@phdthesis{Pasch2016,
  author    = {Pasch, Elisabeth},
  title     = {The role of SUN4 and related proteins in sperm head formation and fertility},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139092},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Spermiogenesis describes the differentiation of haploid germ cells into motile, fertilization-competent spermatozoa. During this fundamental transition the species-specific sperm head is formed, which necessitates profound nuclear restructuring coincident with the assembly of sperm-specific structures and chromatin compaction. In the case of the mouse, it is characterized by reshaping of the early round spermatid nucleus into an elongated sickle-shaped sperm head. This tremendous shape change requires the transduction of cytoskeletal forces onto the nuclear envelope (NE) or even further into the nuclear interior. LINC (linkers of nucleoskeleton and cytoskeleton) complexes might be involved in this process, due to their general function in bridging the NE and thereby physically connecting the nucleus to the peripheral cytoskeleton. LINC complexes consist of inner nuclear membrane integral SUN-domain proteins and outer nuclear membrane KASH-domain counterparts. SUN- and KASH-domain proteins are directly connected to each other within the perinuclear space, and are thus capable of transferring forces across the NE. To date, these protein complexes are known for their essential functions in nuclear migration, anchoring and positioning of the nucleus, and even for chromosome movements and the maintenance of cell polarity and nuclear shape. In this study LINC complexes were investigated with regard to their potential role in sperm head formation, in order to gain further insight into the processes occurring during spermiogenesis. To this end, the behavior and function of the testis-specific SUN4 protein was studied. The SUN-domain protein SUN4, which had received limited characterization prior to this work, was found to be exclusively expressed in haploid stages during germ cell development. In these cell stages, it specifically localized to the posterior NE at regions decorated by the manchette, a spermatid-specific structure which was previously shown to be involved in nuclear shaping. Mice deficient for SUN4 exhibited severely disorganized manchette residues and gravely misshapen sperm heads. These defects resulted in a globozoospermia-like phenotype and male mice infertility. Therefore, SUN4 was not only found to be mandatory for the correct assembly and anchorage of the manchette, but also for the correct localization of SUN3 and Nesprin1, as well as of other NE components. Interaction studies revealed that SUN4 had the potential to interact with SUN3, Nesprin1, and itself, and as such is likely to build functional LINC complexes that anchor the manchette and transfer cytoskeletal forces onto the nucleus. Taken together, the severe impact of SUN4 deficiency on the nucleocytoplasmic junction during sperm development provided direct evidence for a crucial role of SUN4 and other LINC complex components in mammalian sperm head formation and fertility.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{LuiblneeHermann2014,
  author    = {Luibl [n{\´e}e Hermann], Christiane},
  title     = {The role of the neuropeptides NPF, sNPF, ITP and PDF in the circadian clock of Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-93796},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Organisms have evolved endogenous clocks which allow them to organize their behavior, metabolism and physiology according to the periodically changing environmental conditions on earth. Biological rhythms that are synchronized to daily changes in environment are governed by the so-called circadian clock. Since decades, chronobiologists have been investigating circadian clocks in various model organisms including the fruitfly Drosophila melanogaster, which was used in the present thesis. Anatomically, the circadian clock of the fruitfly consists of about 150 neurons in the lateral and dorsal protocerebrum, which are characterized by their position, morphology and neurochemistry. Some of these neurons had been previously shown to contain either one or several neuropeptides, which are thought to be the main signaling molecules used by the clock. The best investigated of these neuropeptides is the Pigment Dispersing Factor (PDF), which had been shown to constitute a synchronizing signal between clock neurons as well as an output factor of the clock. In collaboration with various coworkers, I investigated the roles of three other clock expressed neuropeptides for the generation of behavioral rhythms and the partly published, partly unpublished data are presented in this thesis. Thereby, I focused on the Neuropeptide F (NPF), short Neuropeptide F (sNPF) and the Ion Transport Peptide (ITP). We show that part of the neuropeptide composition within the clock network seems to be conserved among different Drosophila species. However, the PDF expression pattern in certain neurons varied in species deriving from lower latitudes compared to higher latitudes. Together with findings on the behavioral level provided by other people, these data suggest that different species may have altered certain properties of their clocks - like the neuropeptide expression in certain neurons - in order to adapt their behavior to different habitats. We then investigated locomotor rhythms in Drosophila melanogaster flies, in which neuropeptide circuits were genetically manipulated either by cell ablation or RNA interference (RNAi). We found that none of the investigated neuropeptides seems to be of equal importance for circadian locomotor rhythms as PDF. PDF had been previously shown to be necessary for rhythm maintenance in constant darkness (DD) as well as for the generation of morning (M) activity and for the right phasing of the evening (E) activity in entrained conditions. We now demonstrate that NPF and ITP seem to promote E activity in entrained conditions, but are clearly not the only factors doing so. In addition, ITP seems to reduce nighttime activity. Further, ITP and possibly also sNPF constitute weak period shortening components in DD, thereby opposing the effect of PDF. However, neither NPF or ITP, nor sNPF seem to be necessary in the clock neurons for maintaining rhythmicity in DD. It had been previously suggested that PDF is released rhythmically from the dorsal projection terminals. Now we discovered a rhythm in ITP immunostaining in the dorsal projection terminals of