@article{LiuHuNordbecketal.2016, author = {Liu, Dan and Hu, Kai and Nordbeck, Peter and Ertl, Georg and St{\"o}rk, Stefan and Weidemann, Frank}, title = {Longitudinal strain bull's eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy}, series = {European Journal of Medical Research}, volume = {21}, journal = {European Journal of Medical Research}, number = {21}, doi = {10.1186/s40001-016-0216-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146373}, year = {2016}, abstract = {Despite substantial advances in the imaging techniques and pathophysiological understanding over the last decades, identification of the underlying causes of left ventricular hypertrophy by means of echocardiographic examination remains a challenge in current clinical practice. The longitudinal strain bull's eye plot derived from 2D speckle tracking imaging offers an intuitive visual overview of the global and regional left ventricular myocardial function in a single diagram. The bull's eye mapping is clinically feasible and the plot patterns could provide clues to the etiology of cardiomyopathies. The present review summarizes the longitudinal strain, bull's eye plot features in patients with various cardiomyopathies and concentric left ventricular hypertrophy and the bull's eye plot features might serve as one of the cardiac workup steps on evaluating patients with left ventricular hypertrophy.}, language = {en} } @article{WestermaierLinsenmannHomolaetal.2016, author = {Westermaier, Thomas and Linsenmann, Thomas and Homola, Gy{\"o}rgy A. and Loehr, Mario and Stetter, Christian and Willner, Nadine and Ernestus, Ralf-Ingo and Soymosi, Laszlo and Vince, Giles H.}, title = {3D rotational fluoroscopy for intraoperative clip control in patients with intracranial aneurysms - assessment of feasibility and image quality}, series = {BMC Medical Imaging}, volume = {16}, journal = {BMC Medical Imaging}, number = {30}, doi = {10.1186/s12880-016-0133-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146381}, year = {2016}, abstract = {Background Mobile 3D fluoroscopes have become increasingly available in neurosurgical operating rooms. In this series, the image quality and value of intraoperative 3D fluoroscopy with intravenous contrast agent for the evaluation of aneurysm occlusion and vessel patency after clip placement was assessed in patients who underwent surgery for intracranial aneurysms. Materials and methods Twelve patients were included in this retrospective analysis. Prior to surgery, a 360° rotational fluoroscopy scan was performed without contrast agent followed by another scan with 50 ml of intravenous iodine contrast agent. The image files of both scans were transferred to an Apple PowerMac® workstation, subtracted and reconstructed using OsiriX® free software. The procedure was repeated after clip placement. Both image sets were compared for assessment of aneurysm occlusion and vessel patency. Results Image acquisition and contrast administration caused no adverse effects. Image quality was sufficient to follow the patency of the vessels distal to the clip. Metal artifacts reduce the assessability of the immediate vicinity of the clip. Precise image subtraction and post-processing can reduce metal artifacts and make the clip-site assessable and depict larger neck-remnants. Conclusion This technique quickly supplies images at adequate quality to evaluate distal vessel patency after aneurysm clipping. Significant aneurysm remnants may be depicted as well. As it does not require visual control of all vessels that are supposed to be evaluated intraoperatively, this technique may be complementary to other intraoperative tools like indocyanine green videoangiography and micro-Doppler, especially for the assessment of larger aneurysms. At the momentary state of this technology, it cannot replace postoperative conventional angiography. However, 3D fluoroscopy and image post-processing are young technologies. Further technical developments are likely to result in improved image quality.}, language = {en} } @article{WolfBraunHainingetal.2016, author = {Wolf, Karen and Braun, Attila and Haining, Elizabeth J. and Tseng, Yu-Lun and Kraft, Peter and Schuhmann, Michael K. and Gotru, Sanjeev K. and Chen, Wenchun and Hermanns, Heike M. and Stoll, Guido and Lesch, Klaus-Peter and Nieswandt, Bernhard}, title = {Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice}, series = {PLoS One}, volume = {11}, journal = {PLoS One}, number = {1}, doi = {10.1371/journal.pone.0147664}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146399}, pages = {e0147664}, year = {2016}, abstract = {Background Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. Objective To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt\(^{-/-}\)) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. Results In 5Htt\(^{-/-}\) platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca\(^{2+}\) entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt\(^{-/-}\) platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt\(^{-/-}\) mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt\(^{-/-}\) mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. Conclusion Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization.}, language = {en} } @phdthesis{Schmitz2016, author = {Schmitz, Tobias}, title = {Functional coatings by physical vapor deposition (PVD) for biomedical applications}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144825}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Metals are the most used materials for implant devices, especially in orthopedics, but despite their long history of application issues such as material failure through wear and corrosion remain unsolved leading to a certain number of revision surgeries. Apart from the problems associated with insufficient material properties, another serious issue is an implant associated infection due to the formation of a biofilm on the surface of the material after implantation. Thus, improvements in implant technology are demanded, especially since there is a projected rise of implants needed in the future. Surface modification methods such as physical vapour deposition (PVD), oxygen diffusion hardening and electrochemical anodization have shown to be efficient methods to improve the surfaces of metallic bulk materials regarding biomedical issues. This thesis was focused on the development of functional PVD coatings that are suitable for further treatment with surface modification techniques originally developed for bulk metals. The aim was to precisely adjust the surface properties of the implant according to the targeted application to prevent possible failure mechanisms such as coating delamination, wear or the occurrence of post-operative infections. Initially,  tantalum layers with approx 5 µm thickness were deposited at elevated substrate temperatures on cp Ti by RF magnetron sputtering. Due to the high affinity of tantalum to oxygen, these coatings are known to provide a self healing capacity since the rapid oxide formation is known to close surface cracks. Here, the work aimed to reduce the abrupt change of mechanical properties between the hard and brittle coating and the ductile substrate by creating an oxygen diffusion zone. It was found that the hardness and adhesion could be significantly increased when the coatings were treated afterwards by oxygen diffusion hardening in a two step process. Firstly, the surface was oxidized at a pressure of 6.7•10-3 mbar at 350 450 °C, followed by 1-2 h annealing in oxygen-free atmosphere at the same temperature leading to a diffusion of oxygen atoms into deeper parts of the substrate as proved by X-ray diffraction (XRD) analysis. The hereby caused mechanical stress in the crystal lattice led to an increase in Vickers hardness of the Ta layers from 570 HV to over 900 HV. Investigations into the adhesion of oxygen diffusion treated samples by Rockwell measurements demonstrated an increase of critical force for coating delamination from 12 N for untreated samples up to 25 N for diffusion treated samples. In a second approach, the development of modular targets aimed to produce functional coatings by metallic doping of titanium with biologically active agents. This