@phdthesis{Wetzel2013,
  author    = {Wetzel, Andrea},
  title     = {The role of TrkB and NaV1.9 in activity-dependent axon growth in motoneurons},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-92877},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {W{\"a}hrend der Entwicklung des Nervensystems lassen sich bei Motoneuronen aktivit{\"a}tsabh{\"a}ngige Kalziumstr{\"o}me eobachten, die das Axonwachstum regulieren. Diese Form der neuronalen Spontanaktivit{\"a}t sowie das Auswachsen von Axonen sind bei Motoneuronen, die aus Tiermodellen der Spinalen Muskelatrophie isoliert werden, gest{\"o}rt. Experimente aus unserer Arbeitsgruppe haben gezeigt, dass spontane Erregbarkeit und aktivit{\"a}tsabh{\"a}ngiges Axonwachstum von kultivierten Motoneuronen auch unter Verwendung von Toxinen beeintr{\"a}chtigt sind, welche die Aktivit{\"a}t von spannungsabh{\"a}ngigen Natriumkan{\"a}len blockieren. In diesen Versuchen war die Wirkung von Saxitoxin effizienter als die Wirkung von Tetrodotoxin. Wir identifizierten den Saxitoxin-sensitiven/Tetrodotoxin-insensitiven spannungsabh{\"a}ngigen Natriumkanal NaV1.9 als Trigger f{\"u}r das {\"O}ffnen spannungsabh{\"a}ngiger Kalziumkan{\"a}le. Die Expression von NaV1.9 in Motoneuronen konnte {\"u}ber quantitative RT-PCR nachgewiesen werden und antik{\"o}rperf{\"a}rbungen offenbarten eine Anreicherung des Kanals im axonalen Wachstumskegel sowie an Ranvier'schen Schn{\"u}rringen von isolierten Nervenfasern wildtypischer M{\"a}use. Motoneurone von NaV1.9 knock-out M{\"a}usen zeigen reduzierte Spontanaktivit{\"a}t und eine Reduktion des Axonwachstums, welche durch NaV1.9 {\"U}berexpression normalisiert werden kann. In Motoneuronen von Smn-defizienten M{\"a}usen konnte keine Abweichung der NaV1.9 Proteinverteilung nachgewiesen werden. K{\"u}rzlich wurden Patienten identifiziert, die eine missense-Mutation im NaV1.9 kodierenden SCN11A Gen tragen. Diese Patienten k{\"o}nnen keinerlei Schmerz empfinden und leiden zudem an Muskelschw{\"a}che in Kombination mit einer verz{\"o}gerten motorischen Entwicklung. Im Rahmen dieser Doktorarbeit konnten molekularbiologische Untersuchungen an M{\"a}usen, welche die Mutation im orthologen Scn11a Gen tragen, zur Aufkl{\"a}rung des Krankheitsmechanismus beitragen. Die Kooperationsstudie zeigte, dass eine gesteigerte Funktion von NaV1.9 diese spezifische Kanalerkrankung ausl{\"o}st, was die Wichtigkeit von NaV1.9 in menschlichen Motoneuronen unterstreicht. Eine fr{\"u}here Studie beschrieb an hippocampalen Neuronen, dass die Rezeptortyrosinkinase tropomyosin receptor kinase B (TrkB) den NaV1.9 Kanal {\"o}ffnen kann. Im Wachstumskegel von Motoneuronen ist TrkB nachweisbar und folglich in r{\"a}umlicher N{\"a}he zu NaV1.9 zu finden. Um zu pr{\"u}fen, ob TrkB in die spontane Erregbarkeit von Motoneuronen involviert ist, wurden TrkB knock-out M{\"a}use untersucht. Isolierte Motoneurone von TrkB knock-out M{\"a}usen weisen eine Reduktion der Spontanaktivit{\"a}t und eine Verringerung des Axonwachstums auf. Ob TrkB und NaV1.9 hierbei funktionell gekoppelt sind, ist Gegenstand k{\"u}nftiger Forschung.},
  subject      = {Motoneuron},
  language  = {en}
}
@article{KoerdtSiebersBlochetal.2013,
  author    = {Koerdt, Steffen and Siebers, Joerg and Bloch, Wilhelm and Ristow, Oliver and Kuebler, Alexander C. and Reuther, Tobias},
  title     = {Immunohistochemial study on the expression of von Willebrand factor (vWF) after onlay autogenous iliac grafts for lateral alveolar ridge augmentation},
  doi       = {10.1186/1746-160X-9-40},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110142},
  year      = {2013},
  abstract  = {Introduction The main problems of autogenous bone transplants are their unpredictable atrophy and their loss of structure. One key factor lies in the poor revascularization of simple onlay grafts. The the aim of this study was to evaluate the revascularization processes in autogenous bone grafts from the iliac crest to the alveolar ridge. Methods In a sheep model, autogenous bone grafts were harvested from the iliac crest. A combination of a resorbable collagen membrane (CM) and deproteinized bovine bone material (DBBM) was used to modify the bone graft (experiment 2). This was compared with a simple onlay bone graft (control group, experiment 1). The amount of vessels in bone and connective tissue (CT), and the amount of CT were analyzed. The expression of von Willebrand factor (vWF) was compared between the two experimental groups using immunohistochemical analysis. Results The ratio of the amount of vessels in bone and CT changed over time, and more vessels could be detected in bone at 12-16 weeks of graft healing. The number of vessels were significantly higher in experiment 2 than in experiment 1. More CT was found in experiment 1, whereas the amount of CT in both experiments decreased over time. Conclusion This study shows a more intensive and extensive revascularization in experiment 2, as significantly more vessels were detected. The decreased amount of CT in experiment 2 clarifies its clinical superiority.},
  language  = {en}
}
@misc{Proell2013,
  type      = {Master Thesis},
  author    = {Pr{\"o}ll, Sebastian},
  title     = {Stability of Switched Epidemiological Models},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108573},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {In this thesis it is shown how the spread of infectious diseases can be described via mathematical models that show the dynamic behavior of epidemics. Ordinary differential equations are used for the modeling process. SIR and SIRS models are distinguished, depending on whether a disease confers immunity to individuals after recovery or not. There are characteristic parameters for each disease like the infection rate or the recovery rate. These parameters indicate how aggressive a disease acts and how long it takes for an individual to recover, respectively. In general the parameters are time-varying and depend on population groups. For this reason, models with multiple subgroups are introduced, and switched systems are used to carry out time-variant parameters. When investigating such models, the so called disease-free equilibrium is of interest, where no infectives appear within the population. The question is whether there are conditions, under which this equilibrium is stable. Necessary mathematical tools for the stability analysis are presented. The theory of ordinary differential equations, including Lyapunov stability theory, is fundamental. Moreover, convex and nonsmooth analysis, positive systems and differential inclusions are introduced. With these tools, sufficient conditions are given for the disease-free equilibrium of SIS, SIR and SIRS systems to be asymptotically stable.},
  subject      = {Gew{\"o}hnliche Differentialgleichung},
  language  = {en}
}
@phdthesis{DasGupta2013,
  author    = {Das Gupta, Mithun},
  title     = {Analyse von MicroRNA-Profilen in humanen dendritischen Zellen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108326},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {The field of microRNA research has gained enormous significance during recent years. Current studies have shown that microRNAs play an important role in many biological processes via posttranscriptional gene regulation. This also applies for the TLR-mediated recognition of pathogens by immune cells. Among others, the microRNAs miR-132, miR-146a and miR-155 have been characterized by various authors. However, the specific role of microRNAs in the defense against fungal infections by Aspergillus fumigatus has not been investigated so far, although this ubiquitous mold causes severe infections in immuno-compromised patients. As dendritic cells play a pivotal part in the in vivo recognition of A. fumigatus, the present study investigates the reaction of these cells to A. fumigatus and other pathogens on the microRNA level. For this purpose, dendritic cells were incubated with different forms of A. fumigatus and other pathogens for up to twelve hours. Subsequently, the expression of miR-132, miR-146a and miR-155 was quantified by real-time PCR. Levels of miR-132 in dendritic cells were significantly increased after stimulation with living germ tubes of A. fum, but showed no change after treatment with LPS. Relative expression level of miR-146a was moderately elevated upon stimulation with LPS, but did not respond to co-cultivation with living germ tubes. MiR-155 was highly induced by both stimuli. These results show, that dependent on the stimulus, microRNAs are differentially regulated in dendritic cells. Among the tested microRNAs, miR-155 showed the strongest and most stable expression values. Therefore, further experiments focused on this mircoRNA. It was shown, that the up-regulation of miR-155 is dependent on the germination stage of the fungus. Induction of miR-155 was low with conidia, moderate with hyphae and high with germ tubes. The extent of miR-155 induction also corresponded with the multiplicity of infection (MOI), with higher MOIs triggering a stronger miR-155 response. These results suggest that miR-132 and miR-155 play an important role in the immunologic reaction of DCs against A. fumigatus and that a further characterization of these microRNA, especially with respect to their specific function in DCs, could contribute to the understanding of the biological mechanisms of Aspergillosis.},
  subject      = {Aspergillus fumigatus},
  language  = {en}
}
@phdthesis{Zancolli2013,
  author    = {Zancolli, Giulia},
  title     = {Amphibian diversity along the slope of Mount Kilimanjaro: from species to genes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-91792},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {1. Since the early nineteenth century describing (and understanding) patterns of distribution of biodiversity across the Earth has represented one of the most significant intellectual challenges to ecologists and biogeographers. Among the most striking patterns of species richness are: the latitudinal and elevational gradients, with peaks in number of species at low latitudes and somewhere at mid altitudes, although other patterns, e.g. declines with increasing elevation, are often observed. Even in highly diverse tropical regions, species richness is not evenly distributed but there are "hotspots" of biodiversity where an exceptional number of species, especially endemics, are concentrated. Unfortunately, such areas are also experiencing dramatic loss of habitat. Among vertebrate taxa, amphibians are facing the most alarming number of extinctions. Habitat destruction, pollution and emergence of infectious diseases such as chytridiomycosis, are causing worldwide population declines. Responses to these drivers can be multidirectional and subtle, i.e. they may not be captured at the species but at the genetic level. Moreover, present patterns of diversity can result from the influence of past geological, climatic and environmental changes. In this study, I used a multidisciplinary and multilevel approach to understand how and to which extent the landscape influences amphibian diversity. Mount Kilimanjaro is an exceptional tropical region where the landscape is rapidly evolving due to land use changes; additionally, there is a broad lack of knowledge of its amphibian fauna. During two rainy seasons in 2011, I recorded anurans from the foothills to 3500 m altitude; in addition, I focused on two river frog species and collected tissue samples for genetic analysis and swabs for detection of chytridiomycosis, the deadly disease caused by Batrachochytrium dendrobatidis (Bd). 2. I analyzed how species richness and composition change with increasing elevation and anthropogenic disturbance. In order to disentangle the observed patterns of species diversity and distribution, I incorporated inferences from historical biogeography and compared the assemblage of Mt. Kilimanjaro and Mt. Meru (both recent volcanoes) with those of the older Eastern Arc Mountains. Species richness decreased with elevation and locally increased in presence of water bodies, but I did not detect effects of either anthropogenic disturbance or vegetation structure on species richness and composition. Moreover, I found a surprisingly low number of forest species. Historical events seem to underlie the current pattern of species distribution; the young age of Mt. Kilimanjaro and the complex biogeographic processes which occurred in East Africa during the last 20 million years prevented montane forest frogs from colonizing the volcano. 3. I focused on the genetic level of biodiversity and investigated how the landscape, i.e. elevation, topographic relief and land cover, influence genetic variation, population structure and gene flow of two ecologically similar and closely related river frog species, namely Amietia angolensis and Amietia wittei. I detected greater genetic differentiation among populations in the highland species (A. wittei) and higher genetic variation in the lowland species (A. angolensis), although genetic diversity was not significantly correlated with elevation. Importantly, human settlements seemed to restrict gene flow in A. angolensis, whereas steep slopes were positively correlated with gene flow in A. wittei. This results show that even ecologically similar species can respond differently to landscape processes and that the spatial configuration of topographic features combined with species-specific biological attributes can affect dispersal and gene flow in disparate ways. 4. River frogs of the genus Amietia seem to be particularly susceptible to chytridiomycosis, showing the highest pathogen load in Kenya and other African countries. In the last study, I collected swab samples from larvae of A. angolensis and A. wittei for Bd detection. Both species resulted Bd-positive. The presence of Bd on Mt. Kilimanjaro has serious implication. For instance, Bd can be transported by footwear of hikers from contaminated water and soil. Tourists visiting Mt. Kilimanjaro may translocate Bd zoospores to other areas such as the nearby Eastern Arc Mts. where endemic and vulnerable species may still be na{\"i}ve to the fungus and thus suffer of population declines. 5. My study significantly contributed to the knowledge of the amphibian fauna of Mt. Kilimanjaro and of East Africa in general, and it represents a valuable tool for future conservation actions and measures. Finally, it highlights the importance of using a multidisciplinary (i.e. community ecology, historical biogeography, landscape genetics, disease ecology) and multilevel (i.e. community, species, population, gene) approach to disentangle patterns of biodiversity.},