the ITP+ clock neurons in LD, suggesting a rhythm in peptide release also in the case of ITP. Rhythmic release of both ITP and PDF seems to be important to maintain rhythmic behavior in DD, since constantly high levels of PDF and ITP in the dorsal protocerebrum lead to behavioral arrhythmicity. Applying live-imaging techniques we further demonstrate that sNPF acts in an inhibitory way on few clock neurons, including some that are also activated by PDF, suggesting that it acts as signaling molecule within the clock network and has opposing effects to PDF. NPF did only evoke very little inhibitory responses in very few clock neurons, suggesting that it might rather be used as a clock output factor. We were not able to apply the same live-imaging approach for the investigation of the clock neuron responsiveness to ITP, but overexpression of ITP with various driver lines showed that the peptide most likely acts mainly in clock output pathways rather than inter-clock neuron communication. Taking together, I conclude that all investigated peptides contribute to the control of locomotor rhythms in the fruitfly Drosophila melanogaster. However, this control is in most aspects dominated by the actions of PDF and rather only fine-tuned or complemented by the other peptides. I assume that there is a high complexity in spatial and temporal action of the different neuropeptides in order to ensure correct signal processing within the clock network as well as clock output.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Blaettner2016,
  author    = {Bl{\"a}ttner, Sebastian},
  title     = {The role of the non-ribosomal peptide synthetase AusAB and its product phevalin in intracellular virulence of Staphylococcus aureus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146662},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Staphylococcus aureus is a prevalent commensal bacterium which represents one of the leading causes in health care-associated bacterial infections worldwide and can cause a variety of different diseases ranging from simple abscesses to severe and life threatening infections including pneumonia, osteomyelitis and sepsis. In recent times multi-resistant strains have emerged, causing severe problems in nosocomial as well as community-acquired (CA) infection settings, especially in the United States (USA). Therefore S. aureus has been termed as a superbug by the WHO, underlining the severe health risk originating from it. Today, infections in the USA are dominated by S. aureus genotypes which are classified as USA300 and USA400, respectively. Strains of genotype USA300 are responsible for about 70\% of the CA infections. The molecular mechanisms which render S. aureus such an effective pathogen are still not understood in its entirety. For decades S. aureus was thought to be a strictly extracellular pathogen relying on pore-forming toxins like α-hemolysin to damage human cells and tissue. Only recently it has been shown that S. aureus can enter non-professional phagocytes, using adhesins like the fibronectin-binding proteins which mediate an endocytotic uptake into the host cells. The bacteria are consequently localized to endosomes, where the degradation of enclosed bacterial cells through phagosome maturation would eventually occur. S. aureus can avoid degradation, and translocate to the cellular cytoplasm, where it can replicate. The ability to cause this so-called phagosomal escape has mainly been attributed to a family of amphiphilic peptides called phenol soluble modulins (PSMs), but as studies have shown, they are not sufficient. In this work I used a transposon mutant library in combination with automated fluorescence microscopy to screen for genes involved in the phagosomal escape process and intracellular survival of S. aureus. I thereby identified a number of genes, including a non-ribosomal peptide synthetase (NRPS). The NRPS, encoded by the genes ausA and ausB, produces two types of small peptides, phevalin and tyrvalin. Mutations in the ausAB genes lead to a drastic decrease in phagosomal escape rates in epithelial cells, which were readily restored by genetic complementation in trans as well as by supplementation of synthetic phevalin. In leukocytes, phevalin interferes with calcium fluxes and activation of neutrophils and promotes cytotoxicity of intracellular bacteria in both, macrophages and neutrophils. Further ausAB is involved in survival and virulence of the bacterium during mouse lung pneumoniae. The here presented data demonstrates the contribution of the bacterial cyclic dipeptide phevalin to S. aureus virulence and suggests, that phevalin directly acts on a host cell target to promote cytotoxicity of intracellular bacteria.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Chan2002,
  author    = {Chan, Gordon},
  title     = {The Role of Vav-1, Vav-2 and Lsc in NK T cell development and NK cell cytotoxicity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3645},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {The hematopoietic-specific Rho-family GTP exchange factor (GEF) Vav-1 is a regulator of lymphocyte antigen receptor signaling and mediates normal maturation and activation of B and T cells. Recent findings suggest that Vav-1 also forms part of signaling pathways required for natural and antibody dependent cellular cytotoxicity (ADCC) of human NK cells. In this study, I show that Vav-1 is also expressed in murine NK cells. Vav-1-/- mice had normal numbers of splenic NK cells, and these displayed a similar expression profile of NK cell receptors as cells from wild type mice. Unexpectedly, IL-2-activated Vav-1-/- NK cells retained normal ADCC. Fc-receptor mediated activation of ERK, JNK, and p38 was also normal. In contrast, Vav-1-/- NK cells exhibited reduced natural cytotoxicity against EL4, C4.4.25, RMA and RMA/S. Together, these results demonstrate that Vav-1 is dispensable for mainstream NK cell development, but is required for NK cell natural cytotoxicity. Vav-2, a protein homologous to Vav-1 has also been implicated in NK cell functions. However, NK cells from Vav-2-/- mice have normal cytotoxic activities and NK cells that lack both Vav-1 and Vav-2 exhibit similar defect as Vav-1-/- cells. Thus Vav-2 has no apparent function in the development and the activation of NK cells. Although NK cell development is normal in Vav-1-/- mice, their numbers of NKT cells were dramatically diminished. Furthermore, NKT cells from Vav-1 mutant mice failed to produce IL-4 and IFNg following in vivo CD3 stimulation. A similar loss of NKT cells was observed in Vav-1-/-Vav-2-/- mice, but not in Vav-2-/- mice, suggesting that only Vav-1, and not Vav-2, is an essential regulator of NKT cell development and NK cell cytotoxicity. Similar to Vav-1, Lsc is a Rho GEF that is expressed specifically in the hematopoietic system. It contains a regulator of G-protein signaling (RGS) domain which negatively regulates the Ga12 and Ga13 subunits of G-protein coupled receptors (GPCRs). This study shows that NK and NKT cell development are normal in Lsc-/- mice. However, NK cells from mutant mice display enhanced cytotoxic responses towards a panel of tumor cells. These data implicate for the first time a RGS-containing Rho GEF in cytotoxic responses and suggest that Lsc down-modulate NK cell activation.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{Schindelin2005,