was demonstrated by the fabrication of antimicrobial Ti(Ag) coatings using a single magnetron sputtering source equipped with a titanium target containing implemented silver modules under variation of bias voltage and substrate temperature. The deposition of both Ti and Ag was confirmed by X-ray diffraction and a clear correlation between the applied sputtering parameters and the silver content of the coatings was demonstrated by ICP-MS and EDX. Surface-sensitive XPS measurements revealed that higher substrate temperatures led to an accumulation of Ag in the near-surface region, while the application of a bias voltage had the opposite effect. SEM and AFM microscopy revealed that substrate heating during film deposition supported the formation of even and dense surface layers with small roughness values, which could even be enforced by applying a substrate bias voltage. Additional elution measurements using ICP-MS showed that the release kinetics depended on the amount of silver located at the film surface and hence could be tailored by variation of the sputter parameters. In a final step, the applied Ti and Ti(Ag) coatings deposited on cp Ti, stainless steel (316L) and glass substrates were subsequently nanostructured using a self-ordering process induced by electrochemical anodization in aqueous fluoride containing electrolytes. SEM analysis showed that nanotube arrays could be grown from the Ti and Ti(Ag) coatings deposited at elevated temperatures on any substrate, whereby no influence of the substrate on nanotube morphology could be observed. EDX measurements indicated that the anodization process led to the selective etching of Ti from Ti(Ag) coating. Further experiments on coatings deposited on glass surfaces revealed that moderate substrate temperatures during deposition resulting in smooth Ti layers as determined by AFM measurements, are favorable for the generation of highly ordered nanotube arrays. Such arrays exhibited superhydrophilic behavior as proved by contact angle measurements. XRD analysis revealed that the nanostructured coatings were amorphous after anodization but could be crystallized to anatase structure by thermal treatment at temperatures of 450°C.}, subject = {PVD-Verfahren}, language = {en} } @phdthesis{Cicova2016, author = {Cicova, Zdenka}, title = {Characterization of a novel putative factor involved in host adaptation in Trypanosoma brucei}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142462}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level in a systematic way. However, a detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor (Tb927.11.2400) identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38\% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin like (TbFlabarinL) and demonstrate that it is a result of a gene duplication event, which occurred in African trypanosomes. TbFlabarinL is not essential for growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated a TbFlabarinL-specific antibody and showed that it localizes in the flagellum. The co-immunoprecipitation experiment together with a biochemical cell fractionation indicated a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod.}, subject = {Trypanosoma brucei}, language = {en} } @unpublished{ArrowsmithBoehnkeBraunschweigetal.2016, author = {Arrowsmith, Merle and B{\"o}hnke, Julian and Braunschweig, Holger and Celik, Mehmet and Claes, Christina and Ewing, William and Krummenacher, Ivo and Lubitz, Katharina and Schneider, Christoph}, title = {Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition}, doi = {10.1002/anie.201602384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142500}, pages = {4}, year = {2016}, abstract = {Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaro- matic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient con- ditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6p-aromatic dibora- benzene compound, a 2 p-aromatic triplet biradical 1,3-dibor- ete, and a phosphine-stabilized 2 p-homoaromatic 1,3-dihydro- 1,3-diborete. DFT calculations suggest that all three com- pounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6H6 and C4H42+, and homoaromatic C4H5+.}, subject = {Diborane}, language = {en} } @phdthesis{Kupper2016, author = {Kupper, Maria}, title = {The immune transcriptome and proteome of the ant Camponotus floridanus and vertical transmission of its bacterial endosymbiont Blochmannia floridanus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142534}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {The evolutionary success of insects is believed to be at least partially facilitated by symbioses between insects and prokaryotes. Bacterial endosymbionts confer various fitness advantages to their hosts, for example by providing nutrients lacking from the insects' diet thereby enabling the inhabitation of new ecological niches. The Florida carpenter ant Camponotus floridanus harbours endosymbiotic bacteria of the genus Blochmannia. These primary endosymbionts mainly reside in the cytoplasm of bacteriocytes, specialised cells interspersed into the midgut tissue, but they were also found in oocytes which allows their vertical transmission. The social lifestyle of C. floridanus may facilitate the rapid spread of infections amongst genetically closely related animals living in huge colonies. Therefore, the ants require an immune system to efficiently combat infections while maintaining a "chronic" infection with their endosymbionts. In order to investigate the immune repertoire of the ants, the Illumina sequencing method was used. The previously published genome sequence of C. floridanus was functionally re-annotated and 0.53\% of C. floridanus proteins were assigned to the gene ontology (GO) term subcategory "immune system process". Based on homology analyses, genes encoding 510 proteins with possible immune function were identified. These genes are involved in microbial recognition and immune signalling pathways but also in cellular defence mechanisms, such as phagocytosis and melanisation. The components of the major signalling pathways appear to be highly conserved and the analysis revealed an overall broad immune repertoire of the ants though the number of identified genes encoding pattern recognition receptors (PRRs) and antimicrobial peptides (AMPs) is comparatively low. Besides three genes coding for homologs of thioester-containing proteins (TEPs), which have been shown to act as opsonins promoting phagocytosis in other insects, six genes encoding the AMPs defesin-1 and defensin-2, hymenoptaecin, two tachystatin-like peptides and one crustin-like peptide are present in the ant genome. Although the low number of known AMPs in comparison to 13 AMPs in the honey bee Apis mellifera and 46 AMPs in the wasp Nasonia vitripennis may indicate a less potent immune system, measures summarised as external or social immunity may enhance the immune repertoire of C. floridanus, as it was discussed for other social insects. Also, the hymenoptaecin multipeptide precursor protein may be processed to yield seven possibly bioactive peptides. In this work, two hymenoptaecin derived peptides were heterologously expressed and purified. The preliminary antimicrobial activity assays indicate varying bacteriostatic effects of different hymenoptaecin derived peptides against Escherichia coli D31 and Staphylococcus aureus which suggests a functional amplification of the immune response further increasing the antimicrobial potency of the ants. Furthermore, 257 genes were differentially expressed upon immune challenge of C. floridanus and most of the immune genes showing differential expression are involved in recognition of microbes or encode immune effectors rather than signalling components. Additionally, genes coding for proteins involved in storage and metabolism were downregulated upon immune challenge suggesting a trade-off between two energy-intensive processes in order to enhance effectiveness of the immune response. The analysis of gene expression via qRT-PCR was used for validation of the transcriptome data and revealed stage-specific immune gene regulation. Though the same tendencies of regulation were observed in larvae and adults, expression of several