  subject      = {Kilimandscharo},
  language  = {en}
}
@phdthesis{Bollmann2013,
  author    = {Bollmann, Stefan},
  title     = {Structural Dynamics of Oligopeptides determined by Fluorescence Quenching of Organic Dyes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-92191},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {For determination of structures and structural dynamics of proteins organic fluorophores are a standard instrument. Intra- and intermolecular contact of biomolecular structures are determined in time-resolved and stationary fluorescence microscopy experiments by quenching of organic fluorophores due to Photoinduced Electron Transfer (PET) and dimerization interactions. Using PET we show in this work that end-to-end contact dynamics of serine-glycine peptides are slowed down by glycosylation. This slow down is due to a change in reaction enthalpy for end-to-end contact and is partly compensated by entropic effects. In a second step we test how dimerization of MR121 fluorophore pairs reports on end-to-end contact dynamics. We show that in aqueous solutions containing strong denaturants MR121 dimerization reports advantageously on contact dynamics for glycine-serine oligopeptides compared to the previously used MR121/tryptophane PET reporters. Then we analyze dimer interactions and quenching properties of different commercially available fluorophores being standards in F{\"o}rster Resonance Energy Transfer (FRET) measurements. Distances in biomolecules are determinable using FRET, but for very flexible biomolecules the analysis of masurement data can be distorted if contact of the two FRET fluorophores is likely. We quantify how strong the quenching of fluorophore pairs with two different or two identical fluorophores is. Dimer spectra and association constants are quantified to estimate if fluophores are applicable in various applications, e.g. in FRET measurements with unstructured peptides and proteins.},
  subject      = {Fluorophore},
  language  = {en}
}
@phdthesis{Dengel2013,
  author    = {Dengel, Radu-Gabriel},
  title     = {Fabrication of magnetic artificial atoms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-103162},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {This thesis presents the detailed development of the fabrication process and the first observations of artificial magnetic atoms from the II-VI diluted magnetic semiconductor alloy (Zn,Cd,Be,Mn)Se. In order to manufacture the vertical quantum dot device which exhibits artificial atom behavior a number of development steps are conducted. First, the II-VI heterostructure is adjusted for the linear transport regime. Second, state of the art vertical quantum dot fabrication techniques in the III-V material system are investigated regarding their portability to the II-VI heterostructure. And third, new approaches to the fabrication process are developed, taking into account the complexity of the heterostructure and its physical properties. Finally a multi-step fabrication process is presented, which is built up from electron beam and optical lithography, dry and wet etching and insulator deposition. This process allows for the processing of pillars with diameters down to 200 nm with an insulating dielectric and gate. Preliminary transport data on the fabricated vertical quantum dots are presendted confirming the magnetic nature of the resulting artificial atoms.},
  subject      = {Zwei-Sechs-Halbleiter},
  language  = {en}
}
@phdthesis{Ljaschenko2013,
  author    = {Ljaschenko, Dmitrij},
  title     = {Hebbian plasticity at neuromuscular synapses of Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-90465},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Synaptic plasticity determines the development of functional neural circuits. It is widely accepted as the mechanism behind learning and memory. Among different forms of synaptic plasticity, Hebbian plasticity describes an activity-induced change in synaptic strength, caused by correlated pre- and postsynaptic activity. Additionally, Hebbian plasticity is characterised by input specificity, which means it takes place only at synapses, which participate in activity. Because of its correlative nature, Hebbian plasticity suggests itself as a mechanism behind associative learning. Although it is commonly assumed that synaptic plasticity is closely linked to synaptic activity during development, the mechanistic understanding of this coupling is far from complete. In the present study channelrhodopsin-2 was used to evoke activity in vivo, at the glutamatergic Drosophila neuromuscular junction. Remarkably, correlated pre- and postsynaptic stimulation led to increased incorporation of GluR-IIA-type glutamate receptors into postsynaptic receptor fields, thus boosting postsynaptic sensitivity. This phenomenon is input-specific. Conversely, GluR-IIA was rapidly removed from synapses at which neurotransmitter release failed to evoke substantial postsynaptic depolarisation. This mechanism might be responsible to tame uncontrolled receptor field growth. Combining these results with developmental GluR-IIA dynamics leads to a comprehensive physiological concept, where Hebbian plasticity guides growth of postsynaptic receptor fields and sparse transmitter release stabilises receptor fields by preventing overgrowth. Additionally, a novel mechanism of retrograde signaling was discovered, where direct postsynaptic channelrhodopsin-2 based stimulation, without involvement of presynaptic neurotransmitter release, leads to presynaptic depression. This phenomenon is reminiscent of a known retrograde homeostatic mechanism, of inverted polarity, where neurotransmitter release is upregulated, upon reduction of postsynaptic sensitivity.},
  subject      = {Synapse},
  language  = {en}
}
@phdthesis{Schlereth2013,
  author    = {Schlereth, Florian},
  title     = {Expression of the DHEA/DHEAS-Shuttle in cell lines and foetal tissue of human liver, adrenal and cartilage},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102068},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {DHEA is a precursor for the male and female sex hormones testosterone and estradiol, which are mainly secreted from the testes and the ovary, respectively. In addition, epidemiological studies showed that low serum levels of DHEA and DHEAS correlate with the incidence of autoimmune disease, cancer and cardiovascular disease. In vitro, DHEA and DHEAS influenced glucose metabolism in a favourable manner. However, positive effects of DHEA substitution were only significant adrenal insufficiency in women. Steroid sulphotransferase 2A1 (SULT2A1) is the responsible enzyme for sulphonation of DHEA to DHEAS which is thought to be the inactive form of DHEA. In this role, SULT2A1 acts as a central regulator of steroid synthesis because sulphonation of DHEA withdraws the substrate for further downstream conversion. Another essential cofactor for sulphonation is PAPS, which is produced by the enzyme PAPS synthase (PAPSS) from ATP and anorganic sulphate. PAPSS exists in the different isoforms PAPSS1 and PAPSS2 and splice variants PAPSS2a and PAPSS2b. Changes in PAPSS activity are thought to influence sulphonation of DHEA significantly. However, neither regulation of PAPSS nor its influence on SULT2A1 have been investigated in human cell lines or humans. The main goal of this thesis was to analyze the enzyme expression of the DHEA/DHEA shuttle, i.e. mRNA and protein of SULT2A1, PAPSS1 and PAPSS2, in various human cell lines. Furthermore, I investigated which cell line could serve as a suitable model for further research regarding regulation of SULT2A1, PAPSS1 and PAPSS2. Here, I could show that the enzymes of the DHEA/DHEAS shuttle were expressed in the human adrenal cell line NCI-h295R as both mRNA and protein. In enzyme assays, I was able to prove conversion of DHEA to DHEAS as well as to different other steroids. However, applying Trilostane, a potent inhibitor of CYP3B, effectively directed conversion of DHEA to DHEAS. Using these findings, future experiments can investigate for example the influence of certain cytokines or endocrine disruptors on expression and activity of PAPSS1/2 and on sulphonation of DHEA. In particular, the relatively equal expression of PAPSS1 and PAPSS2 will enable us to do knock down experiments with siRNA to elucidate how the activity of one enzyme changes when the other one fails. Sulphonation of DHEA by SULT2A1 is thought to happen in the cytoplasm or more precisely in the Golgi apparatus. However, experiments in transfected cells have shown both a cytoplasmatic and a nuclear localisation when both enzymes were expressed at the same time. Immunocytochemistry revealed the same results in the adrenal cell line NCI-h295R, where both enzymes were expressed strongly in the nucleus. The physiological role is not clear and requires further research. Presumably, sulphate is activated in the nucleus. However, one could also speculate that a shift of PAPSS to the nucleus could generate a reservoir, which can be activated by re-localisation to the cytoplasm when more PAPS is needed. Expression of SULT2A1 in some foetal tissues has been investigated earlier. Whilst in adult human cartilage PAPSS1 is predominant, in newly born hamsters PAPSS2 is more abundantly expressed. The expression of PAPSS isoforms in highly sulphonating tissue has not been investigated in humans, so far. This work demonstrated a differential expression of SULT2A1, PAPSS1 and PAPSS2 in adult and foetal liver, adrenal and foetal cartilage tissue. In adult and foetal adrenal expression was similar. However, foetal and adult liver differed in the expression of SULT2A1, which was expressed much more in adult tissue. Most importantly, in foetal cartilage there was only a low expression of SULT2A1 and PAPS seems to mostly provided by PAPSS1, which was considerably higher expressed in cartilage than in other tissues. In contrast, PAPSS2 was mainly expressed in adult and foetal adrenal. Additionally, we reported a case of a female patient who had been investigated for hyperandrogenism. Two mutations in the PAPSS2 gene had led to massively reduced serum levels of DHEAS. One heterozygous mutation in the domain of the APS kinase of the PAPSS2 protein leads to substitution of one amino acid at position 48 (T48R). In vitro experiments showed a residual activity of 6\% for this mutation. A second mutation in the ATP sulphurylase domain of PAPSS2 was found. The introduction of thymidine instead of cytidine leads to a stop codon, which is presumed to truncate the protein at position 329 (R329X). In vitro, no residual activity was seen for this mutation. The lack of PAPS reduces sulphonation of DHEA but also sulphonation of proteoglycanes, which leads to skeletal abnormalities. The abundance of DHEA enables massive downstream conversion to androgens leading to clinical features of hyperandrogenism. Regarding the bone abnormalities, it is interesting and surprising that activity of PAPSS1 compensated to a great extent in cartilage but was not able to keep up a more considerable sulphonation of DHEA. Possibly, the subcellular localisation might play a role in this scenario.},
  subject      = {Dehydroepiandrosteron},
  language  = {en}
}
@phdthesis{Michalska2013,
  author    = {Michalska, Marta},
  title     = {Molecular Imaging of atherosclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73243},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Atherosklerose ist eine aktive und progressive Erkrankung, bei der vaskul{\"a}re Adh{\"a}sionsmolek{\"u}le wie VCAM-1 eine entscheidende Rolle durch Steuerung der Rekrutierung von Immunzellen in den fr{\"u}hen und fortgeschrittenen Plaques spielen. Ein zielgerichteter Einsatz von VCAM-1-Molek{\"u}len mit spezifischen Kontrastmitteln ist daher eine M{\"o}glichkeit, die VCAM-1-Expression zu kontrollieren, Plaquewachstum ab einem fr{\"u}hen Zeitpunkt zu visualisieren und eine fr{\"u}he Pr{\"a}vention von Atherosklerose vor Beginn der Thrombusbildung zu etablieren. Des Weiteren bietet die nichtinvasive Magnetresonanz (MR)-Bildgebung den Vorteil der Kombination molekularer und morphologischer Daten. Sie erm{\"o}glicht, mithilfe von entwickelten VCAM-1-markierten Eisenoxidpartikeln, den spezifischen Nachweis entz{\"u}ndlicher Prozesse w{\"a}hrend der Atherosklerose. Diese Arbeit belegt, dass mit dem VCAM-1-Konzept eine vielversprechende Herangehensweise gefunden wurde und dass das, mit spezifischen superparamagnetischen Eisenoxid (USPIO) konjugierte VCAM-1-Peptid, gegen{\"u}ber unspezifischer USPIOs ein erh{\"o}htes Potenzial bei der Untersuchung der Atherosklerose in sich tr{\"a}gt. Im ersten Teil der Arbeit konnte im Mausmodell gezeigt werden, dass gerade das VCAM-1-Molek{\"u}l ein sinnvoller Ansatzpunkt zur Darstellung und Bildgebung von Atherosklerose ist, da in der fr{\"u}hen Phase der Entz{\"u}ndung die vaskul{\"a}ren Zelladh{\"a}sionsmolek{\"u}le {\"u}berexprimiert und auch kontinuierlich, w{\"a}hrend der fortschreitenden Plaquebildung, hochreguliert werden. Weiterhin beschreibt diese Arbeit die Funktionst{\"u}chtigkeit und das Verm{\"o}gen des neu gestalteten USPIO Kontrastmittels mit dem zyklischen Peptid, in seiner Spezialisierung auf die VCAM-1 Erkennung. Experimentelle Studien mit ultra-Hochfeld-MRT erm{\"o}glichten weitere ex vivo und in vivo Nachweise der eingesetzten USPIO-VCAM-1-Partikel innerhalb der Region um die Aortenwurzel in fr{\"u}hen und fortgeschrittenen atherosklerotischen Plaques von 12 und 30 Wochen alten Apolipoprotein E-defizienten (ApoE-/-) M{\"a}usen. Mit ihrer Kombination aus Histologie und Elektronenmikroskopie zeigt diese Studie zum ersten Mal die Verteilung von VCAM-1-markierten USPIO Partikeln nicht nur in luminalem Bereich der Plaques, sondern auch in tieferen Bereichen der medialen Muskelzellen. Dieser spezifische und sensitive Nachweis der fr{\"u}hen und fortgeschrittenen Stadien der Plaquebildung bringt auf molekularer Ebene neue M{\"o}glichkeiten zur Fr{\"u}herkennung von atherosklerotischen Plaques vor dem Entstehen von 8 Rupturen. Im Gegensatz zum USPIO-VCAM-1-Kontrastmittel scheiterten unspezifische USPIO Partikel an der Identifikation fr{\"u}her Plaqueformen und begrenzten die Visualisierung von Atherosklerose auf fortgeschrittene Stadien in ApoE-/- M{\"a}usen.},
  subject      = {VCAM},
  language  = {en}
}
@article{Jacka2013,