  author    = {Schindelin, Johannes},
  title     = {The standard brain of Drosophila melanogaster and its automatic segmentation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-15518},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {In this thesis, I introduce the Virtual Brain Protocol, which facilitates applications of the Standard Brain of Drosophila melanogaster. By providing reliable and extensible tools for the handling of neuroanatomical data, this protocol simplifies and organizes the recurring tasks involved in these applications. It is demonstrated that this protocol can also be used to generate average brains, i.e. to combine recordings of several brains with the same features such that the common features are emphasized. One of the most important steps of the Virtual Insect Protocol is the aligning of newly recorded data sets with the Standard Brain. After presenting methods commonly applied in a biological or medical context to align two different recordings, it is evaluated to what extent this alignment can be automated. To that end, existing Image Processing techniques are assessed. I demonstrate that these techniques do not satisfy the requirements needed to guarantee sensible alignments between two brains. Then, I analyze what needs to be taken into account in order to formulate an algorithm which satisfies the needs of the protocol. In the last chapter, I derive such an algorithm using methods from Information Theory, which bases the technique on a solid mathematical foundation. I show how Bayesian Inference can be applied to enhance the results further. It is demonstrated that this approach yields good results on very noisy images, detecting apparent boundaries between structures. The same approach can be extended to take additional knowledge into account, e.g. the relative position of the anatomical structures and their shape. It is shown how this extension can be utilized to segment a newly recorded brain automatically.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Hein2004,
  author    = {Hein, Silke},
  title     = {The survival of grasshoppers and bush crickets in habitats variable in space and time},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-9140},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Die zunehmende Nutzung von Landschaften f{\"u}hrt zu einer steigenden Fragmentierung sch{\"u}tzenswerter Fl{\"a}chen. Damit verbunden ist eine Zerschneidung von großen Populationen in Metapopulationen. In solchen F{\"a}llen bestimmt das Gleichgewicht zwischen Aussterben und Besiedlung von Habitaten die regionale {\"U}berlebenswahrscheinlichkeit von Arten. Um diese bestimmen, braucht man ein gutes Verst{\"a}ndnis der Habitatanspr{\"u}che der Arten, sowie Informationen {\"u}ber ihr Ausbreitungsverhalten. Ziel dieser Arbeit war es, geeignete Fl{\"a}chen f{\"u}r Heuschrecken in einer Landschaft identifizieren zu k{\"o}nnen, sowie einen Beitrag zur Quantifizierung der Erreichbarkeit einzelner Fl{\"a}chen durch Individuen zu leisten. Der erste Teil dieser Arbeit besch{\"a}ftigt sich mit der Quantifizierung der Habitateignung von Fl{\"a}chen f{\"u}r Heuschrecken. Dazu habe ich statistische Habitateignungsmodelle mittels logistischer Regression erstellt, evaluiert und validiert. Es zeigte sich, dass die Habitatwahl der Heuschrecken auf einer mittleren r{\"a}umlichen Skalenebene erfolgt. Dies steht mit der beobachteten Ausbreitungsdistanz der Tiere im Einklang. Neben dem nur grob klassifizierten Landschaftsfaktor „Biotoptyp" korrelieren vor allem strukturelle Faktoren sowie abiotische Faktoren mit dem Vorkommen der Heuschreckenarten. Bei der Bestimmung eines gemeinsamen Models f{\"u}r alle drei Heuschreckenarten erwies sich das Model der Art S. lineatus mit den Parametern Biotoptyp und Vegetationsh{\"o}he als am besten geeignet zur Vorhersage der Vorkommen der anderen Heuschreckenarten. Um zu testen, ob auch die Vorkommen von Arten unterschiedlicher Tiergruppen mittels eines gemeinsamen Modells vorhergesagt werden k{\"o}nnen, habe ich sowohl die Heuschreckenmodelle zur Prognose von Faltervorkommen getestet, als auch Modelle f{\"u}r Falter auf Heuschrecken {\"u}bertragen. Dabei erwiesen sich die Heuschreckenmodelle zur Prognose der anderen Arten weniger geeignet als das Modell f{\"u}r das Widderchen Z. carniolica in das der Anteil an geeignetem Habitat sowie die Vorkommen der beiden Saugpflanzen C. jacea und S. columbaria einfließen. Diese Art wird als standorttreu eingestuft und repr{\"a}sentiert damit auch die anderen Arten, die typisch f{\"u}r S{\"a}ume und Halbtrockenrasen sind. Die erh{\"o}hte Mobilit{\"a}t von Z. carniolica im Vergleich zu den Heuschrecken garantiert gleichzeitig auch die Erreichbarkeit aller geeigneten Fl{\"a}chen im Gebiet und damit ein Modell, das nur unwesentlich durch Zufallseffekte bei der Besiedlung beeinflusst wird. Neben der Habitatqualit{\"a}t/-quantit{\"a}t spielt vor allem der Austausch zwischen Fl{\"a}chen eine entscheidende Rolle f{\"u}r das {\"U}berleben der Metapopulation. Im zweiten Teil meiner Arbeit habe ich mich sowohl theoretisch als auch empirisch, mit dem Ausbreitungsverhalten von Heuschrecken besch{\"a}ftigt. In Freilandexperimenten konnte ich zeigen, dass die Annahme eines dichotomen Bewegungsverhaltens f{\"u}r Heuschrecken in einer realen Landschaft nicht zutrifft. Vielmehr wird die Bewegung in einer Fl{\"a}che besser als Kontinuum beschrieben das durch strukturelle Resistenz, Temperatur, Mortalit{\"a}tsrisiko und Ressourcenverf{\"u}gbarkeit bestimmt wird. Die jeweilige Kombination dieser Parameter veranlasst die Tiere dann zu einem entsprechenden Bewegungsmuster, das sich zwischen den beiden Extremen gerichteter und zuf{\"a}lliger Lauf bewegt. In Experimenten zum Grenzverhalten von