immune-related genes was generally more strongly induced in larvae. Immune gene expression levels depending on the developmental stage of C. floridanus are in agreement with observations in other insects and might suggest that animals from different stages revert to individual combinations of external and internal immunity upon infection. The haemolymph proteome of immune-challenged ants further established the immune-relevance of several proteins involved in classical immune signalling pathways, e.g. PRRs, extracellularly active proteases of the Toll signalling pathway and effector molecules such as AMPs, lysozymes and TEPs. Additionally, non-canonical proteins with putative immune function were enriched in immune-challenged haemolymph, e.g. Vitellogenins, NPC2-like proteins and Hemocytin. As known from previous studies, septic wounding also leads to the upregulation of genes involved in stress responses. In the haemolymph, proteins implicated in protein stabilisation and in the protection against oxidative stress and insecticides were enriched upon immune challenge. In order to identify additional putative immune effectors, haemolymph peptide samples from immune-challenged larvae and adults were analysed. The analysis in this work focussed on the identification of putative peptides produced via the secretory pathway as previously described for neuropeptides of C. floridanus. 567 regulated peptides derived from 39 proteins were identified in the larval haemolymph, whereas 342 regulated peptides derived from 13 proteins were found in the adult haemolymph. Most of the peptides are derived from hymenoptaecin or from putative uncharacterised proteins. One haemolymph peptide of immune-challenged larvae comprises the complete amino acid sequence of a predicted peptide derived from a Vitellogenin. Though the identified peptide lacks similarities to any known immune-related peptide, it is a suitable candidate for further functional analysis. To establish a stable infection with the endosymbionts, the bacteria have to be transmitted to the next generation of the ants. The vertical transmission of B. floridanus is guaranteed by bacterial infestation of oocytes. This work presents the first comprehensive and detailed description of the localisation of the bacterial endosymbionts in C. floridanus ovaries during oogenesis. Whereas the most apical part of the germarium, which contains the germ-line stem cells, is not infected by the bacteria, small somatic cells in the outer layers of each ovariole were found to be infected in the lower germarium. Only with the beginning of cystocyte differentiation, endosymbionts are exclusively transported from follicle cells into the growing oocytes, while nurse cells were never infected with B. floridanus. This infestation of the oocytes by bacteria very likely involves exocytosis-endocytosis processes between follicle cells and the oocytes. A previous study suggested a down-modulation of the immune response in the midgut tissue which may promote endosymbiont tolerance. Therefore, the expression of several potentially relevant immune genes was analysed in the ovarial tissue by qRT-PCR. The relatively low expression of genes involved in Toll and IMD signalling, and the high expression of genes encoding negative immune regulators, such as PGRP-LB, PGRP-SC2, and tollip, strongly suggest that a down-modulation of the immune response may also facilitate endosymbiont tolerance in the ovaries and thereby contribute to their vertical transmission. Overall, the present thesis improves the knowledge about the immune repertoire of C. floridanus and provides new candidates for further functional analyses. Moreover, the involvement of the host immune system in maintaining a "chronic" infection with symbiotic bacteria was confirmed and extended to the ovaries.}, subject = {Camponotus floridanus}, language = {en} } @phdthesis{Wanzek2016, author = {Wanzek, Katharina}, title = {The investigation of the function of repair proteins at G-quadruplex structures in \(Saccharomyces\) \(cerevisiae\) revealed that Mms1 promotes genome stability}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142547}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {G-quadruplex structures are highly stable alternative DNA structures that can, when not properly regulated, impede replication fork progression and cause genome instability (Castillo Bosch et al, 2014; Crabbe et al, 2004; Koole et al, 2014; Kruisselbrink et al, 2008; London et al, 2008; Lopes et al, 2011; Paeschke et al, 2013; Paeschke et al, 2011; Piazza et al, 2015; Piazza et al, 2010; Piazza et al, 2012; Ribeyre et al, 2009; Sabouri et al, 2014; Sarkies et al, 2012; Sarkies et al, 2010; Schiavone et al, 2014; Wu \& Spies, 2016; Zimmer et al, 2016). The aim of this thesis was to identify novel G-quadruplex interacting proteins in Saccharomyces cerevisiae and to unravel their regulatory function at these structures to maintain genome integrity. Mms1 and Rtt101 were identified as G-quadruplex binding proteins in vitro via a pull-down experiment with subsequent mass spectrometry analysis. Rtt101, Mms1 and Mms22, which are all components of an ubiquitin ligase (Rtt101Mms1/Mms22), are important for the progression of the replication fork following fork stalling (Luke et al, 2006; Vaisica et al, 2011; Zaidi et al, 2008). The in vivo binding of endogenously tagged Mms1 to its target regions was analyzed genome-wide using chromatin-immunoprecipitation followed by deep-sequencing. Interestingly, Mms1 bound independently of Mms22 and Rtt101 to G-rich regions that have the potential to form G-quadruplex structures. In vitro, formation of G-quadruplex structures could be shown for the G-rich regions Mms1 bound to. This binding was observed throughout the cell cycle. Furthermore, the deletion of MMS1 caused replication fork stalling as evidenced by increased association of DNA Polymerase 2 at Mms1 dependent sites. A gross chromosomal rearrangement assay revealed that deletion of MMS1 results in a significantly increased genome instability at G-quadruplex motifs compared to G-rich or non-G-rich regions. Additionally, binding of the helicase Pif1, which unwinds G4 structures in vitro (Paeschke et al, 2013; Ribeyre et al, 2009; Sanders, 2010; Wallgren et al, 2016), to Mms1 binding sites was reduced in mms1 cells. The data presented in this thesis, together with published data, suggests a novel mechanistic model in which Mms1 binds to G-quadruplex structures and enables Pif1 association. This allows for replication fork progression and genome integrity.}, subject = {Quadruplex-DNS}, language = {en} } @phdthesis{Maurus2016, author = {Maurus, Katja}, title = {Melanoma Maintenance by the AP1 Transcription Factor FOSL1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142995}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Identifying novel driver genes in cancer remains a crucial step towards development of new therapeutic approaches and the basic understanding of the disease. This work describes the impact of the AP1 transcription activator component FOSL1 on melanoma maintenance. FOSL1 is strongly upregulated during the progression of melanoma and the protein abundance is highest in metastases. I found that the regulation of FOSL1 is strongly dependent on ERK1/2- and PI3K- signaling, two pathways frequently activated in melanoma. Moreover, the involvement of p53 in FOSL1 regulation in melanoma was investigated. Elevated levels of the tumor suppressor led to decreased FOSL1 protein levels in a miR34a/miR34c- dependent manner. The benefit of elevated FOSL1 amounts in human melanoma cell lines was analyzed by overexpression of FOSL1 in cell lines with low endogenous FOSL1 levels. Enhanced levels of FOSL1 had several pro-tumorigenic effects in human melanoma cell lines. Besides increased proliferation and migration rates, FOSL1 overexpression induced the colony forming ability of the cells. Additionally, FOSL1 was necessary for anchorage independent growth in 3D cell cultures. Microarray analyses revealed novel downstream effectors of FOSL1. On the one hand, FOSL1 was able to induce the transcription of different neuron-related genes, such as NEFL, NRP1 and TUBB3. On the other hand, FOSL1 influenced the transcription of DCT, a melanocyte specific gene, in dependence of the differentiation of the melanoma cell line, indicating dedifferentiation. Furthermore, FOSL1 induced the transcription of HMGA1, a chromatin remodeling protein with reprogramming ability, which is characteristic for stem cells. Consequently, the influence of HMGA1 on melanoma maintenance was investigated. In addition to decreased proliferation and reduced anoikis resistance, HMGA1 knockdown reduced melanoma cell survival. Interestingly, the FOSL1 induced pro-tumorigenic effects were demonstrated to be dependent on the HMGA1 level. HMGA1 manipulation reversed FOSL1 induced proliferation and colony forming ability, as well as the anchorage independent growth effect. In conclusion, I could show that additional FOSL1 confers a clear growth benefit to melanoma cells. This benefit is attributed to the induction of stem cell determinants, but can be blocked by the inhibition of the ERK1/2 or PI3K signaling pathways.