  author    = {Jacka, Felice N.},
  title     = {Nutritional Psychiatry: Inaugural Meeting in Tokyo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101072},
  year      = {2013},
  abstract  = {Welcome to the inaugural meeting of the International Society for Nutritional Psychiatry Research (ISNPR). It is a great pleasure to have the opportunity to join with colleagues working in this new and exciting field of research. Although there has long been interest in the links between nutritional deficiencies and psychiatric illness, as well as interest in the role of food allergies in such illnesses, the last five years has seen a significant and notable growth in this nascent field of research, with an accompanying impact on the viewpoints and practices of scientists and clinicians working in mental health. In my particular field of interest - that of the role of overall dietary quality in the common mental disorders, depression and anxiety - there has been an exponential growth in the literature since the end of 2009. It is exciting and gratifying to see concordant results from across the globe, in young children and adolescents through to older adults, and from countries as diverse as Norway and Taiwan. The study of the efficacy of nutritional interventions in psychiatric illness is also developing rapidly, with high quality randomised controlled trials now being conducted in multiple settings and with outcomes that include cognition as well as depression, bipolar disorder, schizophrenia and anxiety disorders. Another important development in this field is the rapidly growing recognition that nutrition is of central importance in the risk for cognitive decline and dementia. As this new recognition filters through to clinical researchers, I look forward to seeing new interventions in this area. Another area of research with significant interest and activity grows from the understanding of the centrality of physical health to mental health and vice versa. There are many nutrition researchers, dietitians and other health practitioners working to address the physical health of patients with mental illness; acting on the recognition that physical and mental health are closely related and mutually reinforcing. There is no doubt that the formation of an international society is timely; we now have the opportunity to join forces to share knowledge and build important collaborations. Building capacity in this field by sharing our knowledge with students and early career researchers will be another important activity of our society, as will building the credibility of nutritional psychiatry research through a clear understanding and implementation of best practice scientific methodology. I welcome each of you to extend the invitation to join our new ISNPR to colleagues and students in your networks. I would also encourage you to contribute to the discussions and sharing of knowledge by contributing short pieces to our newsletter, which will be disseminated by the end of this year. For those who are unable to attend this year's meeting, we hope that 2014 may present a possibility for attendance. Our aim is conduct our first Annual General Meeting before the end of July 2013 via teleconference and I welcome agenda items from those interested. With very best wishes Felice Jacka President ISNPR},
  subject      = {Omega-3-Fetts{\"a}uren},
  language  = {en}
}
@phdthesis{Leingaertner2013,
  author    = {Leing{\"a}rtner, Annette},
  title     = {Combined effects of climate change and extreme events on plants, arthropods and their interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87758},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {I. Global climate change directly and indirectly influences biotic and abiotic components of ecosystems. Changes in abiotic ecosystem components caused by climate change comprise temperature increases, precipitation changes and more frequently occurring extreme events. Mediated by these abiotic changes, biotic ecosystem components including all living organisms will also change. Expected changes of plants and animals are advanced phenologies and range shifts towards higher latitudes and altitudes which presumably induce changes in species interactions and composition. Altitudinal gradients provide an optimal opportunity for climate change studies, because they serve as natural experiments due to fast changing climatic conditions within short distances. In this dissertation two different approaches were conducted to reveal species and community responses to climate change. First, species richness and community trait analyses along an altitudinal gradient in the Bavarian Alps (chapters II, III) and second, climate change manipulation experiments under different climatic contexts (chapters IV, V, IV). II. We performed biodiversity surveys of butterfly and diurnal moth species on 34 grassland sites along an altitudinal gradient in the National Park Berchtesgaden. Additionally, we analysed the dominance structure of life-history traits in butterfly assemblages along altitude. Species richness of butterflies and diurnal moths decreased with increasing altitude. The dominance of certain life-history-traits changed along the altitudinal gradient with a higher proportion of larger-winged species and species with higher egg numbers towards higher altitudes. However, the mean egg maturation time, population density and geographic distribution within butterfly assemblages decreased with increasing altitude. Our results indicate that butterfly assemblages were mainly shaped by environmental filtering. We conclude that butterfly assemblages at higher altitudes will presumably lack adaptive capacity to future climatic conditions, because of specific trait combinations. III. In addition to butterfly and diurnal moth species richness we also studied plant species richness in combination with pollination type analyses along the altitudinal gradient. The management type of the alpine grasslands was also integrated in the analyses to detect combined effects of climate and management on plant diversity and pollination type. Plant species richness was highest at intermediate altitudes, whereby the management type influenced the plant diversity with more plant species at grazed compared to mown or non-managed grasslands. The pollination type was affected by both the changing climate along the gradient and the management type. These results suggest that extensive grazing can maintain high plant diversity along the whole altitudinal gradient. With ongoing climate change the diversity peak of plants may shift upwards, which can cause a decrease in biodiversity due to reduced grassland area but also changes in species composition and adaptive potential of pollination types. IV. We set up manipulation experiments on 15 grassland sites along the altitudinal gradient in order to determine the combined effects of extreme climatic events (extreme drought, advanced and delayed snowmelt) and elevation on the nutritional quality and herbivory rates of alpine plants. The leaf CN (carbon to nitrogen) ratio and the plant damage through herbivores were not significantly affected by the simulated extreme events. However, elevation influenced the CN ratios and herbivory rates of alpine plants with contrasting responses between plant guilds. Furthermore, we found differences in nitrogen concentrations and herbivory rates between grasses, legumes and forbs, whereas legumes had the highest nitrogen concentrations and were damaged most. Additionally, CN ratios and herbivory rates increased during the growing season, indicating a decrease of food plant quality during the growing season. Contrasting altitudinal responses of grasses, legumes and forbs presumably can change the dominance structure among these plant guilds with ongoing climate change. V. In this study we analysed the phenological responses of grassland species to an extreme drought event, advanced and delayed snowmelt along the altitudinal gradient. Advanced snowmelt caused an advanced beginning of flowering, whereas this effect was more pronounced at higher than at lower altitudes. Extreme drought and delayed snowmelt had rather low effects on the flower phenology and the responses did not differ between higher and lower sites. The strongest effect influencing flower phenology was altitude, with a declining effect through the season. The length of flowering duration was not significantly influenced by treatments. Our data suggest that plant species at higher altitudes may be more affected by changes in snowmelt timing in contrast to lowland species, as at higher altitudes more severe changes are expected. However, the risk of extreme drought events on flowering phenology seems to be low. VI. We established soil-emergence traps on the advanced snowmelt and control treatment plots in order to detect possible changes in abundances and emergence phenologies of five arthropod orders due to elevation and treatment. Additionally, we analysed the responses of Coleoptera species richness to elevation and treatment. We found that the abundance and species richness of Coleoptera increased with elevation as well as the abundance of Diptera. However, the abundance of Hemiptera decreased with elevation and the abundances of Araneae and Hymenoptera showed no elevational patterns. The advanced snowmelt treatment increased the abundances of Araneae and Hymenoptera. The emergence of soil-hibernating arthropods was delayed up to seven weeks at higher elevations, whereas advanced snowmelt did not influence the emergence phenology of arthropods immediately after snowmelt. With climate change earlier snowmelt will occur more often, which especially will affect soil-hibernating arthropods in alpine regions and may cause desynchronisations between species interactions. VII. In conclusion, we showed that alpine ecosystems are sensitive towards changing climate conditions and extreme events and that many alpine species in the Bavarian Alps are endangered. Many alpine species could exist under warmer climatic conditions, however they are expected to be outcompeted by more competitive lowland species. Furthermore, host-parasite or predator-prey interactions can be disrupted due to different responses of certain guilds to climate change. Understanding and predicting the complex dynamics and potential risks of future climate change remains a great challenge and therefore further studies analysing species and community responses to climate change are needed.},
  subject      = {Insekten},
  language  = {en}
}
@phdthesis{FlatenAndersen2013,
  author    = {Fl{\aa}ten Andersen, Hanne},
  title     = {New Materials for Lithium-Ion Batteries},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101434},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Over the last decades, lithium-ion batteries have grown more important and substituted other energy storage systems. Due to advantages such as high energy density and low self-discharge, the lithium-ion battery has taken its part in the rechargeable energy storage market, and it is now found in most laptops, cameras and mobile phones. With the increasing demands for electrical vehicles and stationary energy storage systems, there is a necessity for improved lithium-ion battery materials. In this thesis several alternative electrode materials have been examined with a main focus on the electrochemical characterisation. As an alternative to the commercial cathode LiCoO2, the LiMn2O4 cathode has been suggested due to its reduced toxicity, material abundance, reduced costs and increased specific capacity. On the anode side, several Sn-containing anodes have been investigated and steps to overcome the main challenge, the great volume expansion upon cycling, have been taken. In addition, a novel anode material group was synthesised at the University of Marburg and two substances of the lithium chalcogenidometalate networks were successfully characterised. The cathode material, LiMn2O4, was synthesised via the sol-gel technique and several coating methods such as dip-coating, electrophoretics and infiltration were investigated. The LiMn2O4 material was initially coated on a porous metal foam as a current collector, thus providing new possibilities as the porosity of the substrate increased, mechanical stability and adhesion improved and a 3-dimensional network was obtained. In order to compare the results of the LiMn2O4 cathode material on the novel current collector, the material was also coated on a standard metallic foil and characterised. The analysis followed via X-ray diffraction, electron microscopy, thermogravimetrical analysis and several electrochemical techniques. Tin containing anode materials were chosen due to the doubling of the theoretical capacity compared with the commercially used graphite. However, a great challenge lies with using tin or tin-containing anode materials. Upon lithiation of Sn, the material can expand up to 300 \%, therefore a stabilising effect is necessary to avoid a collapse of the material. This work shows several new concepts and attempts to overcome this challenge, including SnO2 nanowires deposited via chemical vapour deposition on both metallic foam and standard current collectors. A new improvement consisted of the tin - carbon nanofibers where the nanofibers form a stabilising matrix that can partially buffer the volume change of the Sn particles. The synthesis of the Sn-containing anodes took place at the University of Cologne, while characterisation, cell preparation and optimising the electrode system were features of this thesis. In addition, a lithium chalcogenidometalate network proved to be an interesting, new anode material group. Both Li4MnSn2Se7 and Li4MnGe2S7 (synthesised at Philipps-Universit{\"a}t Marburg) were electrochemically examined to better understand the lithiation processes. Both materials obtained very high specific capacities and were found to be possible alternatives to the state-of-the art anodes. All the examined electrode materials were found to have some advantage over the commercially used LiCoO2 and graphite electrodes, and a thorough characterization of the materials was performed to understand the processes that took place.},
  subject      = {Lithium-Ionen-Akkumulator},
  language  = {en}
}
@phdthesis{Wangorsch2013,
  author    = {Wangorsch, Gaby},