Heuschrecken best{\"a}tigte sich dieses Ergebnis. F{\"u}r verschiedene Grenzstrukturen konnte ich unterschiedliche {\"U}bertrittswahrscheinlichkeiten nachweisen. Weiterhin konnte ich feststellen, dass Heuschrecken geeignete Habitate aus einer gewissen Entfernung detektieren k{\"o}nnen. Da das Ausbreitungsverhalten von Tieren in theoretischen Modellen eine wichtige Rolle spielt, k{\"o}nnen diese empirischen Daten zur Parametrisierung dieser Modelle verwendet werden. Zus{\"a}tzlich zum Einfluss des Laufmusters der Tiere auf die Erreichbarkeit geeigneter Habitate, zeigte sich in den von mir durchgef{\"u}hrten Simulationsstudien deutlich, dass der landschaftliche Kontext, in dem die Ausbreitung stattfindet, die Erreichbarkeit einzelner Habitate beeinflusst. Dieser Effekt ist zus{\"a}tzlich abh{\"a}ngig von der Mortalit{\"a}tsrate beim Ausbreitungsvorgang. Mit den Ergebnissen aus den Untersuchungen zur Habitateignung lassen sich die f{\"u}r Heuschrecken geeigneten Habitate in einer Landschaft identifizieren. Somit l{\"a}sst sich die potentielle Eignung einer Fl{\"a}che als Habitat, basierend auf Vorhersagen {\"u}ber die {\"A}nderung des Biotoptyps durch ein Managementverfahren, vorhersagen. Diese Information allein reicht aber nicht aus, um die regionale {\"U}berlebenswahrscheinlichkeit einer Art bestimmen zu k{\"o}nnen. Meine Untersuchungen zum Ausbreitungsverhalten zeigen deutlich, dass die Erreichbarkeit geeigneter Fl{\"a}chen von der r{\"a}umlichen Anordnung der Habitate und der Struktur der Fl{\"a}chen, die zwischen Habitaten liegen, abh{\"a}ngt. Zus{\"a}tzlich spielen individuenspezifische Faktoren wie Motivation und physiologische Faktoren eine ausschlaggebende Rolle f{\"u}r die Erreichbarkeit von geeigneten Fl{\"a}chen.},
  subject      = {Naturschutzgebiet Hohe Wann},
  language  = {en}
}
@phdthesis{Pusch2015,
  author    = {Pusch, Tobias},
  title     = {The transcription factor NFATc1 mediates cytotoxic T cell function in vitro and in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123690},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {While numerous experiments on NFAT were already performed with CD4+ T cells showing defective cytokine release and a reduced T helper cell development, no detailed studies existed for CD8+ T cells. From this point, we wanted to examine the impact of NFATc1 and c2 on the physiological functions of CD8+ T cells in vitro and in vivo. Therefore, we used a murine infection model with the bacteria Listeria monocytogenes and mice in which NFATc1 was specifically depleted in the T cell compartment. Our first in vitro studies showed a typical NFATc1 and c2 nuclear translocation and changes on mRNA levels upon T cell activation similarly in CD4+ as well as in CD8+ T cells extracted from wild type mice. NFAT nuclear translocation is important for target gene activation and generation of effector functions. Stimulated T cell populations lacking NFATc1 and/or NFATc2 showed a markedly decreased expression of Th1/Tc1 cytokines, as e.g. IL 2 and IFNγ being important for the clearance of intracellular pathogens. From our in vitro model for the generation of allogenically reactive cytotoxic CD8+ T cells, we revealed a decreased killing and lytic granule-release capacity in Nfatc1 inactivated CD8+ T cells whereas NFATc2-/- cytotoxic T cells did not show an altered cytotoxic response compared to wild type cells. Interestingly, we found lytic granules accumulated and mitochondria not getting translocated to the immunological synapse upon re-stimulation in NFATc1-deficient CD8+ T cells. Together with results showing the CsA insensitivity of the CTL killing/degranulation capacities, we assume that some major cellular processes are affected by NFATc1 which are not directly linked to the TCR-induced signal transduction cascade. We also showed the importance of NFATc1 in T cells during intracellular infections with the bacteria Listeria monocytogenes in an in vivo mouse model. After five days, only few bacteria were detected in wt mice whereas high amounts of Listeria particles were extracted from livers of Nfatc1fl/fl x Cd4 cre mice. Although the reactivity towards the pathogen was similar in both groups, a decreased cytokine expression in NFATc1-/- CD8+ T cells was observed together with an altered memory cell generation. Our results show the importance of NFATc1 in CD8+ T cells and give some clue for a possible connection to other basal cellular functions, as e.g. the formation of an immunological synapse.},
  subject      = {Transkriptionsfaktor},
  language  = {en}
}
@phdthesis{Spohn1999,
  author    = {Spohn, Gunther},
  title     = {The transcriptional control of virulence gene expression in Helicobacter pylori},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-2334},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1999},
  abstract  = {The Gram-negative, spiral-shaped, microaerophilic bacterium Helicobacter pylori is the causative agent of various disorders of the upper gastrointestinal tract, such as chronic superficial gastritis, chronic active gastritis, peptic ulceration and adenocarcinoma. Although many of the bacterial factors associated with disease development have been analysed in some detail in the recent years, very few studies have focused so far on the mechanisms that regulate expression of these factors at the molecular level. In an attempt to obtain an overview of the basic mechanisms of virulence gene expression in H. pylori, three important virulence factors of this pathogen, representative of different pathogenic mechanisms and different phases of the infectious process, are investigated in detail in the present thesis regarding their transcriptional regulation. As an essential factor for the early phase of infection, including the colonisation of the gastric mucosa, the flagella are analysed; the chaperones including the putative adhesion factors GroEL and DnaK are investigated as representatives of the phase of adherence to the gastric epithelium and persistence in the mucus layer; and finally the cytotoxin associated antigen CagA is analysed as representative of the cag pathogenicity island, which is supposed to account for the phenomena of chronic inflammation and tissue damage observed in the later phases of infection. RNA analyses and in vitro transcription demonstrate that a single promoter regulates expression of cagA, while two promoters are responsible for expression of the upstream divergently transcribed cagB gene. All three promoters are shown to be recognised by RNA polymerase containing the vegetative sigma factor