}, subject = {Melanom}, language = {en} } @phdthesis{Erle2016, author = {Erle, Thorsten Michael}, title = {A Grounded Approach to Psychological Perspective-Taking}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143247}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {„Perspektiven{\"u}bernahme" bezeichnet die F{\"a}higkeit des Menschen, sich in die Lage eines anderen hineinzuversetzen. In der psychologischen Forschung unterscheidet man drei Arten der Perspektiven{\"u}bernahme, n{\"a}mlich perzeptuelle (visuo-spatiale), affektive (Empathie) und kognitive (Theory of Mind). Die letztgenannten Arten der Perspektiven{\"u}bernahme werden oft als „psychologische Perspektiven{\"u}bernahme" zusammengefasst. Diese Dissertation befasst sich mit der Frage, ob diese verschiedenen Arten der Perspektiven{\"u}bernahme als theoretisch unterscheidbare Konstrukte oder lediglich als Facetten ein und desselben Konstrukts angesehen werden sollten. Die Befundlage in der psychologischen Fachliteratur ist diesbez{\"u}glich nicht eindeutig. W{\"a}hrend einige Autoren Korrelationen zwischen verschiedenen Arten der Perspektiven{\"u}bernahme f{\"u}r zu gering erachten, um ein einheitliches Konstrukt zu konstatieren, bewerten andere Autoren Korrelationen derselben Gr{\"o}ße als Evidenz hierf{\"u}r. Ein weniger arbitr{\"a}res Vorgehen w{\"a}re es, experimentalpsychologisch zugrunde liegende Mechanismen zu identifizieren, die allen Arten der Perspektiven{\"u}bernahme gemein sind, und zu untersuchen, ob eine Manipulation dieser Mechanismen abh{\"a}ngige Maße affektiver, kognitiver und perzeptueller Perspektiven{\"u}bernahme gleichermaßen beeinflusst. Diesem Ansatz folgend macht die vorliegende Arbeit die Annahme, dass die mentale Selbstrotation des K{\"o}rperschemas in die Position einer anderen Person, der zentrale Mechanismus visuo-spatialer Perspektiven{\"u}bernahme, ein gemeinsamer Mechanismus aller Arten der Perspektiven{\"u}bernahme ist. Entgegen fr{\"u}herer Ans{\"a}tze wird diese Einheit somit nicht nur {\"u}ber die zentrale gemeinsame Funktionalit{\"a}t aller Arten von Perspektiven{\"u}bernahme, also dem Verlassen des egozentrischen Referenzrahmens zugunsten einer (visuellen, affektiven oder kognitiven) Fremdperspektive, gerechtfertigt, sondern mit der Annahme eines gemeinsamen zugrundeliegenden Mechanismus. Daraus wird die einfache Hypothese abgeleitet, dass visuo-spatiale Perspektiven{\"u}bernahme zu psychologischen Konsequenzen f{\"u}hren kann. Dies wurde in 6 Experimenten getestet. In diesen Experimenten mussten die Probanden zun{\"a}chst immer die visuelle Perspektive einer anderen Person einnehmen. Hierzu sahen die Probanden eine Person, die mit zwei Objekten an einem Tisch sitzt. In jedem Durchgang mussten die Probanden sich entscheiden, mit welcher Hand diese Person eines der beiden Objekte greifen w{\"u}rde. Dabei wurde die Position der Zielperson so manipuliert, dass sie in der H{\"a}lfte der F{\"a}lle im selben visuo-spatialen Referenzrahmen wie der Proband saß, was Perspektiven{\"u}bernahme zur L{\"o}sung der Aufgabe obsolet machte, w{\"a}hrend sie sich in den verbleibenden Durchg{\"a}ngen in einem anderen visuo-spatialen Referenzrahmen befand, so dass die Probanden die visuelle Perspektive der Zielperson {\"u}bernehmen mussten um die Aufgabe korrekt zu l{\"o}sen. Nach jedem Durchgang wurde dem Ziel dieser visuo-spatialen Aufgabe eine psychologische Eigenschaft zugeschrieben. Dies geschah im Rahmen eines abgewandelten Paradigmas zur Untersuchung der Ankerheuristik. Hierzu wurde den Probanden nach jedem Durchgang der visuo-spatialen Aufgabe eine Sch{\"a}tzfrage gestellt. Zeitgleich wurde die Antwort des Ziels bekannt gegeben. Entsprechend der Haupthypothese, dass visuo-spatiale Perspektiven{\"u}bernahme psychologische Konsequenzen erzeugen kann, konnte gezeigt werden, dass die Probanden nach visuo-spatialer Perspektiven{\"u}bernahme in h{\"o}herem Maße die Gedanken der Zielperson {\"u}bernahmen. Dies konnte sowohl anhand der absoluten Gr{\"o}ße des Ankereffekts, als auch anhand der Differenz zwischen den Urteilen der Probanden und der Zielperson, gezeigt werden. Weitere Experimente schlossen Stichprobeneigenschaften, die verwendeten Stimuli oder die Aufgabenschwierigkeit als Alternativerkl{\"a}rungen f{\"u}r diese Effekte aus. Die beiden letzten Experimente zeigten zudem, dass dieser Effekt spezifisch f{\"u}r alle Konstellationen ist, in denen eine mentale Selbstrotation in die Zielperspektive notwendig war und dass die {\"U}bernahme fremder Gedanken mit einem Gef{\"u}hl von {\"A}hnlichkeit assoziiert war. Zusammengenommen unterst{\"u}tzen die Ergebnisse dieser Arbeit die theoretisch abgeleitete Sicht eines einheitlichen Perspektiven{\"u}bernahme-Konstrukts und grenzen dieses zus{\"a}tzlich von verwandten Konstrukten ab. In der abschließenden Diskussion werden die Bedeutung dieser Befunde f{\"u}r die Forschung in den Bereichen Empathie, Theory of Mind, und Perspektiven{\"u}bernahme und ebenfalls praktische Implikationen der Ergebnisse aufgezeigt.}, subject = {Perspektiven{\"u}bernahme}, language = {en} } @phdthesis{Backhaus2016, author = {Backhaus, Philipp}, title = {Effects of Transgenic Expression of Botulinum Toxins in Drosophila}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143279}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Clostridial neurotoxins (botulinum toxins and tetanus toxin) disrupt neurotransmitter release by cleaving neuronal SNARE proteins. We generated transgenic flies allowing for conditional expression of different botulinum toxins and evaluated their potential as tools for the analysis of synaptic and neuronal network function in Drosophila melanogaster by applying biochemical assays and behavioral analysis. On the biochemical level, cleavage assays in cultured Drosophila S2 cells were performed and the cleavage efficiency was assessed via western blot analysis. We found that each botulinum toxin cleaves its Drosophila SNARE substrate but with variable efficiency. To investigate the cleavage efficiency in vivo, we examined lethality, larval peristaltic movements and vision dependent motion behavior of adult Drosophila after tissue-specific conditional botulinum toxin expression. Our results show that botulinum toxin type B and botulinum toxin type C represent effective alternatives to established transgenic effectors, i.e. tetanus toxin, interfering with neuronal and non-neuronal cell function in Drosophila and constitute valuable tools for the analysis of synaptic and network function.