  title     = {Mathematical modeling of cellular signal transduction},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87746},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {A subtly regulated and controlled course of cellular processes is essential for the healthy functioning not only of single cells, but also of organs being constituted thereof. In return, this entails the proper functioning of the whole organism. This implies a complex intra- and inter-cellular communication and signal processing that require equally multi-faceted methods to describe and investigate the underlying processes. Within the scope of this thesis, mathematical modeling of cellular signaling finds its application in the analysis of cellular processes and signaling cascades in different organisms. ...},
  subject      = {Mathematische Modellierung},
  language  = {en}
}
@phdthesis{Dietz2013,
  author    = {Dietz, Andreas},
  title     = {Central Asian Snow Cover Characteristics between 1986 and 2012 derived from Time Series of Medium Resolution Remote Sensing Data},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-101221},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {The eminent importance of snow cover for climatic, hydrologic, anthropogenic, and economic reasons has been widely discussed in scientific literature. Up to 50\% of the Northern Hemisphere is covered by snow at least temporarily, turning snow to the most prevalent land cover types at all. Depending on regular precipitation and temperatures below freezing point it is obvious that a changing climate effects snow cover characteristics fundamentally. Such changes can have severe impacts on local, national, and even global scale. The region of Central Asia is not an exception from this general rule, but are the consequences accompanying past, present, and possible future changes in snow cover parameters of particular importance. Being characterized by continental climate with hot and dry summers most precipitation accumulates during winter and spring months in the form of snow. The population in this 4,000,000 km² vast area is strongly depending on irrigation to facilitate agriculture. Additionally, electricity is often generated by hydroelectric power stations. A large proportion of the employed water originates from snow melt during spring months, implying that changes in snow cover characteristics will automatically affect both the total amount of obtainable water and the time when this water becomes available. The presented thesis explores the question how the spatial extent of snow covered surface has evolved since the year 1986. This investigation is based on the processing of medium resolution remote sensing data originating from daily MODIS and AVHRR sensors, thus forming a unique approach of snow cover analysis in terms of temporal and spatial resolution. Not only duration but also onset and melt of snow coverage are tracked over time, analyzing for systematic changes within this 26 years lasting time span. AVHRR data are processed from raw Level 1B orbit data to Level 3 thematic snow cover products. Both, AVHRR and MODIS snow maps undergo a further post-processing, producing daily full-area mosaics while completely eliminating inherent cloud cover. Snow cover parameters are derived based on these daily and cloud-free time series, allowing for a detailed analysis of current status and changes. The results confirm the predictions made by coarse resolution predictions from climate models: Central Asian snow cover is changing, posing new challenges for the ecosystem and future water supply. The changes, however, are not aimed at only one direction. Regions with decreasing snow cover exist as well as those where the duration of snow cover increases. A shift towards earlier snow cover start and melt can be observed, posing a serious challenge to water management authorities due to a changed runoff regime.},
  subject      = {Zentralasien},
  language  = {en}
}
@phdthesis{Hess2013,
  author    = {Heß, Michael},
  title     = {Vaccinia virus-encoded bacterial beta-glucuronidase as a diagnostic biomarker for oncolytic virotherapy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86789},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Oncolytic virotherapy represents a promising approach to revolutionize cancer therapy. Several preclinical and clinical trials display the safety of oncolytic viruses as wells as their efficiency against solid tumors. The development of complementary diagnosis and monitoring concepts as well as the optimization of anti-tumor activity are key points of current virotherapy research. Within the framework of this thesis, the diagnostic and therapeutic prospects of beta-glucuronidase expressed by the oncolytic vaccinia virus strain GLV-1h68 were evaluated. In this regard, a beta-glucuronidase-based, therapy-accompanying biomarker test was established which is currently under clinical validation. By using fluorescent substrates, the activity of virally expressed beta-glucuronidase could be detected and quantified. Thereby conclusions about the replication kinetics of oncolytic viruses in animal models and virus-induced cancer cell lysis could be drawn. These findings finally led to the elaboration and establishment of a versatile biomarker assay which allows statements regarding the replication of oncolytic viruses in mice based on serum samples. Besides the analysis of retrospective conditions, this test is able to serve as therapy-accompanying monitoring tool for virotherapy approaches with beta-glucuronidase-expressing viruses. The newly developed assay also served as complement to routinely used plaque assays as well as reference for virally expressed anti-angiogenic antibodies in additional preclinical studies. Further validation of this biomarker test is currently taking place in the context of clinical trials with GL-ONC1 (clinical grade GLV-1h68) and has already shown promising preliminary results. It was furthermore demonstrated that fluorogenic substrates in combination with beta-glucuronidase expressed by oncolytic viruses facilitated the optical detection of solid tumors in preclinical models. In addition to diagnostic purposes, virus-encoded enzymes could also be combined with prodrugs resulting in an improved therapeutic outcome of oncolytic virotherapy. In further studies, the visualization of virus-induced immune reactions as well as the establishment of innovative concepts to improve the therapeutic outcome of oncolytic virotherapy could be accomplished. In conclusion, the results of this thesis provide crucial findings about the influence of virally expressed beta-glucuronidase on various diagnostic concepts in the context of oncolytic virotherapy. In addition, innovative monitoring and therapeutic strategies could be established. Our preclinical findings have important clinical influence, particularly by the development of a therapy-associated biomarker assay which is currently used in different clinical trials.},
  subject      = {Vaccinia-Virus},
  language  = {en}
}
@phdthesis{Wismer2013,
  author    = {Wismer, Sebastian},
  title     = {Essays in Industrial Organization: Intermediation, Marketing, and Strategic Pricing},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-99102},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {This dissertation deals with certain business strategies that have become particularly relevant with the spread and development of new information technologies. The introduction explains the motivation, discusses different ways of defining the term "two-sided market", and briefly summarizes the subsequent essays. The first essay examines the effects of product information on the pricing and advertising decision of a seller who offers an experience good whose quality is unknown to consumers prior to purchase. It comprises of two theoretical models which differ with respect to their view on advertising. The analysis addresses the question how the availability of additional, potentially misleading information affects the seller's quality-dependent pricing and advertising decision. In the first model, in which both advertising and product reviews make consumers aware about product existence, the seller's optimal price turns out to be increasing in product quality. However, under certain circumstances, also the seller of a low-quality product prefers setting a high price. Within the given framework, the relationship between product quality and advertising depends on the particular parameter constellation. In the second model, some consumers are assumed to interpret price as a signal of quality, while others rely on information provided by product reviews. Consequently, and differently from the first part, pricing may indirectly inform consumers about product quality. On the one hand, in spite of asymmetric information on product quality, equilibria exist that feature full information pricing, which is in line with previous results presented by the signaling literature. On the other hand, potentially misleading product reviews may rationalize further pricing patterns. Moreover, assuming that firms can manipulate product reviews by investing in concealed marketing, equilibria can arise in which a high price signals low product quality. However, in these extreme cases, only a few (credulous) consumers consider buying the product. The second essay deals with trade platforms whose operators not only allow sellers to offer their products to consumers, but also offer products themselves. In this context, the platform operator faces a hold-up problem if he sets classical two-part tariffs (on which previous literature on two-sided markets focussed) as potential competition between the platform operator and sellers reduces platform attractiveness. Since some sellers refuse to join the platform, products whose existence is not known to the platform operator in the first place and which can only be established by better informed sellers may not be offered at all. However, revenue-based fees lower the platform operator's incentives to compete with sellers, increasing platform attractiveness. Therefore, charging such proportional fees can be profitable, what may explain why several trade platforms indeed do charge proportional fees. The third essay examines settings in which sellers can be active both on an intermediary's trade platform and in other sales channels. It explores the sellers' incentives to set different prices across sales channels within the given setup. Afterwards, it analyzes the intermediary's tariff decision, taking into account the implications on consumers' choice between different sales channels. The analysis particularly focusses on the effects of a no-discrimination rule which several intermediaries impose, but which appears to be controversial from a competition policy view. It identifies under which circumstances the intermediary prefers restricting sellers' pricing decisions by imposing a no-discrimination rule, attaining direct control over the split-up of customers on sales channels. Moreover, it illustrates that such rules can have both positive and negative effects on welfare within the given framework.},
  subject      = {Industrie{\"o}konomie},
  language  = {en}
}
@phdthesis{Kuehn2013,
  author    = {K{\"u}hn, Andrea},
  title     = {The molecular interplay of proteins expressed in the sexual stages and the induction of gamete formation in the malaria parasite Plasmodium falciparum},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-98028},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Transmission of the malaria parasite from man to the mosquito requires the formation of sexual parasite stages, the gametocytes. The gametocytes are the only parasite stage that is able to survive in the mosquito midgut and to undergo further development - gamete formation and fertilization. Numerous sexual stage-specific proteins have been discovered, some of which play crucial roles for parasite transmission. However, the functions of many sexual stage proteins remain elusive. Amongst the sexual stage-specific proteins are the proteins of the PfCCp proteins family, which exhibit numerous adhesion domains in their protein structures. For four members of the protein family, PfCCp1 to PfCCp4 gene-disruptant parasite lines had been already studied. Amongst these, PfCCp2 and PfCCp3 showed an important role for development of the parasites in the mosquito. In the present work the study of gene-disrupted parasites of the PfCCp Protein family was completed. PfCCp5-KO and PfFNPA-KO parasite lines were characterized to a great extent and many properties were similar to those of other PfCCp proteins. The co-dependent expression previously reported to be a phenomenon of PfCCp proteins was also observed in these two mutants, although to lesser extent. When either PfCCp5 or PfFNPA were absent, all other proteins were detected in reduced abundance only. Co-dependent expression manifests exclusively on the protein level. Transcript levels were not altered as RT-PCR showed. Amongst PfCCp proteins numerous proteinproteins interactions are taking place. The previously described multimeric protein complexes also include further sexual stage-specific proteins like Pfs230, Pfs48/45 and Pfs25. Recently, a new component of PfCCp-based multimeric protein complexes had been identified. The protein was named PfWLP1 (WD repeat protein-like protein 1) due to its possession of several WD40 repeats. In the present study expression of this uncharacterized protein was investigated via indirect IFA. It was expressed in asexual blood stages and gametocytes. Upon gamete formation and fertilization its expression ceased. Another sexual stage protein studied in this work was PfactinII. It was shown to be exclusively expressed in sexual stages. In gametocytes it co-localizes with Pfs230 and correct localization of PfactinII depends on presence of Pfs230. Transcript analysis by means of RT-PCR revealed the expression of several components of the IMC in gametocytes. Furthermore, five or six myosin genes encoded in the P. falciparum genome were detected in gametocytes. Gametocyte egress was studied on the ultrastructural level via transmission electron microscopy and an inside-out type of egress was observed. Firstly, the membrane of the parasitophorous vacuole (PVM) was lysed and only thereafter the membrane of the red blood cell (RBCM) ruptured. Furthermore, a new inductor of gametogenesis was identified: The K+/H+ ionophore nigericin induced gametocytes activation in the absence of xanthurenic acid (XA), which is responsible for gamtetocyte activation in the mosquito midgut. Selective permeabilization of RBCM and PVM by the mild detergent saponin, showed that in the absence of these membranes male gametocytes were still able to perceive both XA and the drop in temperature. Thus, the receptors for both factors signaling the parasite transmission to the mosquito, seem to be of parasitic origin. LC/MS/MS analysis confirmed the ability of RBCs to take up XA. With malaria eradication on the agenda of malaria research targeting the sexual stages becomes a crucial part of intervention strategies. The sexual stages are especially attractive target as they represent a population bottleneck. The here reported findings on P. falciparum gametocytes provide several potential candidate proteins for developing tools to interrupt transmission from man to mosquito. Such tools might include Transmission blocking vaccines and drugs.},