sigma 80. Promoter deletion analyses establish that full activation of the cagA promoter requires sequences up to -70 and binding of the C-terminal portion of the alpha subunit of RNA polymerase to an UP-like element located between -40 and -60, while full activation of the major cagB promoter requires sequences upstream of -96 which overlap with the cagA promoter. These data suggest that the promoters of the pathogenicity island represent a class of minimum promoters, that ensure a basic level of transcription, while full activation requires regulatory elements or structural DNA binding proteins that provide a suitable DNA context. Regarding flagellar biosynthesis, a master transcriptional factor is identified that regulates expression of a series of flagellar basal body and hook genes in concert with the alternative sigma factor sigma 54. Evidence is provided that this regulator, designated FlgR (for flagellar regulatory protein), is necessary for motility and transcription of five promoters for seven basal body and hook genes. In addition, FlgR is shown to act as a repressor of transcription of the sigma 28-regulated promoter of the flaA gene, while changes in DNA topology are shown to affect transcription of the sigma 54-regulated flaB promoter. These data indicate that the regulatory network that governs flagellar gene expression in H. pylori shows similarities to the systems of both Salmonella spp. and Caulobacter crescentus. In contrast to the flagellar genes which are regulated by three different sigma factors, the three operons encoding the major chaperones of H. pylori are shown to be transcribed by RNA polymerase containing the vegetative sigma factor sigma 80. Expression of these operons is shown to be regulated negatively by the transcriptional repressor HspR, a homologue of a repressor protein of Streptomyces spp., known to be involved in negative regulation of heat shock genes. In vitro studies with purified recombinant HspR establish that the protein represses transcription by binding to large DNA regions centered around the transcription initiation site in the case of one promoter, and around -85 and -120 in the case of the the other two promoters. In contrast to the situation in Streptomyces, where transcription of HspR-regulated genes is induced in response to heat shock, transcription of the HspR-dependent genes in H. pylori is not inducible with thermal stimuli. Transcription of two of the three chaperone encoding operons is induced by osmotic shock, while transcription of the third operon, although HspR-dependent, is not affected by salt treatment. Taken together, the analyses carried out indicate that H. pylori has reduced its repertoire of specific regulatory proteins to a basic level that may ensure coordinate regulation of those factors that are necessary during the initial phase of infection including the passage through the gastric lumen and the colonisation of the gastric mucosa. The importance of DNA topology and/or context for transcription of many virulence gene promoters may on the other hand indicate, that a sophisticated global regulatory network is present in H. pylori, which influences transcription of specific subsets of virulence genes in response to changes in the microenvironment.},
  subject      = {Helicobacter-pylori-Infektion},
  language  = {en}
}
@phdthesis{Jenett2007,
  author    = {Jenett, Arnim},
  title     = {The Virtual Insect Brain Protocol : development and application of software for the standardization of neuroanatomy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22297},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Since the fruit fly Drosophila melanogaster entered the laboratories as a model organism, new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain rapidly accumulated. Nowadays this concerted assault obtains its main thrust form Gal4 expression patterns that can be visualized and provide the means for manipulating -in unrestrained animals- groups of neurons of the brain. To take advantage of these patterns one needs to know their anatomy. This thesis describes the Virtual Insect Brain (VIB) protocol, a software package for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira (Mercury Inc.). Its main part is a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel). The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at a (near to) self-explanatory graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well. Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. Using the VIB protocol consequently may help to integrate knowledge on the correlation of form and function of the insect brain. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila. The software is freely available at http://www.neurofly.de.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Willmes2013,
  author    = {Willmes, Christoph},
  title     = {Therapie kutaner Tumoren : Identifizierung molekularer Biomarker der ex vivo Chemosensitivit{\"a}t des malignen Melanoms und Evaluierung der Wirkungsweise von Interferonen und Artemisininen auf das Merkelzellkarzinom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83470},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {F{\"u}r Patienten mit malignem Melanom im Stadium der Fernmetastasierung gibt es bis heute lediglich Therapieoptionen mit sehr eingeschr{\"a}nkten Erfolgsaussichten. Diese Tatsache best{\"a}tigt die Notwendigkeit von Biomarkern zur Vorhersage des Erfolgs verschiedener Therapien. Der ATP-basierende ex vivo Chemosensitivit{\"a}tsassay hat sich als erfolgreiche Methode zur individuellen Vorhersage eines Chemotherapieerfolgs herausgestellt. Tats{\"a}chlich zeigte der Assay ein heterogenes Sensitivit{\"a}tsprofil gegen verschiedene Chemotherapeutika und ließ in getesteten Patienten ein ex vivo wirksames Chemotherapieregime identifizieren, das anschließend auch klinische Therapieerfolge bei Verwendung der Therapie mit dem besten individuellen Chemosensitivit{\"a}tsindex(BICSI) zeigte. Um diesen sehr aufwendigen Assay zuk{\"u}nftig zu umgehen, sollten in der vorliegenden Arbeit pr{\"a}diktive molekulare Biomarker der Chemosensitivit{\"a}t identifiziert werden. Hierf{\"u}r wurden im Voraus durch einen Microarray die Kandidaten Secernin 1 (SCRN1), Lysyl oxidaselike 1 (LOXL1), Thymosin beta 4 X-linked (TMSB4X), Vesicle-associated membrane protein 5 (VAMP5) und Serine protease inhibitor B1 (SERPINB1) als differentiell exprimierte Gene in chemosensitivem gegen{\"u}ber chemoresistentem Gewebe identifiziert. Die relative Expression dieser Kandidatengene wurde daraufhin