}, subject = {Botulinustoxin}, language = {en} } @phdthesis{Rodrigues2016, author = {Rodrigues, Johannes}, title = {Let me change your mind… Frontal brain activity in a virtual T-maze}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143280}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Frontal asymmetry, a construct invented by Richard Davidson, linking positive and negative valence as well as approach and withdrawal motivation to lateralized frontal brain activation has been investigated for over thirty years. The frontal activation patterns described as relevant were measured via alpha-band frequency activity (8-13 Hz) as a measurement of deactivation in electroencephalography (EEG) for homologous electrode pairs, especially for the electrode position F4/ F3 to account for the frontal relative lateralized brain activation. Three different theories about frontal activation patterns linked to motivational states were investigated in two studies. The valence theory of Davidson (1984; 1998a; 1998b) and its extension to the motivational direction theory by Harmon-Jones and Allen (1998) refers to the approach motivation with relative left frontal brain activity (indicated by relative right frontal alpha activity) and to withdrawal motivation with relative right frontal brain activation (indicated by relative left frontal alpha activity). The second theory proposed by Hewig and colleagues (2004; 2005; 2006) integrates the findings of Davidson and Harmon - Jones and Allen with the reinforcement sensitivity theory of Jeffrey A. Gray (1982, 1991). Hewig sees the lateralized frontal approach system and withdrawal system proposed by Davidson as subsystems of the behavioral activation system proposed by Gray and bilateral frontal activation as a biological marker for the behavioral activation system. The third theory investigated in the present studies is the theory from Wacker and colleagues (2003; 2008; 2010) where the frontal asymmetrical brain activation patterns are linked to the revised reinforcement sensitivity theory of Gray and McNaughton (2000). Here, right frontal brain activity (indicated by lower relative right frontal alpha activity) accounts for conflict, behavioral inhibition and activity of the revised behavioral inhibition system, while left frontal brain activation (indicated by lower relative left frontal alpha activity) stands for active behavior and the activity of the revised behavioral activation system as well as the activation of the revised flight fight freezing system. In order to investigate these three theories, a virtual reality T-maze paradigm was introduced to evoke motivational states in the participants, offering the opportunity to measure frontal brain activation patterns via EEG and behavior simultaneously in the first study. In the second study the virtual reality paradigm was additionally compared to mental imagery and a movie paradigm, two well-known state inducing paradigms in the research field of frontal asymmetry. In the two studies, there was confirming evidence for the theory of Hewig and colleages (2004; 2005; 2006), showing higher bilateral frontal activation for active behavior and lateralized frontal activation patterns for approach (left frontal brain activation) and avoidance (right frontal brain activation) behavior. Additionally a limitation for the capability model of anterior brain asymmetry proposed by Coan and colleagues (2006), where the frontal asymmetry should be dependent on the relevant traits driving the frontal asymmetry pattern if a relevant situation occurs, could be found. As the very intense virtual reality paradigm did not lead to a difference of frontal brain activation patterns compared to the mental imagery paradigm or the movie paradigm for the traits of the participants, the trait dependency of the frontal asymmetry in a relevant situation might not be given, if the intensity of the situation exceeds a certain level. Nevertheless there was an influence of the traits in the virtual reality T-maze paradigm, because the shown behavior in the maze was trait-dependent. The implications of the findings are multifarious, leading from possible objective personality testing via diversification of the virtual reality paradigm to even clinical implications for depression treatments based on changes in the lateralized frontal brain activation patterns for changes in the motivational aspects, but also for changes in bilateral frontal brain activation when it comes to the drive and preparedness for action in patients. Finally, with the limitation of the capability model, additional variance in the different findings about frontal asymmetry can be explained by taking the intensity of a state manipulation into account.}, subject = {Electroencephalographie}, language = {en} } @phdthesis{Pieczykolan2016, author = {Pieczykolan, Aleksandra}, title = {Cross-Modal Action Control}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142356}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Multitasking als allgegenw{\"a}rtiges Ph{\"a}nomen wird heutzutage in verschiedenen wissenschaftlichen Disziplinen diskutiert. In der vorliegenden Arbeit wird Multitasking aus der Perspektive der kognitiven Verhaltenswissenschaften beleuchtet mit dem Fokus auf der Rolle von Konfliktl{\"o}sungs- prozessen bei der Verarbeitung von Mehrfacht{\"a}tigkeiten. Insbesondere liegt der Fokus auf kognitiven Mechanismen der crossmodalen Handlungskontrolle, d.h. der Kontrolle von zwei Handlungen in verschiedenen Effektorsystemen. Mit dem Ziel, den bisherigen Umfang derjenigen Handlungsmodalit{\"a}ten zu erweitern, die {\"u}blicherweise in Studien eingesetzt wurden, wurden okulomotorische Reaktionen (d.h. Sakkaden), die bisher als Handlungsmodalit{\"a}t in der Forschung vernachl{\"a}ssigt wurden, in Kombination mit Reaktionen in anderen Efffektorsystemen untersucht (d.h. mit manuellen und vokalen Reaktionen). Weiterhin wurde beabsichtigt, Mechanismen von Crosstalk zu spezifizieren, welches ein Erkl{\"a}rungskonzept darstellt, das sich auf den Aufgabeninhalt bezieht. Crosstalk erscheint besonders relevant f{\"u}r crossmodale Handlungen, da sich Handlungsmodalit{\"a}ten vor allem bez{\"u}glich ihrer Reaktionsmerkmale unterscheiden. In der vorliegenden Arbeit werden vier Studien berichtet, die auf jeweils zwei oder drei Experimenten beruhen. In Studie A wurden crossmodale Doppelreaktionen auf einen einzelnen Stimulus untersucht mit der Fragestellung, wie sich das Zusammenspiel des Vorhandenseins von Reaktionsalternativen und der Kompatibilit{\"a}t zwischen Reaktionen (also dem Crosstalkpotential) auswirkt. In drei Experimenten zeigte sich, dass Crosstalk in mehrere Komponenten dissoziiert werden kann, n{\"a}mlich eine Komponente, die auf der aktuellen Konfliktst{\"a}rke (Online-Crosstalk) basiert, und eine ged{\"a}chtnisbasierte Komponente, die entweder durch Restaktivit{\"a}t vergangener Handlungsanforderungen bestimmt wird (retrospektiver Crosstalk), oder durch Vorbereitung auf zuk{\"u}nftige Handlungsanforderungen (prospektiver Crosstalk). Studie B lieferte Evidenz daf{\"u}r, dass okulomotorische Reaktionen sowohl struktureller als auch inhaltsbasierte Interferenz unterliegen. In drei Experimenten wurde das Paradigma zeitlich {\"u}berlappender Aufgaben verwendet, bei dem zwei Stimuli mit zeitlichem Versatz pr{\"a}sentiert wurden, auf die jeweils mit einer okulomotorischen und einer manuellen Handlung reagiert werden musste. Dabei wurden sowohl Hinweise auf einen seriellen als auch auf einen parallelen Verarbeitungsmodus gefunden. Weiterhin deuteten die Ergebnisse darauf hin, dass abh{\"a}ngig von der Aufgabenkompatibilit{\"a}t zwischen diesen Verarbeitungsmodi gewechselt wurde, d.h. zu eher paralleler Verarbeitung bei kompatiblen Aufgabenanforderungen und zu eher serieller Verarbeitung bei inkompatiblen Aufgabenanforderungen. In Studie C wurden Verarbeitungspriorit{\"a}ten zwischen Effektorsystemen untersucht. In zwei Experimenten zeigte sich, dass das zuvor berichtete Verarbeitungsdominanzmuster repliziert werden konnte, bei der okulomotorische Reaktionen vokale Reaktionen dominieren und diese wiederum manuelle Reaktionen dominieren. Die relative St{\"a}rke der Dominanz konnte allerdings bei vorhandenem Reaktionskonflikt angepasst werden. Die Verarbeitungspriorit{\"a}ten wurden hierbei zum Teil in Richtung derjenigen Reaktion verschoben, in der bereits ein Konflikt im Bezug auf die Kompatibilit{\"a}t zwischen Stimulus und Reaktion gel{\"o}st werden musste. Dieses Ergebnis zeigt, dass Verarbeitungspriorit{\"a}ten flexibel an die spezifischen Handlungsanforderungen angepasst werden k{\"o}nnen. Studie D besch{\"a}ftigte sich mit einem bisher weitgehend vernachl{\"a}ssigten Bereich innerhalb der Doppelaufgabenforschung, n{\"a}mlich der Kontrolle der zeitlichen Reaktionsreihenfolge. In einer drei Experimente umfassenden Untersuchung wurden mehrere Faktoren variiert, die sich in fr{\"u}heren Studien bereits als relevant f{\"u}r Mechanismen der Doppelaufgabeninterferenz gezeigt haben. In der vorliegenden Studie wurde gezeigt, dass die finale Reaktionsreihenfolge in einem Handlungsdurchgang das Ergebnis eines kontinuierlichen Anpassungsprozesses ist, welcher auf dem Zusammenspiel mehrerer top-down-Faktoren, z.B. der Antizipation von Reaktionsmerkmalen, und mehrerer bottom-up-Faktoren, wie z.B. der Stimulusreihenfolge oder der Aufgabenkompatibilit{\"a}t, basiert. Die vorliegende Arbeit liefert somit einen wichtigen Beitrag zum Fortschritt des Verst{\"a}ndnisses der Verarbeitung komplexer Handlungsanforderungen aus der Perspektive crossmodaler Handlungen. Insbesondere wurden Spezifikationen f{\"u}r Mechanismen der Effektorpriorisierung und der Kontrolle der Reaktionsreihenfolge als auch eine neuartige Taxonomie von Crosstalk vorgestellt, welche als umfassende Rahmenvorstellung zur Erkl{\"a}rung von Interferenzmechanismen bei Kontrollprozessen von Mehrfachanforderungen dienlich sein kann.