  subject      = {Malaria},
  language  = {en}
}
@inproceedings{OPUS4-9740,
  title     = {Media Psychology - "Media Research: Yesterday, Today, and Tomorrow" Proceedings of the 8th Conference of the Media Psychology Division of the German Psychological Society},
  editor    = {Schwab, Frank and Carolus, Astrid and Brill, Michael and Hennighausen, Christine},
  isbn      = {978-3-923959-93-8},
  doi       = {10.25972/OPUS-9740},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97403},
  pages     = {105},
  year      = {2013},
  abstract  = {The proceedings of the 8th Conference of the Media Psychology Division of the German Psychological Society hosted by the University of Wuerzburg from the 4th until the 6th of September 2013 contains the abstracts of the conference participants. Following the motto of the conference "Media Research: Yesterday, Today, and Tomorrow" a large number of media-psychological topics was dealt with. Amongst others, participants presented their research on interactive learning, emotions, virtual agents and avatars, gaming, scientific communication, politics, motion pictures and entertainment, social media, methods, and persuasions.},
  subject      = {Deutsche Gesellschaft f{\"u}r Psychologie / Fachgruppe Medienpsychologie},
  language  = {en}
}
@phdthesis{Christ2013,
  author    = {Christ, Thomas},
  title     = {Value-distribution of the Riemann zeta-function and related functions near the critical line},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97763},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {The Riemann zeta-function forms a central object in multiplicative number theory; its value-distribution encodes deep arithmetic properties of the prime numbers. Here, a crucial role is assigned to the analytic behavior of the zeta-function on the so called critical line. In this thesis we study the value-distribution of the Riemann zeta-function near and on the critical line. Amongst others we focus on the following. PART I: A modified concept of universality, a-points near the critical line and a denseness conjecture attributed to Ramachandra. The critical line is a natural boundary of the Voronin-type universality property of the Riemann zeta-function. We modify Voronin's concept by adding a scaling factor to the vertical shifts that appear in Voronin's universality theorem and investigate whether this modified concept is appropriate to keep up a certain universality property of the Riemann zeta-function near and on the critical line. It turns out that it is mainly the functional equation of the Riemann zeta-function that restricts the set of functions which can be approximated by this modified concept around the critical line. Levinson showed that almost all a-points of the Riemann zeta-function lie in a certain funnel-shaped region around the critical line. We complement Levinson's result: Relying on arguments of the theory of normal families and the notion of filling discs, we detect a-points in this region which are very close to the critical line. According to a folklore conjecture (often attributed to Ramachandra) one expects that the values of the Riemann zeta-function on the critical line lie dense in the complex numbers. We show that there are certain curves which approach the critical line asymptotically and have the property that the values of the zeta-function on these curves are dense in the complex numbers. Many of our results in part I are independent of the Euler product representation of the Riemann zeta-function and apply for meromorphic functions that satisfy a Riemann-type functional equation in general. PART II: Discrete and continuous moments. The Lindel{\"o}f hypothesis deals with the growth behavior of the Riemann zeta-function on the critical line. Due to classical works by Hardy and Littlewood, the Lindel{\"o}f hypothesis can be reformulated in terms of power moments to the right of the critical line. Tanaka showed recently that the expected asymptotic formulas for these power moments are true in a certain measure-theoretical sense; roughly speaking he omits a set of Banach density zero from the path of integration of these moments. We provide a discrete and integrated version of Tanaka's result and extend it to a large class of Dirichlet series connected to the Riemann zeta-function.},
  subject      = {Riemannsche Zetafunktion},
  language  = {en}
}
@article{LinsenmannMonoranuKessleretal.2013,
  author    = {Linsenmann, Thomas and Monoranu, Camelia M. and Kessler, Almuth F. and Ernestus, Ralf I. and Westermaier, Thomas},
  title     = {Bone chips, fibrin glue, and osteogeneration following lateral suboccipital craniectomy: a case report},
  series = {BMC Research Notes},
  journal   = {BMC Research Notes},
  doi       = {10.1186/1756-0500-6-523},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97346},
  year      = {2013},
  abstract  = {Background Suboccipital craniectomy is a conventional approach for exploring cerebellopontine angle lesions. A variety of techniques have been successfully employed to reconstruct a craniectomy. This is the first report about the histological findings after performing a cranioplasty by using a mixture of autologous bone chips and human allogenic fibrin glue. Case presentation A 53-year-old German woman underwent left lateral suboccipital retrosigmoidal craniectomy for treatment of trigeminal neuralgia in 2008. Cranioplasty was perfomed by using a mixture of autologous bone chips and human allogenic fibrin glue. Due to recurrent neuralgia, a second left lateral suboccipital craniectomy was performed in 2012. The intraoperative findings revealed a complete ossification of the former craniotomy including widely mature trabecular bone tissue in the histological examination. Conclusion A mixture of autologous bone chips and human allogenic fibrin glue seems to provide sufficient bone-regeneration revealed by histological and neuroradiological examinations.},
  language  = {en}
}
@article{BuschTschernitzThurneretal.2013,
  author    = {Busch, Albert and Tschernitz, Sebastian and Thurner, Anette and Kellersmann, Richard and Lorenz, Udo},
  title     = {Fatal Paraneoplastic Embolisms in Both Circulations in a Patient with Poorly Differentiated Neuroendocrine Tumour},
  series = {Case Reports in Vascular Medicine},
  journal   = {Case Reports in Vascular Medicine},
  doi       = {10.1155/2013/739427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97335},
  year      = {2013},
  abstract  = {Arterial embolism with lower limb ischemia is a rare manifestation of paraneoplastic hypercoagulability in cancer patients. We report a unique case of fatal thromboembolism involving both circulations associated with a poorly differentiated neuroendocrine tumor of the lung with rapid progress despite high doses of unfractioned heparin and review the current literature on anticoagulative regimen in tumour patients.},
  language  = {en}
}
@article{KneitzKalogirouSpahnetal.2013,
  author    = {Kneitz, Burkhard and Kalogirou, Charis and Spahn, Martin and Krebs, Markus and Joniau, Steven and Lerut, Evelyne and Burger, Maximilian and Scholz, Claus-J{\"u}rgen and Kneitz, Susanne and Riedmiller, Hubertus},
  title     = {MiR-205 Is Progressively Down-Regulated in Lymph Node Metastasis but Fails as a Prognostic Biomarker in High-Risk Prostate Cancer},
  series = {International Journal of Molecular Sciences},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms141121414},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97321},
  year      = {2013},
  abstract  = {The treatment of high-risk prostate cancer (HRPCa) is a tremendous challenge for uro-oncologists. The identification of predictive moleculobiological markers allowing risk assessment of lymph node metastasis and systemic progression is essential in establishing effective treatment. In the current study, we investigate the prognostic potential of miR-205 in HRPCa study and validation cohorts, setting defined clinical endpoints for both. We demonstrate miR-205 to be significantly down-regulated in over 70\% of the HRPCa samples analysed and that reconstitution of miR-205 causes inhibition of proliferation and invasiveness in prostate cancer (PCa) cell lines. Additionally, miR-205 is increasingly down-regulated in lymph node metastases compared to the primary tumour indicating that miR-205 plays a role in migration of PCa cells from the original location into extraprostatic tissue. Nevertheless, down-regulation of miR-205 in primary PCa was not correlated to the synchronous presence of metastasis and failed to predict the outcome for HRPCa patients. Moreover, we found a tendency for miR-205 up-regulation to correlate with an adverse outcome of PCa patients suggesting a pivotal role of miR-205 in tumourigenesis. Overall, we showed that miR-205 is involved in the development and metastasis of PCa, but failed to work as a useful clinical biomarker in HRPCa. These findings might have implications for the use of miR-205 as a prognostic or therapeutic target in HRPCa.},
  language  = {en}
}
@article{BodemRethwilm2013,
  author    = {Bodem, Jochen and Rethwilm, Axel},
  title     = {Evolution of Foamy Viruses: The Most Ancient of All Retroviruses},
  series = {Viruses},
  journal   = {Viruses},
  doi       = {10.3390/v5102349},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97312},
  year      = {2013},
  abstract  = {Recent evidence indicates that foamy viruses (FVs) are the oldest retroviruses (RVs) that we know and coevolved with their hosts for several hundred million years. This coevolution may have contributed to the non-pathogenicity of FVs, an important factor in development of foamy viral vectors in gene therapy. However, various questions on the molecular evolution of FVs remain still unanswered. The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal. Furthermore, animal studies might reveal important issues, such as the identification of the FV in vivo target cells, which than require a detailed characterization, to resolve the molecular basis of the accuracy with which FVs copy their genome. The issues of the extent of FV viremia and of the nature of the virion genome (RNA vs. DNA) also need to be experimentally addressed.},
  language  = {en}
}
@article{KellerGrimmerSteffanDewenter2013,
  author    = {Keller, Alexander and Grimmer, Gudrun and Steffan-Dewenter, Ingolf},
  title     = {Diverse Microbiota Identified in Whole Intact Nest Chambers of the Red Mason Bee Osmia bicornis (Linnaeus 1758)},
  series = {PLoS One},
  journal   = {PLoS One},
  doi       = {10.1371/journal.pone.0078296},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97305},
  year      = {2013},
  abstract  = {Microbial activity is known to have profound impact on bee ecology and physiology, both by beneficial and pathogenic effects. Most information about such associations is available for colony-building organisms, and especially the honey bee. There, active manipulations through worker bees result in a restricted diversity of microbes present within the colony environment. Microbial diversity in solitary bee nests remains unstudied, although their larvae face a very different situation compared with social bees by growing up in isolated compartments. Here, we assessed the microbiota present in nests and pre-adults of Osmia bicornis, the red mason bee, by culture-independent pyrosequencing. We found high bacterial diversity not comparable with honey bee colonies. We identified a variety of bacteria potentially with positive or negative interactions for bee larvae. However, most of the other diverse bacteria present in the nests seem to originate from environmental sources through incorporated nest building material and stored pollen. This diversity of microorganisms may cause severe larval mortality and require specific physiological or symbiotic adaptations against microbial threats. They may however also profit from such a diverse environment through gain of mutualistic partners. We conclude that further studies of microbiota interaction in solitary bees will improve the understanding of fitness components and populations dynamics.},
  language  = {en}
}
@article{ManishNueckelMuehlbergeretal.2013,
  author    = {Manish, Asthana and Nueckel, Katharina and M{\"u}hlberger, Andreas and Neueder, Dorothea and Polak, Thomas and Domschke, Katharina and Deckert, J{\"u}rgen and Herrmann, Martin J.},
  title     = {Effects of transcranial direct current stimulation on consolidation of fear memory},
  series = {Frontiers in Neuropsychiatric Imaging and Stimulation},
  journal   = {Frontiers in Neuropsychiatric Imaging and Stimulation},
  doi       = {10.3389/fpsyt.2013.00107},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97294},
  year      = {2013},
  abstract  = {It has been shown that applying transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) influences declarative memory processes. This study investigates the efficacy of tDCS on emotional memory consolidation, especially experimental fear conditioning. We applied an auditory fear-conditioning paradigm, in which two differently colored squares (blue and yellow) were presented as conditioned stimuli (CS) and an auditory stimulus as unconditioned stimulus (UCS). Sixty-nine participants were randomly assigned into three groups: anodal, cathodal, and sham stimulation. The participants of the two active groups (i.e., anodal and cathodal) received tDCS over the left DLPFC for 12 min after fear conditioning. The effect of fear conditioning and consolidation (24 h later) was measured by assessing the skin conductance response (SCR) to the CS. The results provide evidence that cathodal stimulation of the left DLPFC leads to an inhibitory effect on fear memory consolidation compared to anodal and sham stimulation, as indicated by decreased SCRs to CS+ presentation during extinction training at day 2. In conclusion, current work suggests that cathodal stimulation interferes with processes of fear memory consolidation.},