in bis zu 128 verschiedenen Melanomgeweben mit dem Chemosensitivit{\"a}tsindex verschiedener Chemotherapeutika korreliert. Hierbei konnte eine signifikante Korrelation zwischen SerpinB1 mit der Chemosensitivit{\"a}t gegen{\"u}ber der Therapiekombination mit Paclitaxel und Cisplatin auf Gen- aber nicht auf Proteinebene identifiziert werden. Weiterhin konnte eine differentielle Expression ebenfalls in chemosensitiven und -resistenten Melanomzelllinien nachgewiesen werden, die allerdings im Vergleich mit dem analysierten Gewebe in gegens{\"a}tzlicher Richtung verlief. Zusammenfassend l{\"a}sst sich sagen, dass SerpinB1 ein vielversprechender Marker f{\"u}r die Chemosensitivit{\"a}t gegen{\"u}ber Paclitaxel und Cisplatin ist, dessen funktionelle Bedeutung aber unklar bleibt. Das Merkelzellkarzinom (MCC) ist ein seltener und hoch aggressiver Tumor der mit dem Merkelzellpolyomavirus (MCV) in Zusammenhang steht. Da MCC Zelllinien zur Aufrechterhaltung ihrer Viabilit{\"a}t die MCV T-Antigene ben{\"o}tigen, k{\"o}nnte der Einsatz von Interferonen (IFN) ein m{\"o}glicher therapeutischer Ansatz zur Behandlung dieser Krebserkrankung sein. In der vorliegenden Arbeit haben wir daher die Effekte von IFNs auf MCC Zelllinien, mit besonderer Ber{\"u}cksichtigung der MCV+ Linien, untersucht. IFNs vom Typ I (hier Multiferon, ein Mix verschiedener IFN α Subtypen, und IFN β) wirkten stark inhibierend auf die zellul{\"a}re Viabilit{\"a}t. Die Zellzyklusanalyse zeigte eine Erh{\"o}hung des sub-G Anteils der Zellen nach Behandlung mit IFN, was auf Apoptose als ausschlagebenden Grund schließen ließ. Diese Effekte waren f{\"u}r die Behandlung mit IFN β weniger stark ausgepr{\"a}gt. Der inhibitorische Effekt von Typ I IFNs auf MCV+ MCC Zelllinien war assoziiert mit einer verringerten Expression des viralen großen T-Antigens (LTA) und einer Erh{\"o}hung in der Expression von promyelocytic leukemia protein (PML), das daf{\"u}r bekannt ist, die Funktion des LTA st{\"o}rend zu beeinflussen. Zus{\"a}tzlich f{\"u}hrte die intratumorale Anwendung von Multiferon in vivo zu einer Regression im Wachstum von MCV+, aber nicht MCV- MCC Xenotransplantaten. Die Ergebnisse zeigen das Typ I IFNs einen starken antitumoralen Effekt haben, der zum Teil durch die Regulierung des LTA herbeigef{\"u}hrt wird. Neben diesen direkten Effekten der IFNs auf die Zellproliferation induzieren diese auch die Expression von MHC Klasse I Molek{\"u}len in MCC Zelllinien. Die Durchflusszytometrie zeigte eine Induktion der MHC Klasse I Expression in drei MHC I negativen MCC Zelllinien und eine Erh{\"o}hung der Expression, die vor der Behandlung eine geringe Menge an MHC I aufwiesen. Diese Effekte konnten auch in den in vivo Xenotransplantaten beobachtet werden. Die Ergebnisse zeigen, dass die Behandlung mit IFN sowohl direkte als auch indirekte Effekte auf das MCC hat und eine breite Anwendung in Patienten mit MCV+ und MCV- Tumoren finden kann. Neben IFNs sind auch Artemisinin und seine Derivate bekannt f{\"u}r ihre antitumoralen und antiviralen Eigenschaften. Daher haben wir den Effekt des Artemisininderivats Artesunate auf MCV+ und MCV- MCC Zelllinien getestet. Tats{\"a}chlich konnten wir auch hier einen antiproliferativen Effekt des Stoffes nachweisen, der st{\"a}rker auf MCV+ als auf MCV- Zelllinien wirkte und bei ersteren wiederum mit einer reduzierten LTA Expression einherging. Im Vergleich dazu blieben Fibroblasten von der Behandlung unbeeinflusst. Das verringerte Tumorwachstum konnte ebenfalls f{\"u}r in vivo Xenotransplantationsmodelle gezeigt werden. Auf Grundlage dieser Erkenntnis sollte eine genauere Untersuchung dieses alten Naturheilstoffes f{\"u}r die Behandlung von MCC Patienten in Betracht gezogen werden.},
  subject      = {Interferon},
  language  = {de}
}
@phdthesis{Basile2009,
  author    = {Basile, Rebecca},
  title     = {Thermoregulation and Resource Management in the Honeybee (Apis mellifera)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39793},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Ein grundlegender Faktor, der f{\"u}r das {\"U}berleben einer Kolonie sozialer Insekten ausschlaggebend ist, liegt in der F{\"a}higkeit Nahrung durch sogenannte „Trophallaxis" auszutauschen. Diese F{\"u}tterungskontakte sorgen f{\"u}r die gleichm{\"a}ßige Verteilung der Nahrung innerhalb der Kolonie und werden als einer der Grundpfeiler der Sozialit{\"a}t der Staatenbildenden Insekten erachtet. Im Fall der Honigbienen finden diese Kontakte in vollkommener Dunkelheit statt. Damit es in dieser Situation {\"u}berhaupt zum Nahrungsaustausch kommen kann, sind die Antennen von großer Wichtigkeit. Ein erster Schritt in den Verhaltensweisen, die der Rezipient eines trophallaktischen Kontaktes zeigt, ist der Kontakt einer Antennenspitze mit den Mundwerkzeugen des Donoren, da sich dort die regurgitierte Nahrung befindet. Diese Ber{\"u}hrung hat aufgrund der gustatorischen Sensibilit{\"a}t der Antenne den Zweck, das angebotene Futter zu „erschmecken". Die rechte Antenne wird vom Rezipienten eines trophallaktischen Kontakts signifikant h{\"a}ufiger eingesetzt als die linke Antenne. Die Pr{\"a}ferenz f{\"u}r die rechte Antenne bleibt dabei auch erhalten, wenn ein Teil der Antennengeisel abgetrennt wurde, also die sensorischen F{\"a}higkeiten der rechten Antenne stark beeintr{\"a}chtigt wurden. Der Grund f{\"u}r die Pr{\"a}ferenz der rechten Antenne k{\"o}nnte ihrer erh{\"o}hten Sensibilit{\"a}t gegen{\"u}ber Zuckerwasser zugrunde liegen, da die rechte Antenne im Laborversuch signifikant st{\"a}rker auf Stimulationen mit Zuckerwasser verschiedener Konzentrationen reagierte als die linke. Trophallaktische Kontakte sichern Individuen innerhalb einer Kolonie den Zugang zur lebenswichtigen Nahrung. Im Beispiel der Honigbienen ist st{\"a}ndige Zugriff auf Nahrung besonders wichtig, da es sich um ein heterothermes Tier handelt, das die F{\"a}higkeit besitzt, aktiv seine K{\"o}rpertemperatur zu regulieren. Obgleich jedes Individuum in der Lage ist, seine K{\"o}rpertemperatur den eigenen Bed{\"u}rfnissen anzupassen, ist diese F{\"a}higkeit streng durch den in der Nahrung aufgenommenen Zucker reguliert. Im Gegensatz zu den S{\"a}ugetieren oder V{\"o}geln, die f{\"u}r eine Erh{\"o}hung des Blutzuckerspiegels auch auf Fett- oder Eiweißressourcen zur{\"u}ckgreifen k{\"o}nnen, ist die Honigbiene auf die Glucose aus der aufgenommenen Nahrung angewiesen. Die Ergebnisse dieser Untersuchung zeigen, dass der Zuckergehalt der aufgenommenen Nahrung positiv mit der Thoraxtemperatur der Bienen korreliert. Dieser Zusammenhang tritt auf, selbst wenn keine