}, subject = {Kognition}, language = {en} } @phdthesis{Schweinlin2016, author = {Schweinlin, Matthias Oliver}, title = {Development of advanced human intestinal in vitro models}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142571}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {The main function of the small intestine is the absorption of essential nutrients, water and vitamins. Moreover, it constitutes a barrier protecting us from toxic xenobiotics and pathogens. For a better understanding of these processes, the development of intestinal in vitro models is of great interest to the study of pharmacological and pathological issues such as transport mechanisms and barrier function. Depending on the scientific questions, models of different complexity can be applied. In vitro Transwell® systems based on a porous PET-membrane enable the standardized study of transport mechanisms across the intestinal barrier as well as the investigation of the influence of target substances on barrier integrity. However, this artificial setup reflects only limited aspects of the physiology of the native small intestine and can pose an additional physical barrier. Hence, the applications of this model for tissue engineering are limited. Previously, tissue models based on a biological decellularized scaffold derived from porcine gut tissue were demonstrated to be a good alternative to the commonly used Transwell® system. This study showed that preserved biological extracellular matrix components like collagen and elastin provide a natural environment for the epithelial cells, promoting cell adhesion and growth. Intestinal epithelial cells such as Caco-2 cultured on such a scaffold showed a confluent, tight monolayer on the apical surface. Additionally, myofibroblasts were able to migrate into the scaffold supporting intestinal barrier formation. In this thesis, dendritic cells were additionally introduced to this model mimicking an important component of the immune system. This co-culture model was then successfully proven to be suitable for the screening of particle formulations developed as delivery system for cancer antigens in peroral vaccination studies. In particular, nanoparticles based on PLGA, PEG-PAGE-PLGA, Mannose-PEG-PAGE-PLGA and Chitosan were tested. Uptake studies revealed only slight differences in the transcellular transport rate among the different particles. Dendritic cells were shown to phagocytose the particles after they have passed the intestinal barrier. The particles demonstrated to be an effective carrier system to transport peptides across the intestinal barrier and therefore present a useful tool for the development of novel drugs. Furthermore, to mimic the complex structure and physiology of the gut including the presence of multiple different cell types, the Caco-2 cell line was replaced by primary intestinal cells to set up a de novo tissue model. To that end, intestinal crypts including undifferentiated stem cells and progenitor cells were isolated from human small intestinal tissue samples (jejunum) and expanded in vitro in organoid cultures. Cells were cultured on the decellularized porcine gut matrix in co-culture with intestinal myofibroblasts. These novel tissue models were maintained under either static or dynamic conditions. Primary intestinal epithelial cells formed a confluent monolayer including the major differentiated cell types positive for mucin (goblet cells), villin (enterocytes), chromogranin A (enteroendocrine cells) and lysozyme (paneth cells). Electron microscopy images depicted essential functional units of an intact epithelium, such as microvilli and tight junctions. FITC-dextran permeability and TEER measurements were used to assess tightness of the cell layer. Models showed characteristic transport activity for several reference substances. Mechanical stimulation of the cells by a dynamic culture system had a great impact on barrier integrity and transporter activity resulting in a tighter barrier and a higher efflux transporter activity. In Summary, the use of primary human intestinal cells combined with a biological decellularized scaffold offers a new and promising way to setup more physiological intestinal in vitro models. Maintenance of primary intestinal stem cells with their proliferation and differentiation potential together with adjusted culture protocols might help further improve the models. In particular, dynamic culture systems and co culture models proofed to be a first crucial steps towards a more physiological model. Such tissue models might be useful to improve the predictive power of in vitro models and in vitro in vivo correlation (IVIVC) studies. Moreover, these tissue models will be useful tools in preclinical studies to test pharmaceutical substances, probiotic active organisms, human pathogenic germs and could even be used to build up patient-specific tissue model for personalized medicine.}, subject = {Tissue Engineering}, language = {en} } @phdthesis{Karl2016, author = {Karl, Stefan}, title = {Control Centrality in Non-Linear Biological Networks}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150838}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Biological systems such as cells or whole organisms are governed by complex regulatory networks of transcription factors, hormones and other regulators which determine the behavior of the system depending on internal and external stimuli. In mathematical models of these networks, genes are represented by interacting "nodes" whose "value" represents the activity of the gene. Control processes in these regulatory networks are challenging to elucidate and quantify. Previous control centrality metrics, which aim to mathematically capture the ability of individual nodes to control biological systems, have been found to suffer from problems regarding biological plausibility. This thesis presents a new approach to control centrality in biological networks. Three types of network control are distinguished: Total control centrality quantifies the impact of gene mutations and identifies potential pharmacological targets such as genes involved in oncogenesis (e.g. zinc finger protein GLI2 or bone morphogenetic proteins in chondrocytes). Dynamic control centrality describes relaying functions as observed in signaling cascades (e.g control in mouse colon stem cells). Value control centrality measures the direct influence of the value of the node on the network (e.g. Indian hedgehog as an essential regulator of proliferation in chondrocytes). Well-defined network manipulations define all three centralities not only for nodes, but also for the interactions between them, enabling detailed insights into network pathways. The calculation of the new metrics is made possible by substantial computational improvements in the simulation algorithms for several widely used mathematical modeling paradigms for genetic regulatory networks, which are implemented in the regulatory network simulation framework Jimena created for this thesis. Applying the new metrics to biological networks and artificial random networks shows how these mathematical concepts correspond to experimentally verified gene functions and signaling pathways in immunity and cell differentiation. In contrast to controversial previous results even from the Barab{\´a}si group, all results indicate that the ability to control biological networks resides in only few driver nodes characterized by a high number of connections to the rest of the network. Autoregulatory loops strongly increase the controllability of the network, i.e. its ability to control itself, and biological networks are characterized by high controllability in conjunction with high robustness against mutations, a combination that can be achieved best in sparsely connected networks with densities (i.e. connections to nodes ratios) around 2.0 - 3.0. The new concepts are thus considerably narrowing the gap between network science and biology and can be used in various areas such as system modeling, plausibility trials and system analyses. Medical applications discussed in this thesis include the search for oncogenes and pharmacological targets, as well their functional characterization.