  language  = {en}
}
@article{MorschhaeuserRamirezZavalaWeyleretal.2013,
  author    = {Morschh{\"a}user, Joachim and Ram{\´i}rez-Zavala, Bernardo and Weyler, Michael and Gildor, Tsvia and Schmauch, Christian and Kornitzer, Daniel and Arkowitz, Robert},
  title     = {Activation of the Cph1-Dependent MAP Kinase Signaling Pathway Induces White-Opaque Switching in Candida albicans},
  series = {PLoS Pathogens},
  journal   = {PLoS Pathogens},
  doi       = {10.1371/journal.ppat.1003696},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97281},
  year      = {2013},
  abstract  = {Depending on the environmental conditions, the pathogenic yeast Candida albicans can undergo different developmental programs, which are controlled by dedicated transcription factors and upstream signaling pathways. C. albicans strains that are homozygous at the mating type locus can switch from the normal yeast form (white) to an elongated cell type (opaque), which is the mating-competent form of this fungus. Both white and opaque cells use the Ste11-Hst7-Cek1/Cek2 MAP kinase signaling pathway to react to the presence of mating pheromone. However, while opaque cells employ the transcription factor Cph1 to induce the mating response, white cells recruit a different downstream transcription factor, Tec1, to promote the formation of a biofilm that facilitates mating of opaque cells in the population. The switch from the white to the opaque cell form is itself induced by environmental signals that result in the upregulation of the transcription factor Wor1, the master regulator of white-opaque switching. To get insight into the upstream signaling pathways controlling the switch, we expressed all C. albicans protein kinases from a tetracycline-inducible promoter in a switching-competent strain. Screening of this library of strains showed that a hyperactive form of Ste11 lacking its N-terminal domain (Ste11ΔN467) efficiently stimulated white cells to switch to the opaque phase, a behavior that did not occur in response to pheromone. Ste11ΔN467-induced switching specifically required the downstream MAP kinase Cek1 and its target transcription factor Cph1, but not Cek2 and Tec1, and forced expression of Cph1 also promoted white-opaque switching in a Wor1-dependent manner. Therefore, depending on the activation mechanism, components of the pheromone-responsive MAP kinase pathway can be reconnected to stimulate an alternative developmental program, switching of white cells to the mating-competent opaque phase.},
  language  = {en}
}
@article{BiehlEhlisMuelleretal.2013,
  author    = {Biehl, Stefanie C. and Ehlis, Ann-Christine and M{\"u}ller, Laura D. and Niklaus, Andrea and Pauli, Paul and Herrmann, Martin J.},
  title     = {The impact of task relevance and degree of distraction on stimulus processing},
  series = {BMC Neuroscience},
  journal   = {BMC Neuroscience},
  doi       = {10.1186/1471-2202-14-107},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97271},
  year      = {2013},
  abstract  = {Background The impact of task relevance on event-related potential amplitudes of early visual processing was previously demonstrated. Study designs, however, differ greatly, not allowing simultaneous investigation of how both degree of distraction and task relevance influence processing variations. In our study, we combined different features of previous tasks. We used a modified 1-back task in which task relevant and task irrelevant stimuli were alternately presented. The task irrelevant stimuli could be from the same or from a different category as the task relevant stimuli, thereby producing high and low distracting task irrelevant stimuli. In addition, the paradigm comprised a passive viewing condition. Thus, our paradigm enabled us to compare the processing of task relevant stimuli, task irrelevant stimuli with differing degrees of distraction, and passively viewed stimuli. EEG data from twenty participants was collected and mean P100 and N170 amplitudes were analyzed. Furthermore, a potential connection of stimulus processing and symptoms of attention deficit hyperactivity disorder (ADHD) was investigated. Results Our results show a modulation of peak N170 amplitudes by task relevance. N170 amplitudes to task relevant stimuli were significantly higher than to high distracting task irrelevant or passively viewed stimuli. In addition, amplitudes to low distracting task irrelevant stimuli were significantly higher than to high distracting stimuli. N170 amplitudes to passively viewed stimuli were not significantly different from either kind of task irrelevant stimuli. Participants with more symptoms of hyperactivity and impulsivity showed decreased N170 amplitudes across all task conditions. On a behavioral level, lower N170 enhancement efficiency was significantly correlated with false alarm responses. Conclusions Our results point to a processing enhancement of task relevant stimuli. Unlike P100 amplitudes, N170 amplitudes were strongly influenced by enhancement and enhancement efficiency seemed to have direct behavioral consequences. These findings have potential implications for models of clinical disorders affecting selective attention, especially ADHD.},
  language  = {en}
}
@article{HalderRufFurdeaetal.2013,
  author    = {Halder, Sebastian and Ruf, Carolin Anne and Furdea, Adrian and Pasqualotto, Emanuele and De Massari, Daniele and van der Heiden, Linda and Bogdan, Martin and Rosenstiel, Wolfgang and Birbaumer, Niels and K{\"u}bler, Andrea and Matuz, Tamara},
  title     = {Prediction of P300 BCI Aptitude in Severe Motor Impairment},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0076148},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97268},
  year      = {2013},
  abstract  = {Brain-computer interfaces (BCIs) provide a non-muscular communication channel for persons with severe motor impairments. Previous studies have shown that the aptitude with which a BCI can be controlled varies from person to person. A reliable predictor of performance could facilitate selection of a suitable BCI paradigm. Eleven severely motor impaired participants performed three sessions of a P300 BCI web browsing task. Before each session auditory oddball data were collected to predict the BCI aptitude of the participants exhibited in the current session. We found a strong relationship of early positive and negative potentials around 200 ms (elicited with the auditory oddball task) with performance. The amplitude of the P2 (r = -0.77) and of the N2 (r = -0.86) had the strongest correlations. Aptitude prediction using an auditory oddball was successful. The finding that the N2 amplitude is a stronger predictor of performance than P3 amplitude was reproduced after initially showing this effect with a healthy sample of BCI users. This will reduce strain on the end-users by minimizing the time needed to find suitable paradigms and inspire new approaches to improve performance.},
  language  = {en}
}
@article{WiegeringPfannUtheetal.2013,
  author    = {Wiegering, Armin and Pfann, Christina and Uthe, Friedrich Wilhelm and Otto, Christoph and Rycak, Lukas and M{\"a}der, Uwe and Gasser, Martin and Waaga-Gasser, Anna-Maria and Eilers, Martin and Germer, Christoph-Thomas},
  title     = {CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97252},
  year      = {2013},
  abstract  = {The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer.},
  language  = {en}
}
@article{ChopraLangSalzmannetal.2013,
  author    = {Chopra, Martin and Lang, Isabell and Salzmann, Steffen and Pachel, Christina and Kraus, Sabrina and B{\"a}uerlein, Carina A. and Brede, Christian and Jord{\´a}n Garrote, Ana-Laura and Mattenheimer, Katharina and Ritz, Miriam and Schwinn, Stefanie and Graf, Carolin and Sch{\"a}fer, Viktoria and Frantz, Stefan and Einsele, Hermann and Wajant, Harald and Beilhack, Andreas},
  title     = {Tumor Necrosis Factor Induces Tumor Promoting and Anti-Tumoral Effects on Pancreatic Cancer via TNFR1},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075737},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97246},
  year      = {2013},
  abstract  = {Multiple activities are ascribed to the cytokine tumor necrosis factor (TNF) in health and disease. In particular, TNF was shown to affect carcinogenesis in multiple ways. This cytokine acts via the activation of two cell surface receptors, TNFR1, which is associated with inflammation, and TNFR2, which was shown to cause anti-inflammatory signaling. We assessed the effects of TNF and its two receptors on the progression of pancreatic cancer by in vivo bioluminescence imaging in a syngeneic orthotopic tumor mouse model with Panc02 cells. Mice deficient for TNFR1 were unable to spontaneously reject Panc02 tumors and furthermore displayed enhanced tumor progression. In contrast, a fraction of wild type (37.5\%), TNF deficient (12.5\%), and TNFR2 deficient mice (22.2\%) were able to fully reject the tumor within two weeks. Pancreatic tumors in TNFR1 deficient mice displayed increased vascular density, enhanced infiltration of CD4+ T cells and CD4+ forkhead box P3 (FoxP3)+ regulatory T cells (Treg) but reduced numbers of CD8+ T cells. These alterations were further accompanied by transcriptional upregulation of IL4. Thus, TNF and TNFR1 are required in pancreatic ductal carcinoma to ensure optimal CD8+ T cell-mediated immunosurveillance and tumor rejection. Exogenous systemic administration of human TNF, however, which only interacts with murine TNFR1, accelerated tumor progression. This suggests that TNFR1 has basically the capability in the Panc02 model to trigger pro-and anti-tumoral effects but the spatiotemporal availability of TNF seems to determine finally the overall outcome.},
  language  = {en}
}
@article{ZellerMuellerGutberletetal.2013,
  author    = {Zeller, Mario and M{\"u}ller, Alexander and Gutberlet, Marcel and Nichols, Thomas and Hahn, Dietbert and K{\"o}stler, Herbert and Bartsch, Andreas J.},
  title     = {Boosting BOLD fMRI by K-Space Density Weighted Echo Planar Imaging},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0074501},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97233},
  year      = {2013},
  abstract  = {Functional magnetic resonance imaging (fMRI) has become a powerful and influential method to non-invasively study neuronal brain activity. For this purpose, the blood oxygenation level-dependent (BOLD) effect is most widely used. T2* weighted echo planar imaging (EPI) is BOLD sensitive and the prevailing fMRI acquisition technique. Here, we present an alternative to its standard Cartesian recordings, i.e. k-space density weighted EPI, which is expected to increase the signal-to-noise ratio in fMRI data. Based on in vitro and in vivo pilot measurements, we show that fMRI by k-space density weighted EPI is feasible and that this new acquisition technique in fact boosted spatial and temporal SNR as well as the detection of local fMRI activations. Spatial resolution, spatial response function and echo time were identical for density weighted and conventional Cartesian EPI. The signal-to-noise ratio gain of density weighting can improve activation detection and has the potential to further increase the sensitivity of fMRI investigations.},
  language  = {en}
}
@article{RudelMehlitz2013,
  author    = {Rudel, Thomas and Mehlitz, Adrian},
  title     = {Modulation of host signaling and cellular responses by Chlamydia},
  series = {Cell Communication and Signaling},
  journal   = {Cell Communication and Signaling},
  doi       = {10.1186/1478-811X-11-90},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97225},
  year      = {2013},
  abstract  = {Modulation of host cell signaling and cellular functions is key to intracellular survival of pathogenic bacteria. Intracellular growth has several advantages e.g. escape from the humoral immune response and access to a stable nutrient rich environment. Growth in such a preferred niche comes at the price of an ongoing competition between the bacteria and the host as well as other microbes that compete for the very same host resources. This requires specialization and constant evolution of dedicated systems for adhesion, invasion and accommodation. Interestingly, obligate intracellular bacteria of the order Chlamydiales have evolved an impressive degree of control over several important host cell functions. In this review we summarize how Chlamydia controls its host cell with a special focus on signal transduction and cellular modulation.},
  language  = {en}
}
@article{SbieraRonchiLeichetal.2013,
  author    = {Sbiera, Silviu and Ronchi, Cristina L. and Leich, Ellen and Henzel, Katharina and Rosenwald, Andreas and Allolio, Bruno and Fassnacht, Martin},
  title     = {Single Nucleotide Polymorphism Array Profiling of Adrenocortical Tumors - Evidence for an Adenoma Carcinoma Sequence?},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0073959},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97218},
  year      = {2013},
  abstract  = {Adrenocortical tumors consist of benign adenomas and highly malignant carcinomas with a still incompletely understood pathogenesis. A total of 46 adrenocortical tumors (24 adenomas and 22 carcinomas) were investigated aiming to identify novel genes involved in adrenocortical tumorigenesis. High-resolution single nucleotide polymorphism arrays (Affymetrix) were used to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH). Genomic clustering showed good separation between adenomas and carcinomas, with best partition including only chromosome 5, which was highly amplified in 17/22 malignant tumors. The malignant tumors had more relevant genomic aberrations than benign tumors, such as a higher median number of recurrent CNA (2631 vs 94), CNAs >100 Kb (62.5 vs 7) and CN losses (72.5 vs 5.5), and a higher percentage of samples with cnLOH (91\% vs 29\%). Within the carcinoma cohort, a precise genetic pattern (i.e. large gains at chr 5, 7, 12, and 19, and losses at chr 1, 2, 13, 17, and 22) was associated with a better prognosis (overall survival: 72.2 vs 35.4 months, P=0.063). Interestingly, >70\% of gains frequent in beningn were also present in malignant tumors. Notch signaling was the most frequently involved pathway in both tumor entities. Finally, a CN gain at imprinted "IGF2" locus chr 11p15.5 appeared to be an early alteration in a multi-step tumor progression, followed by the loss of one or two alleles, associated with increased IGF2 expression, only in carcinomas. Our study serves as database for the identification of genes and pathways, such as Notch signaling, which could be involved in the pathogenesis of adrenocortical tumors. Using these data, we postulate an adenoma-carcinoma sequence for these tumors.},