W{\"a}rmeerzeugung f{\"u}r die Brutpflege oder f{\"u}r das Erw{\"a}rmen der Wintertraube notwendig ist und die Tiere außerhalb des Stockes ohne eigentliche Notwendigkeit f{\"u}r die W{\"a}rmeerzeugung in einem K{\"a}fig gehalten werden. Die Ergebnisse der Untersuchung zeigen, dass die Rezipienten beim Nahrungsaustausch eine signifikant h{\"o}here Thoraxtemperatur haben als die Donoren. Außerdem zeigen die Rezipienten nach der F{\"u}tterung signifikant h{\"a}ufiger Brutw{\"a}rmeverhalten als die Donoren. Letztere haben eine signifikant niedrigere Thoraxtemperatur als die Rezipienten und zeigen eine Verhaltenstendenz, h{\"a}ufig zwischen Brutbereich und Honiglager hin- und her zu pendeln. Dabei nehmen sie im Honiglager Honig in ihren Kropf auf und f{\"u}ttern mit dieser Nahrung danach Bienen im Brutbereich. Außerdem zeigen die Ergebnisse, dass es einen w{\"a}rmegesteuerten Ausl{\"o}semechanismus gibt, der den Donoren und Rezipienten des trophallaktischen Kontakts dazu verhilft, trotz der Dunkelheit des Stocks praktisch verz{\"o}gerungsfreie Nahrungs{\"u}bertragung am Ort des h{\"o}chsten Energieverbrauchs zu gew{\"a}hrleisten. Das Hervorw{\"u}rgen von Nahrung angesichts einer W{\"a}rmequelle k{\"o}nnte seinen Ursprung in einer Beschwichtigungsgeste haben. Aggressive Tiere zeigen neben sichtbaren aggressiven Verhalten auch durch ihre erh{\"o}hte K{\"o}rpertemperatur, dass sie bereit sind sich auf einen Kampf einzulassen. Die Temperaturerh{\"o}hung eines aggressiven Tieres beruht dabei auf der erh{\"o}hten Muskelaktivit{\"a}t, die vor allem bei Insekten dazu n{\"o}tig ist, einen entsprechende Reaktion im Falle eines Kampfes oder der Flucht zeigen zu k{\"o}nnen. Wird ein Individuum mit Aggression konfrontiert, so bleibt ihm die Wahl sich auf einen Kampf einzulassen, zu fl{\"u}chten oder durch eine Beschwichtigungsgeste eine Deeskalation der Situation einzuleiten. Besonders h{\"a}ufig wird f{\"u}r diesen Zweck Nahrung regurgitiert und dem dominanteren Tier angeboten, um einem Konflikt aus dem Weg zu gehen. Die F{\"a}higkeit, Arbeiterinnen mit kleinen Portionen konzentrierter Nahrung zu versorgen tr{\"a}gt zu einer {\"o}konomischen Verteilung der Ressourcen bei, die mit den physiologischen Bed{\"u}rfnissen der Honigbienen konform geht und die {\"o}kologischen Erfordernisse des Stockes erf{\"u}llt. Das daraus resultierende Managementsystem, welches sparsam mit den Ressourcen haushaltet und auf die individuellen Bed{\"u}rfnisse jeder einzelnen Biene einzugehen vermag, k{\"o}nnte ein Grund f{\"u}r die F{\"a}higkeit der Honigbienen zur Entwicklung mehrj{\"a}hriger Kolonien sein, die, anders als Hummeln oder Wespen, auch den Winter in gem{\"a}ßigten Zonen als Gemeinschaft zu {\"u}berstehen verm{\"o}gen.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Bujok2005,
  author    = {Bujok, Brigitte},
  title     = {Thermoregulation im Brutbereich der Honigbiene Apis mellifera carnica},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-15903},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Honigbienen (Apis mellifera carnica) regulieren die Temperatur ihrer Brut in einem sehr engen Temperaturfenster, da vor allem die gedeckelte Brut sehr temperaturempfindlich reagiert (Groh et al. 2004). Die Thermoregulation ist nicht - wie lange angenommen - Beiprodukt von allt{\"a}glichen Arbeiten der Bienen im Brutbereich, sondern eine aktive und Energie- und Zeitaufw{\"a}ndige eigene T{\"a}tigkeit. Arbeiterinnen ziehen sich mit ihren Beinen an die Brutoberfl{\"a}che, dr{\"u}cken ihren warmen Thorax auf die Brutdeckel und verharren so f{\"u}r einige Minuten um mit der eigenen K{\"o}rperw{\"a}rme die Brut zu temperieren (Bujok et al. 2002). Wie erwartet korrelierte die Thoraxtemperatur einer Arbeiterin mit der Frequenz der abdominalen Atembewegungen, bei sehr hohen Thoraxtemperaturen ({\"u}ber 40°C) erreichten die Bienen Atemfrequenzen von {\"u}ber 8Hz. Eine weitere Methode die Brut effektiv zu w{\"a}rmen {\"u}bten Bienen aus, die leere Zellen im gedeckelten Brutbereich besuchen (Kleinhenz et al. 2003). Arbeiterinnen gingen dabei bevorzugt in Zellen, die von m{\"o}glichst vielen gedeckelten Zellen umgeben waren. Sowohl die Dauer der Zellbesuche, als auch die mittlere Thoraxtemperatur bei Ein- und Austritt der Zelle korrelierten mit der Anzahl der benachbarten Brutzellen - je mehr Brutzellen eine leere Zelle in ihrer direkten Nachbarschaft hatte umso l{\"a}nger dauerte der Besuch einer Biene und umso h{\"o}her ist die Ein- bzw. Austrittstemperatur der Biene. Mindestes 48 Stunden alte Bienen unterschieden sich signifikant in ihrem W{\"a}rmeverhalten von j{\"u}ngeren Bienen. Tote gedeckelte Brut wurde in manchen F{\"a}llen {\"u}ber viele Tage (durchgehend bis 10 Tage) gew{\"a}rmt, sie unterschied sich in ihrer Temperatur nicht von unbehandelter gedeckelter Brut. In weiteren Versuchen lag die Bruttemperatur von toter Brut zwar unter der eines Kontrollbereiches, die Temperatur lag aber weiterhin im optimalen Bereich von 33,5 bis 35°C (Groh et al. 2004). In diesen Versuchen wurde die tote Brut vor dem Einsetzen in den Beobachtungsstock wieder auf 35°C erw{\"a}rmt. Wachskegel in gedeckelten Zellen wurden erkannt und ausger{\"a}umt. Aktive Signale, die von der Brut ausgehen scheinen also nicht notwendig f{\"u}r die effektive Bruttemperaturregulierung zu sein. Untersuchungen mittels Laser-Doppler-Vibrometrie zeigten auch keine Hinweise auf eine mechanische Kommunikation zwischen den Puppen und den Arbeiterinnen. Das Brutw{\"a}rmen scheint eine Aktion zu sein, die von den Bienen nur in Gemeinschaft sinnvoll durchgef{\"u}hrt werden kann. In einigen F{\"a}llen kam es w{\"a}hrend der Puppenphase zu unerkl{\"a}rlichen Abf{\"a}llen in der Bruttemperatur, die nur durch einen positiven R{\"u}ckkopplungseffekt seitens der Arbeiterinnen erkl{\"a}rt werden kann. Beim Brutw{\"a}rmen spielen die Antennen der Arbeiterinnen wahrscheinlich eine wichtige Rolle. W{\"a}hrend sich die Bienen beim aktiven Brutw{\"a}rmen den Brutdeckel ann{\"a}hern sind die Antennenspitzen immer auf die Brutdeckel gerichtet. Fehlen den Arbeiterinnen die Antennen, dann ist die Thermoregulation eingeschr{\"a}nkt oder unzureichend. Die Bruttemperatur korreliert mit der Anzahl der abgetrennten Antennensegmente, je mehr Antennensegmente fehlen, desto weniger gut wird die Temperatur im Brutbereich hoch und konstant gehalten. Zus{\"a}tzlich scheint es eine Lateralit{\"a}t in der Antennenfunktion zu geben, wurde die rechte Antenne gek{\"u}rzt w{\"a}rmten die Bienen die Brut signifikant schlechter, als beim K{\"u}rzen der linken Antenne. Durch das K{\"u}rzen der Antennen {\"a}nderte sich auch das Verhalten der Tiere: Kontrollbienen verharrten ruhig im Brutbereich, w{\"a}hrend Bienen mit gek{\"u}rzten Antennen teilweise {\"a}hnlich warm waren, aber nicht mehr das oben beschriebene aktive Brutw{\"a}rmeverhalten zeigten.},
