which is required for the formation of complex surface structures. A further application of the macrocolony biofilm model was demonstrated in the study of interstrain interactions. The integrity of macrocolony communities was macroscopically visibly disturbed by competitive interactions between clinical isolates of S. aureus. The results of this work contribute to the characterization of the macrocolony biofilm model and improve our understanding of developmental processes relevant in staphylococcal infections. The identification of anti-biofilm effects exercised through competitive interactions could lead to the design of novel antimicrobial strategies targeting multicellular bacterial communities.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Beck2019,
  author    = {Beck, Sebastian},
  title     = {Using optogenetics to influence the circadian clock of \(Drosophila\) \(melanogaster\)},
  doi       = {10.25972/OPUS-18495},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-184952},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Almost all life forms on earth have adapted to the most impactful and most predictable recurring change in environmental condition, the cycle of day and night, caused by the axial rotation of the planet. As a result many animals have evolved intricate endogenous clocks, which adapt and synchronize the organisms' physiology, metabolism and behaviour to the daily change in environmental conditions. The scientific field researching these endogenous clocks is called chronobiology and has steadily grown in size, scope and relevance since the works of the earliest pioneers in the 1960s. The number one model organism for the research of circadian clocks is the fruit fly, Drosophila melanogaster, whose clock serves as the entry point to understanding the basic inner workings of such an intricately constructed endogenous timekeeping system. In this thesis it was attempted to combine the research on the circadian clock with the techniques of optogenetics, a fairly new scientific field, launched by the discovery of Channelrhodopsin 2 just over 15 years ago. Channelrhodopsin 2 is a light-gated ion channel found in the green alga Chlamydomonas reinhardtii. In optogenetics, researches use these light-gated ion channels like Channelrhodopsin 2 by heterologously expressing them in cells and tissues of other organisms, which can then be stimulated by the application of light. This is most useful when studying neurons, as these channels provide an almost non-invasive tool to depolarize the neuronal plasma membranes at will. The goal of this thesis was to develop an optogenetic tool, which would be able to influence and phase shift the circadian clock of Drosophila melanogaster upon illumination. A phase shift is the adaptive response of the circadian clock to an outside stimulus that signals a change in the environmental light cycle. An optogenetic tool, able to influence and phase shift the circadian clock predictably and reliably, would open up many new ways and methods of researching the neuronal network of the clock and which neurons communicate to what extent, ultimately synchronizing the network. The first optogenetic tool to be tested in the circadian clock of Drosophila melanogaster was ChR2-XXL, a channelrhodopsin variant with dramatically increased expression levels and photocurrents combined with a prolonged open state. The specific expression of ChR2-XXL and of later constructs was facilitated by deploying the three different clock-specific GAL4-driver lines, clk856-gal4, pdf-gal4 and mai179-gal4. Although ChR2-XXL was shown to be highly effective at depolarizing neurons, these stimulations proved to be unable to significantly phase shift the circadian clock of Drosophila. The second series of experiments was conducted with the conceptually novel optogenetic tools Olf-bPAC and SthK-bPAC, which respectively combine a cyclic nucleotide-gated ion channel (Olf and SthK) with the light-activated adenylyl-cyclase bPAC. These tools proved to be quite useful when expressed in the motor neurons of instar-3 larvae of Drosophila, paralyzing the larvae upon illumination, as well as affecting body length. This way, these new tools could be precisely characterized, spawning a successfully published research paper, centered around their electrophysiological characterization and their applicability in model organisms like Drosophila. In the circadian clock however, these tools caused substantial damage, producing severe arrhythmicity and anomalies in neuronal development. Using a temperature-sensitive GAL80-line to delay the expression until after the flies had eclosed, yielded no positive results either. The last series of experiments saw the use of another new series of optogenetic tools, modelled after the Olf-bPAC, with bPAC swapped out for CyclOp, a membrane-bound guanylyl-cyclase, coupled with less potent versions of the Olf. This final attempt however also ended up being unsuccessful. While these tools could efficiently depolarize neuronal membranes upon illumination, they were ultimately unable to stimulate the circadian clock in way that would cause it to phase shift. Taken together, these mostly negative results indicate that an optogenetic manipulation of the circadian clock of Drosophila melanogaster is an extremely challenging subject. As light already constitutes the most impactful environmental factor on the circadian clock, the combination of chronobiology with optogenetics demands the parameters of the conducted experiments to be tuned with an extremely high degree of precision, if one hopes to receive positive results from these types of experiments at all.},
  subject      = {Chronobiologie},
  language  = {en}
}