  language  = {en}
}
@article{MuellerFiebigWeidaueretal.2013,
  author    = {Mueller, Thomas D. and Fiebig, Juliane E. and Weidauer, Stella E. and Qiu, Li-Yan and Bauer, Markus and Schmieder, Peter and Beerbaum, Monika and Zhang, Jin-Li and Oschkinat, Hartmut and Sebald, Walter},
  title     = {The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed},
  series = {Molecules},
  journal   = {Molecules},
  doi       = {10.3390/molecules181011658},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97196},
  year      = {2013},
  abstract  = {Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop.},
  language  = {en}
}
@article{ShannonHein2013,
  author    = {Shannon, Graver and Hein, Melanie},
  title     = {Tumor cell response to bevacizumab single agent therapy in vitro},
  series = {Cancer Cell International},
  journal   = {Cancer Cell International},
  doi       = {10.1186/1475-2867-13-94},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97185},
  year      = {2013},
  abstract  = {Background Angiogenesis represents a highly multi-factorial and multi-cellular complex (patho-) physiologic event involving endothelial cells, tumor cells in malignant conditions, as well as bone marrow derived cells and stromal cells. One main driver is vascular endothelial growth factor (VEGFA), which is known to interact with endothelial cells as a survival and mitogenic signal. The role of VEGFA on tumor cells and /or tumor stromal cell interaction is less clear. Condition specific (e.g. hypoxia) or tumor specific expression of VEGFA, VEGF receptors and co-receptors on tumor cells has been reported, in addition to the expression on the endothelium. This suggests a potential paracrine/autocrine loop that could affect changes specific to tumor cells. Methods We used the monoclonal antibody against VEGFA, bevacizumab, in various in vitro experiments using cell lines derived from different tumor entities (non small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer (BC) and renal cell carcinoma (RCC)) in order to determine if potential VEGFA signaling could be blocked in tumor cells. The experiments were done under hypoxia, a major inducer of VEGFA and angiogenesis, in an attempt to mimic the physiological tumor condition. Known VEGFA induced endothelial biological responses such as proliferation, migration, survival and gene expression changes were evaluated. Results Our study was able to demonstrate expression of VEGF receptors on tumor cells as well as hypoxia regulated angiogenic gene expression. In addition, there was a cell line specific effect in tumor cells by VEGFA blockade with bevacizumab in terms of proliferation; however overall, there was a limited measurable consequence of bevacizumab therapy detected by migration and survival. Conclusion The present study showed in a variety of in vitro experiments with several tumor cell lines from different tumor origins, that by blocking VEGFA with bevacizumab, there was a limited autocrine or cell-autonomous function of VEGFA signaling in tumor cells, when evaluating VEGFA induced downstream outputs known in endothelial cells.},
  language  = {en}
}
@article{SchultzTerhoeven2013,
  author    = {Schultz, J{\"o}rg and Terhoeven, Niklas},
  title     = {The bilaterian roots of cordon-bleu},
  series = {BMC Research Notes},
  journal   = {BMC Research Notes},
  doi       = {10.1186/1756-0500-6-393},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97161},
  year      = {2013},
  abstract  = {Background The actin cytoskeleton is essential for many physiological processes of eukaryotic cells. The emergence of new actin fibers is initiated by actin nucleators. Whereas most of them are evolutionary old, the cordon-bleu actin nucleator is classified as vertebrate specific. Findings Using sensitive methods for sequence similarity detection, we identified homologs of cordon-bleu not only in non-vertebrate chordates but also in arthropods, molluscs, annelids and platyhelminthes. These genes contain only a single WH2 domain and therefore resemble more the vertebrate cordon-bleu related 1 protein than the three WH2 domain containing cordon-bleu. Furthermore, we identified a homolog of the N-terminal, ubiquitin like, cobl domain of cordon-bleu in the cnidarian Nematostella vectensis. Conclusion Our results suggest that the ur-form of the cordon-bleu protein family evolved already with the emergence of the bilateria by the combination of existing cobl and WH2 domains. Following a vertebrate specific gene-duplication, one copy gained two additional WH2 domains leading to the actin nucleating cordon-bleu. The function of the ur-form of the cordon-bleu protein family is so far unknown. The identification of a homolog in the model organism Drosophila melanogaster could facilitate its experimental characterization.},
  language  = {en}
}
@phdthesis{Schleissinger2013,
  author    = {Schleißinger, Sebastian},
  title     = {Embedding Problems in Loewner Theory},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96782},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {The work at hand studies problems from Loewner theory and is divided into two parts: In part 1 (chapter 2) we present the basic notions of Loewner theory. Here we use a modern form which was developed by F. Bracci, M. Contreras, S. D{\´i}az-Madrigal et al. and which can be applied to certain higher dimensional complex manifolds. We look at two domains in more detail: the Euclidean unit ball and the polydisc. Here we consider two classes of biholomorphic mappings which were introduced by T. Poreda and G. Kohr as generalizations of the class S. We prove a conjecture of G. Kohr about support points of these classes. The proof relies on the observation that the classes describe so called Runge domains, which follows from a result by L. Arosio, F. Bracci and E. F. Wold. Furthermore, we prove a conjecture of G. Kohr about support points of a class of biholomorphic mappings that comes from applying the Roper-Suffridge extension operator to the class S. In part 2 (chapter 3) we consider one special Loewner equation: the chordal multiple-slit equation in the upper half-plane. After describing basic properties of this equation we look at the problem, whether one can choose the coefficient functions in this equation to be constant. D. Prokhorov proved this statement under the assumption that the slits are piecewise analytic. We use a completely different idea to solve the problem in its general form. As the Loewner equation with constant coefficients holds everywhere (and not just almost everywhere), this result generalizes Loewner's original idea to the multiple-slit case. Moreover, we consider the following problems: • The "simple-curve problem" asks which driving functions describe the growth of simple curves (in contrast to curves that touch itself). We discuss necessary and sufficient conditions, generalize a theorem of J. Lind, D. Marshall and S. Rohde to the multiple-slit equation and we give an example of a set of driving functions which generate simple curves because of a certain self-similarity property. • We discuss properties of driving functions that generate slits which enclose a given angle with the real axis. • A theorem by O. Roth gives an explicit description of the reachable set of one point in the radial Loewner equation. We prove the analog for the chordal equation.},
  subject      = {Biholomorphe Abbildung},
  language  = {en}
}
@article{BuchnerBlancoRedondoBunzetal.2013,
  author    = {Buchner, Erich and Blanco Redondo, Beatriz and Bunz, Melanie and Halder, Partho and Sadanandappa, Madhumala K. and M{\"u}hlbauer, Barbara and Erwin, Felix and Hofbauer, Alois and Rodrigues, Veronica and VijayRaghavan, K. and Ramaswami, Mani and Rieger, Dirk and Wegener, Christian and F{\"o}rster, Charlotte},
  title     = {Identification and Structural Characterization of Interneurons of the Drosophila Brain by Monoclonal Antibodies of the W{\"u}rzburg Hybridoma Library},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0075420},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97109},
  year      = {2013},
  abstract  = {Several novel synaptic proteins have been identified by monoclonal antibodies (mAbs) of the W{\"u}rzburg hybridoma library generated against homogenized Drosophila brains, e.g. cysteine string protein, synapse-associated protein of 47 kDa, and Bruchpilot. However, at present no routine technique exists to identify the antigens of mAbs of our library that label only a small number of cells in the brain. Yet these antibodies can be used to reproducibly label and thereby identify these cells by immunohistochemical staining. Here we describe the staining patterns in the Drosophila brain for ten mAbs of the W{\"u}rzburg hybridoma library. Besides revealing the neuroanatomical structure and distribution of ten different sets of cells we compare the staining patterns with those of antibodies against known antigens and GFP expression patterns driven by selected Gal4 lines employing regulatory sequences of neuronal genes. We present examples where our antibodies apparently stain the same cells in different Gal4 lines suggesting that the corresponding regulatory sequences can be exploited by the split-Gal4 technique for transgene expression exclusively in these cells. The detection of Gal4 expression in cells labeled by mAbs may also help in the identification of the antigens recognized by the antibodies which then in addition to their value for neuroanatomy will represent important tools for the characterization of the antigens. Implications and future strategies for the identification of the antigens are discussed.},
  language  = {en}
}
@article{AraragiMlinarBaccinietal.2013,
  author    = {Araragi, Naozumi and Mlinar, Boris and Baccini, Gilda and Gutknecht, Lise and Lesch, Klaus-Peter and Corradetti, Renato},
  title     = {Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis},
  series = {Frontiers in Neuropharmacology},
  journal   = {Frontiers in Neuropharmacology},
  doi       = {10.3389/fphar.2013.00097},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97098},
  year      = {2013},
  abstract  = {Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling.},
  language  = {en}
}
@article{SchusterJohannsenRoewer2013,
  author    = {Schuster, Frank and Johannsen, Stephan and Roewer, Norbert},
  title     = {A Minimal-Invasive Metabolic Test Detects Malignant Hyperthermia Susceptibility in a Patient after Sevoflurane-Induced Metabolic Crisis},
  series = {Case Reports in Anesthesiology},
  journal   = {Case Reports in Anesthesiology},
  doi       = {10.1155/2013/953859},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97080},
  year      = {2013},
  abstract  = {Malignant hyperthermia is a rare but life-threatening complication of general anesthesia in predisposed patients usually triggered by potent inhalation anesthetics and/or the depolarizing muscle relaxant succinylcholine. The authors present a case of delayed sevoflurane-induced malignant hyperthermia in a 21-year-old male patient that was sufficiently treated by discontinuation of trigger agent application and dantrolene infusion. After surviving an MH episode diagnostic procedures are indicated to increase patient safety. In the presented case, the use of a novel minimal-invasive metabolic test with intramuscular injection of halothane and caffeine successfully confirmed MH susceptibility and hence might be an alternative for invasive in vitro contracture testing in selected cases.},
  language  = {en}
}
@article{KaufmannHolzKuebler2013,
  author    = {Kaufmann, Tobias and Holz, Elisa M. and K{\"u}bler, Andrea},
  title     = {Comparison of tactile, auditory, and visual modality for brain-computer interface use: a case study with a patient in the locked-in state},
  series = {Frontiers in Human Neuroscience},
  journal   = {Frontiers in Human Neuroscience},
  doi       = {10.3389/fnins.2013.00129},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97079},
  year      = {2013},
  abstract  = {This paper describes a case study with a patient in the classic locked-in state, who currently has no means of independent communication. Following a user-centered approach, we investigated event-related potentials (ERP) elicited in different modalities for use in brain-computer interface (BCI) systems. Such systems could provide her with an alternative communication channel. To investigate the most viable modality for achieving BCI based communication, classic oddball paradigms (1 rare and 1 frequent stimulus, ratio 1:5) in the visual, auditory and tactile modality were conducted (2 runs per modality). Classifiers were built on one run and tested offline on another run (and vice versa). In these paradigms, the tactile modality was clearly superior to other modalities, displaying high offline accuracy even when classification was performed on single trials only. Consequently, we tested the tactile paradigm online and the patient successfully selected targets without any error. Furthermore, we investigated use of the visual or tactile modality for different BCI systems with more than two selection options. In the visual modality, several BCI paradigms were tested offline. Neither matrix-based nor so-called gaze-independent paradigms constituted a means of control. These results may thus question the gaze-independence of current gaze-independent approaches to BCI. A tactile four-choice BCI resulted in high offline classification accuracies. Yet, online use raised various issues. Although performance was clearly above chance, practical daily life use appeared unlikely when compared to other communication approaches (e.g., partner scanning). Our results emphasize the need for user-centered design in BCI development including identification of the best stimulus modality for a particular user. Finally, the paper discusses feasibility of EEG-based BCI systems for patients in classic locked-in state and compares BCI to other AT solutions that we also tested during the study.},