}, subject = {Bioinformatik}, language = {en} } @phdthesis{Muenchow2016, author = {M{\"u}nchow, Hannes}, title = {I feel, therefore I learn - Effectiveness of affect induction interventions and possible covariates on learning outcomes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148432}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {Affective states in the context of learning and achievement can influence the learning process essentially. The impact of affective states can be both directly on the learning performance and indirectly mediated via, for example, motivational processes. Positive activating affect is often associated with increased memory skills as well as advantages in creative problem solving. Negative activating affect on the other hand is regarded to impair learning outcomes because of promoting task-irrelevant thinking. While these relationships were found to be relatively stable in correlation studies, causal relationships have been examined rarely so far. This dissertation aims to investigate the effects of positive and negative affective states in multimedia learning settings and to identify potential moderating factors. Therefore, three experimental empirical studies on university students were conducted. In Experiment 1, N = 57 university students were randomly allocated to either a positive or negative affect induction group. Affects were elicited using short film clips. After a 20-minute learning phase in a hypertext-based multimedia learning environment on "functional neuroanatomy" the learners' knowledge as well as transfer performance were measured. It was assumed that inducing positive activating affect should enhance learning performance. Eliciting negative activating affect on the other hand should impair learning performance. However, it was found that the induction of negative activating affect prior to the learning phase resulted in slight deteriorations in knowledge. Contrary to the assumptions, inducing positive activating affect before the learning phase did not improve learning performance. Experiment 2 induced positive activating affect directly during learning. To induce affective states during the entire duration of the learning phase, Experiment 2 used an emotional design paradigm. Therefore, N = 111 university students were randomly assigned to learn either in an affect inducing multimedia learning environment (use of warm colours and round shapes) or an affectively neutral counterpart (using shades of grey and angular shapes) on the same topic as in Experiment 1. Again, knowledge as well as transfer performance were measured after learning for 20 minutes. In addition, positive and negative affective states were measured before and after learning. Complex interaction patterns between the treatment and initial affective states were found. Specifically, learners with high levels of positive affect before learning showed better transfer performance when they learned in the affect inducing learning environment. Regarding knowledge, those participants who reported high levels of negative activating affect prior to the learning period performed worse. However, the effect on knowledge did not occur for those students learning in the affect inducing learning environment. For knowledge, the treatment therefore protected against poorer performance due to high levels of negative affective states. Results of Experiment 2 showed that the induction of positive activating affect influenced learning performance positively when taking into account affective states prior to the learning phase. In order to confirm these interaction effects, a conceptual replication of the previous experiment was conducted in Experiment 3. Experiment 3 largely retained the former study design, but changed the learning materials and tests used. Analogous to Experiment 2, N = 145 university students learning for 20 minutes in either an affect inducing or an affectively neutral multimedia learning environment on "eukaryotic cell". To strengthen the treatment, Experiment 3 also used anthropomorphic design elements to induce affective states next to warm colours and round shapes. Moreover, in order to assess the change in affective states more exactly, an additional measurement of positive and negative affective states after half of the learning time was inserted. Knowledge and transfer were assessed again to measure learning performance. The learners' memory skills were used as an additional learning outcome. To control the influence of potential confounding variables, the participants' general and current achievement motivation as well as interest, and emotion regulation skills were measured. Contrary to the assumptions, Experiment 3 could not confirm the interaction effects of Experiment 2. Instead, there was a significant impact of positive activating affect prior to the learning phase on transfer, irrespective of the learners' group affiliation. This effect was further independent of the control variables that were measured. Nevertheless, the results of Experiment 3 fit into the picture of findings regarding "emotional design" in hypermedia learning settings. To date, the few publications that have used this approach propose heterogeneous results, even when using identical materials and procedures.}, subject = {Affekt}, language = {en} } @article{ZhuShabalaCuinetal.2016, author = {Zhu, Min and Shabala, Lana and Cuin, Tracey A and Huang, Xin and Zhou, Meixue and Munns, Rana and Shabala, Sergey}, title = {Nax loci affect SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger expression and activity in wheat}, series = {Journal of Experimental Botany}, volume = {67}, journal = {Journal of Experimental Botany}, number = {3}, doi = {10.1093/jxb/erv493}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150236}, pages = {835-844}, year = {2016}, abstract = {Salinity stress tolerance in durum wheat is strongly associated with a plant's ability to control Na\(^{+}\) delivery to the shoot. Two loci, termed Nax1 and Nax2, were recently identified as being critical for this process and the sodium transporters HKT1;4 and HKT1;5 were identified as the respective candidate genes. These transporters retrieve Na\(^{+}\) from the xylem, thus limiting the rates of Na\(^{+}\) transport from the root to the shoot. In this work, we show that the Nax loci also affect activity and expression levels of the SOS1-like Na\(^{+}\)/H\(^{+}\) exchanger in both root cortical and stelar tissues. Net Na\(^{+}\) efflux measured in isolated steles from salt-treated plants, using the non-invasive ion flux measuring MIFE technique, decreased in the sequence: Tamaroi (parental line)>Nax1=Nax2>Nax1:Nax2 lines. This efflux was sensitive to amiloride (a known inhibitor of the Na\(^{+}\)/H\(^{+}\) exchanger) and was mirrored by net H\(^{+}\) flux changes. TdSOS1 relative transcript levels were 6-10-fold lower in Nax lines compared with Tamaroi. Thus, it appears that Nax loci confer two highly complementary mechanisms, both of which contribute towards reducing the xylem Na\(^{+}\) content. One enhances the retrieval of Na\(^{+}\) back into the root stele via HKT1;4 or HKT1;5, whilst the other reduces the rate of Na\(^{+}\) loading into the xylem via SOS1. It is suggested that such duality plays an important adaptive role with greater versatility for responding to a changing environment and controlling Na\(^{+}\) delivery to the shoot.