  language  = {en}
}
@article{HerbertSfaerleaBlumenthal2013,
  author    = {Herbert, Cornelia and Sf{\"a}rlea, Anca and Blumenthal, Terry},
  title     = {Your emotion or mine: labeling feelings alters emotional face perception—an ERP study on automatic and intentional affect labeling},
  series = {Frontiers in Human Neuroscience},
  journal   = {Frontiers in Human Neuroscience},
  doi       = {10.3389/fnhum.2013.00378},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97065},
  year      = {2013},
  abstract  = {Empirical evidence suggests that words are powerful regulators of emotion processing. Although a number of studies have used words as contextual cues for emotion processing, the role of what is being labeled by the words (i.e., one's own emotion as compared to the emotion expressed by the sender) is poorly understood. The present study reports results from two experiments which used ERP methodology to evaluate the impact of emotional faces and self- vs. sender-related emotional pronoun-noun pairs (e.g., my fear vs. his fear) as cues for emotional face processing. The influence of self- and sender-related cues on the processing of fearful, angry and happy faces was investigated in two contexts: an automatic (experiment 1) and intentional affect labeling task (experiment 2), along with control conditions of passive face processing. ERP patterns varied as a function of the label's reference (self vs. sender) and the intentionality of the labeling task (experiment 1 vs. experiment 2). In experiment 1, self-related labels increased the motivational relevance of the emotional faces in the time-window of the EPN component. Processing of sender-related labels improved emotion recognition specifically for fearful faces in the N170 time-window. Spontaneous processing of affective labels modulated later stages of face processing as well. Amplitudes of the late positive potential (LPP) were reduced for fearful, happy, and angry faces relative to the control condition of passive viewing. During intentional regulation (experiment 2) amplitudes of the LPP were enhanced for emotional faces when subjects used the self-related emotion labels to label their own emotion during face processing, and they rated the faces as higher in arousal than the emotional faces that had been presented in the "label sender's emotion" condition or the passive viewing condition. The present results argue in favor of a differentiated view of language-as-context for emotion processing.},
  language  = {en}
}
@article{KleinschnitzMenclGarzetal.2013,
  author    = {Kleinschnitz, Christoph and Mencl, Stine and Garz, Cornelia and Niklass, Solveig and Braun, Holger and G{\"o}b, Eva and Homola, Gy{\"o}rgy and Heinze, Hans-Jochen and Reymann, Klaus G. and Schreiber, Stefanie},
  title     = {Early microvascular dysfunction in cerebral small vessel disease is not detectable on 3.0 Tesla magnetic resonance imaging: a longitudinal study in spontaneously hypertensive stroke-prone rats},
  series = {Experimental \& Translational Stroke Medicine},
  journal   = {Experimental \& Translational Stroke Medicine},
  doi       = {10.1186/2040-7378-5-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97056},
  year      = {2013},
  abstract  = {Background Human cerebral small vessel disease (CSVD) has distinct histopathologic and imaging findings in its advanced stages. In spontaneously hypertensive stroke-prone rats (SHRSP), a well-established animal model of CSVD, we recently demonstrated that cerebral microangiopathy is initiated by early microvascular dysfunction leading to the breakdown of the blood-brain barrier and an activated coagulatory state resulting in capillary and arteriolar erythrocyte accumulations (stases). In the present study, we investigated whether initial microvascular dysfunction and other stages of the pathologic CSVD cascade can be detected by serial magnetic resonance imaging (MRI). Findings Fourteen SHRSP and three control (Wistar) rats (aged 26-44 weeks) were investigated biweekly by 3.0 Tesla (3 T) MRI. After perfusion, brains were stained with hematoxylin-eosin and histology was correlated with MRI data. Three SHRSP developed terminal CSVD stages including cortical, hippocampal, and striatal infarcts and macrohemorrhages, which could be detected consistently by MRI. Corresponding histology showed small vessel thromboses and increased numbers of small perivascular bleeds in the infarcted areas. However, 3 T MRI failed to visualize intravascular erythrocyte accumulations, even in those brain regions with the highest densities of affected vessels and the largest vessels affected by stases, as well as failing to detect small perivascular bleeds. Conclusion Serial MRI at a field strength of 3 T failed to detect the initial microvascular dysfunction and subsequent small perivascular bleeds in SHRSP; only terminal stages of cerebral microangiopathy were reliably detected. Further investigations at higher magnetic field strengths (7 T) using blood- and flow-sensitive sequences are currently underway.},
  language  = {en}
}
@article{SchultzKeller2013,
  author    = {Schultz, J{\"o}rg and Keller, Daniela Barbara},
  title     = {Connectivity, Not Frequency, Determines the Fate of a Morpheme},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0069945},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97039},
  year      = {2013},
  abstract  = {Morphemes are the smallest meaningful parts of words and therefore represent a natural unit to study the evolution of words. To analyze the influence of language change on morphemes, we performed a large scale analysis of German and English vocabulary covering the last 200 years. Using a network approach from bioinformatics, we examined the historical dynamics of morphemes, the fixation of new morphemes and the emergence of words containing existing morphemes. We found that these processes are driven mainly by the number of different direct neighbors of a morpheme in words (connectivity, an equivalent to family size or type frequency) and not its frequency of usage (equivalent to token frequency). This contrasts words, whose survival is determined by their frequency of usage. We therefore identified features of morphemes which are not dictated by the statistical properties of words. As morphemes are also relevant for the mental representation of words, this result might enable establishing a link between an individual's perception of language and historical language change.},
  language  = {en}
}
@article{DandekarLiangKrueger2013,
  author    = {Dandekar, Thomas and Liang, Chunguang and Kr{\"u}ger, Beate},
  title     = {GoSynthetic database tool to analyse natural and engineered molecular processes},
  series = {Database},
  journal   = {Database},
  doi       = {10.1093/database/bat043},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97023},
  year      = {2013},
  abstract  = {An essential topic for synthetic biologists is to understand the structure and function of biological processes and involved proteins and plan experiments accordingly. Remarkable progress has been made in recent years towards this goal. However, efforts to collect and present all information on processes and functions are still cumbersome. The database tool GoSynthetic provides a new, simple and fast way to analyse biological processes applying a hierarchical database. Four different search modes are implemented. Furthermore, protein interaction data, cross-links to organism-specific databases (17 organisms including six model organisms and their interactions), COG/KOG, GO and IntAct are warehoused. The built in connection to technical and engineering terms enables a simple switching between biological concepts and concepts from engineering, electronics and synthetic biology. The current version of GoSynthetic covers more than one million processes, proteins, COGs and GOs. It is illustrated by various application examples probing process differences and designing modifications.},
  language  = {en}
}
@article{ReichertSchmalzlPrageretal.2013,
  author    = {Reichert, Johannes and Schmalzl, Jonas and Prager, Patrick and Gilbert, Fabian and Quent, Verena M. C. and Steinert, Andre F. and Rudert, Maximilian and N{\"o}th, Ulrich},
  title     = {Synergistic effect of Indian hedgehog and bone morphogenetic protein-2 gene transfer to increase the osteogenic potential of human mesenchymal stem cells},
  series = {Stem Cell Research \& Therapy},
  journal   = {Stem Cell Research \& Therapy},
  doi       = {10.1186/scrt316},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97010},
  year      = {2013},
  abstract  = {Introduction To stimulate healing of large bone defects research has concentrated on the application of mesenchymal stem cells (MSCs). Methods In the present study, we induced the overexpression of the growth factors bone morphogenetic protein 2 (BMP-2) and/or Indian hedgehog (IHH) in human MSCs by adenoviral transduction to increase their osteogenic potential. GFP and nontransduced MSCs served as controls. The influence of the respective genetic modification on cell metabolic activity, proliferation, alkaline phosphatase (ALP) activity, mineralization in cell culture, and osteogenic marker gene expression was investigated. Results Transduction had no negative influence on cell metabolic activity or proliferation. ALP activity showed a typical rise-and-fall pattern with a maximal activity at day 14 and 21 after osteogenic induction. Enzyme activity was significantly higher in groups cultured with osteogenic media. The overexpression of BMP-2 and especially IHH + BMP-2 resulted in a significantly higher mineralization after 28 days. This was in line with obtained quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analyses, which showed a significant increase in osteopontin and osteocalcin expression for osteogenically induced BMP-2 and IHH + BMP-2 transduced cells when compared with the other groups. Moreover, an increase in runx2 expression was observed in all osteogenic groups toward day 21. It was again more pronounced for BMP-2 and IHH + BMP-2 transduced cells cultured in osteogenic media. Conclusions In summary, viral transduction did not negatively influence cell metabolic activity and proliferation. The overexpression of BMP-2 in combination with or without IHH resulted in an increased deposition of mineralized extracellular matrix, and expression of osteogenic marker genes. Viral transduction therefore represents a promising means to increase the osteogenic potential of MSCs and the combination of different transgenes may result in synergistic effects.},
  language  = {en}
}
@article{LoehrMolcanyiPoggenborgetal.2013,
  author    = {L{\"o}hr, Mario and Molcanyi, Marek and Poggenborg, J{\"o}rg and Spuentrup, Elmar and Runge, Matthias and R{\"o}hn, Gabriele and H{\"a}rtig, Wolfgang and Hescheler, J{\"u}rgen and Hampl, J{\"u}rgen A.},
  title     = {Intracerebral Administration of Heat-Inactivated Staphylococcus Epidermidis Enhances Oncolysis and Prolongs Survival in a 9L Orthotopic Gliosarcoma Model},
  series = {Cellular Physiology and Biochemistry},
  journal   = {Cellular Physiology and Biochemistry},
  doi       = {10.1159/000350081},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96754},
  year      = {2013},
  abstract  = {Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Na{\"i}ve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.},
  language  = {en}
}
@article{EyrichRachorSchreiberetal.2013,
  author    = {Eyrich, Matthias and Rachor, Johannes and Schreiber, Susanne C. and W{\"o}lfl, Matthias and Schlegel, Paul G.},
  title     = {Dendritic cell vaccination in pediatric gliomas: lessons learnt and future perspectives},
  series = {Frontiers in Pediatrics},
  journal   = {Frontiers in Pediatrics},
  doi       = {10.3389/fped.2013.00012},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96937},
  year      = {2013},
  abstract  = {Immunotherapy of malignant gliomas with autologous dendritic cells (DCs) in addition to surgery and radiochemotherapy has been a focus of intense research during the past decade. Since both children and adults are affected by this highly aggressive brain tumor, 10-15\% of the several hundred vaccinated patients represent children, making pediatric glioma patients the largest uniform pediatric vaccination cohort so far. In general, DC vaccination in malignant gliomas has been shown to be safe and several studies with a non-vaccinated control group could clearly demonstrate a survival benefit for the vaccinated patients. Interestingly, children and adolescents below 21 years of age seem to benefit even more than adult patients. This review summarizes the findings of the 25 clinical trials published so far and gives a perspective how DC vaccination could be implemented as part of multimodal therapeutic strategies in the near future.},
  language  = {en}
}
@article{GaubatzEsterlechnerReichertetal.2013,
  author    = {Gaubatz, Stefan and Esterlechner, Jasmina and Reichert, Nina and Iltzsche, Fabian and Krause, Michael and Finkernagel, Florian},
  title     = {LIN9, a Subunit of the DREAM Complex, Regulates Mitotic Gene Expression and Proliferation of Embryonic Stem Cells},
  series = {PLoS ONE},
  journal   = {PLoS ONE},
  doi       = {10.1371/journal.pone.0062882},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96922},
  year      = {2013},
  abstract  = {The DREAM complex plays an important role in regulation of gene expression during the cell cycle. We have previously shown that the DREAM subunit LIN9 is required for early embryonic development and for the maintenance of the inner cell mass in vitro. In this study we examined the effect of knocking down LIN9 on ESCs. We demonstrate that depletion of LIN9 alters the cell cycle distribution of ESCs and results in an accumulation of cells in G2 and M and in an increase of polyploid cells. Genome-wide expression studies showed that the depletion of LIN9 results in downregulation of mitotic genes and in upregulation of differentiation-specific genes. ChIP-on chip experiments showed that mitotic genes are direct targets of LIN9 while lineage specific markers are regulated indirectly. Importantly, depletion of LIN9 does not alter the expression of pluripotency markers SOX2, OCT4 and Nanog and LIN9 depleted ESCs retain alkaline phosphatase activity. We conclude that LIN9 is essential for proliferation and genome stability of ESCs by activating genes with important functions in mitosis and cytokinesis.},
  language  = {en}
}