}, language = {en} } @article{NeuderthSchwarzGerlichetal.2016, author = {Neuderth, Silke and Schwarz, Betje and Gerlich, Christian and Schuler, Michael and Markus, Miriam and Bethge, Matthias}, title = {Work-related medical rehabilitation in patients with musculoskeletal disorders: the protocol of a propensity score matched effectiveness study (EVA-WMR, DRKS00009780)}, series = {BMC Public Health}, volume = {16}, journal = {BMC Public Health}, number = {804}, doi = {10.1186/s12889-016-3437-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150015}, year = {2016}, abstract = {Background Musculoskeletal disorders are one of the most important causes of work disability. Various rehabilitation services and return-to-work programs have been developed in order to reduce sickness absence and increase sustainable return-to-work. As the effects of conventional medical rehabilitation programs on sickness absence duration were shown to be slight, work-related medical rehabilitation programs have been developed and tested. While such studies proved the efficacy of work-related medical rehabilitation compared with conventional medical rehabilitation in well-conducted randomized controlled trials, its effectiveness under real-life conditions has yet to be proved. Methods/Design The cohort study will be performed under real-life conditions with two parallel groups. Participants will receive either a conventional or a work-related medical rehabilitation program. Propensity score matching will be used to identify controls that are comparable to treated work-related medical rehabilitation patients. Over a period of three months, about 18,000 insured patients with permission to undergo a musculoskeletal rehabilitation program will be contacted. Of these, 15,000 will receive a conventional and 3,000 a work-related medical rehabilitation. We expect a participation rate of 40 \% at baseline. Patients will be aged 18 to 65 years and have chronic musculoskeletal disorders, usually back pain. The control group will receive a conventional medical rehabilitation program without any explicit focus on work, work ability and return to work in diagnostics and therapy. The intervention group will receive a work-related medical rehabilitation program that in addition to common rehabilitation treatments contains 11 to 25 h of work-related treatment modules. Follow-up data will be assessed three and ten months after patients' discharge from the rehabilitation center. Additionally, department characteristics will be assessed and administrative data records used. The primary outcomes are sick leave duration, stable return to work and subjective work ability. Secondary outcomes cover several dimensions of health, functioning and coping strategies. Discussion This study will determine the relative effectiveness of a complex, newly implemented work-related rehabilitation strategy for patients with musculoskeletal disorders.}, language = {en} } @phdthesis{Pfeuffer2016, author = {Pfeuffer, Rebekka Christina}, title = {Growth and characterization of II-VI semiconductor nanowires grown by Au catalyst assisted molecular beam epitaxy}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141385}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {In the present PhD thesis the control of the morphology, such as the diameter, the length, the orientation, the density, and the crystalline quality of 1D ZnSe NWs grown by MBE for optical and transport applications has been achieved.}, subject = {Zinkselenid}, language = {en} } @phdthesis{Hennighausen2016, author = {Hennighausen, Anna Christine}, title = {Costly signaling with mobile devices: An evolutionary psychological perspective on smartphones}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141049}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2016}, abstract = {In the last decade, mobile device ownership has largely increased. In particular, smartphone ownership is constantly rising (A. Smith, 2015; Statista, 2016a), and there is a real hype for luxury brand smartphones (Griffin, 2015). These observations raise the question of which functions smartphones serve in addition to their original purposes of making and receiving calls, searching for information, and organizing. Beyond these obvious functions, studies suggest that smartphones express fashion, lifestyle, and one's economic status (e.g., B{\o}dker et al., 2009; Statista, 2016b; Vanden Abeele, Antheunis, \& Schouten, 2014). Specifically, individuals seem to purchase and use conspicuous luxury brand smartphones to display and enhance status (D. Kim et al., 2014; M{\"u}ller-Lietzkow et al., 2014; Suki, 2013). But how does owning a conspicuous, high-status smartphone contribute to status, and which benefits may these status boosts provide to their owners? From an evolutionary perspective, status carries a lot of advantages, particularly for males; high status grants them priority access to resources and correlates with their mating success (van Vugt \& Tybur, 2016). In this sense, research suggests that men conspicuously display their cell phones to attract mates and to distinguish themselves from rivals (Lycett \& Dunbar, 2000). In a similar vein, evolutionarily informed studies on conspicuous consumption indicate that the purchase and display of conspicuous luxuries (including mobile phones and smartphones) relate to a man's interest in uncommitted sexual relationships and enhance his desirability as a short-term mate (Hennighausen \& Schwab, 2014; Saad, 2013; Sundie et al., 2011). Drawing on these findings, this doctoral dissertation investigated how a man is perceived given that he is an owner of a high-status (vs. nonconspicuous, low-status) smartphone as a romantic partner and male rival. This was done in three experiments. In addition, it was examined how male conspicuous consumption of smartphones interacted with further traits that signal a man's mate quality, namely facial attractiveness (Studies 1 and 2) and social dominance (Study 3). Study 1 revealed that men and women perceived a male owner of a conspicuous smartphone as a less desirable long-term mate and as more inclined toward short-term mating. Study 2 replicated these results and showed that men and women assigned traits that are associated with short-term mating (e.g., low loyalty, interest in flirts, availability of tangible resources) to a male owner of a conspicuous smartphone and perceived him as a stronger male rival and mate poacher, and less as a friend. The results of Study 2 further suggested that specifically more attractive men might benefit from owning a conspicuous smartphone in a short-term mating context and might be hence considered as stronger male rivals. Study 3 partially replicated the findings of Studies 1 and 2 pertaining to the effects of owning a conspicuous smartphone. Study 3 did not show different effects of conspicuous consumption of smartphones on perceptions of a man dependent on the level of his social dominance. To conclude, the findings of this doctoral dissertation suggest that owning a conspicuous, high-status smartphone might not only serve proximate functions (e.g., making and receiving calls, organization) but also ultimate functions, which relate to mating and reproduction. The results indicate that owning a conspicuous smartphone might yield benefits for men in a short-term rather than in a long-term mating context. Furthermore, more attractive men appear to benefit more from owning a conspicuous smartphone than less attractive men. These findings provide further insights into the motivations that underlie men's purchases and displays of conspicuous, high-status smartphones from luxury brands that reach beyond the proximate causes frequently described in media and consumer psychological research. By applying an evolutionary perspective, this doctoral dissertation demonstrates the power and utility of this research paradigm for media psychological research and shows how combining a proximate and ultimate perspective adds to a more profound understanding of smartphone phenomena.}, subject = {Verbraucher}, language = {en} }