  subject      = {Biene},
  language  = {de}
}
@phdthesis{Nuernberger2018,
  author    = {N{\"u}rnberger, Fabian},
  title     = {Timing of colony phenology and foraging activity in honey bees},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155105},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {I. Timing is a crucial feature in organisms that live within a variable and changing environment. Complex mechanisms to measure time are wide-spread and were shown to exist in many taxa. These mechanisms are expected to provide fitness benefits by enabling organisms to anticipate environmental changes and adapt accordingly. However, very few studies have addressed the adaptive value of proper timing. The objective of this PhD-project was to investigate mechanisms and fitness consequences of timing decisions concerning colony phenology and foraging activity in the honey bee (Apis mellifera), a social insect species with a high degree of social organization and one of the most important pollinators of wild plants and crops. In chapter II, a study is presented that aimed to identify the consequences of disrupted synchrony between colony phenology and the local environment by manipulating the timing of brood onset after hibernation. In a follow-up experiment, the importance of environmental factors for the timing of brood onset was investigated to assess the potential of climate change to disrupt synchronization of colony phenology (Chapter III). Chapter IV aimed to prove for the first time that honey bees can use interval time-place learning to improve foraging activity in a variable environment. Chapter V investigates the fitness benefits of information exchange between nest mates via waggle dance communication about a resource environment that is heterogeneous in space and time. II. In the study presented in chapter II, the importance of the timing of brood onset after hibernation as critical point in honey bee colony phenology in temperate zones was investigated. Honey bee colonies were overwintered at two climatically different sites. By translocating colonies from each site to the other in late winter, timing of brood onset was manipulated and consequently colony phenology was desynchronized with the local environment. Delaying colony phenology in respect to the local environment decreased the capability of colonies to exploit the abundant spring bloom. Early brood onset, on the other hand, increased the loads of the brood parasite Varroa destructor later in the season with negative impact on colony worker population size. This indicates a timing related trade-off and illustrates the importance of investigating effects of climate change on complex multi-trophic systems. It can be concluded that timing of brood onset in honey bees is an important fitness relevant step for colony phenology that is highly sensitive to climatic conditions in late winter. Further, phenology shifts and mismatches driven by climate change can have severe fitness consequences. III. In chapter III, I assess the importance of the environmental factors ambient temperature and photoperiod as well as elapsed time on the timing of brood onset. Twenty-four hibernating honey bee colonies were placed into environmental chambers and allocated to different combinations of two temperature regimes and three different light regimes. Brood onset was identified non-invasively by tracking comb temperature within the winter cluster. The experiment revealed that ambient temperature plays a major role in the timing of brood onset, but the response of honey bee colonies to temperature increases is modified by photoperiod. Further, the data indicate the involvement of an internal clock. I conclude that the timing of brood onset is complex but probably highly susceptible to climate change and especially spells of warm weather in winter. IV. In chapter IV, it was examined if honey bees are capable of interval time-place learning and if this ability improves foraging efficiency in a dynamic resource environment. In a field experiment with artificial feeders, foragers were able to learn time intervals and use this ability to anticipate time periods during which feeders were active. Further, interval time-place learning enabled foragers to increase nectar uptake rates. It was concluded that interval time-place learning can help honey bee foragers to adapt to the complex and variable temporal patterns of floral resource environments. V. The study presented in chapter V identified the importance of the honey bee waggle dance communication for the spatiotemporal coordination of honey bee foraging activity in resource environments that can vary from day to day. Consequences of disrupting the instructional component of honey bee dance communication were investigated in eight temperate zone landscapes with different levels of spatiotemporal complexity. While nectar uptake of colonies was not affected, waggle dance communication significantly benefitted pollen harvest irrespective of landscape complexity. I suggest that this is explained by the fact that honey bees prefer to forage pollen in semi-natural habitats, which provide diverse resource species but are sparse and presumably hard to find in intensively managed agricultural landscapes. I conclude that waggle dance communication helps to ensure a sufficient and diverse pollen diet which is crucial for honey bee colony health. VI. In my PhD-project, I could show that honey bee colonies are able to adapt their activities to a seasonally and daily changing environment, which affects resource uptake, colony development, colony health and ultimately colony fitness. Ongoing global change, however, puts timing in honey bee colonies at risk. Climate change has the potential to cause mismatches with the local resource environment. Intensivation of agricultural management with decreased resource diversity and short resource peaks in spring followed by distinctive gaps increases the probability of mismatches. Even the highly efficient foraging system of honey bees might not ensure a sufficiently diverse and healthy diet in such an environment. The global introduction of the parasitic mite V. destructor and the increased exposure to pesticides in intensively managed landscapes further degrades honey bee colony health. This might lead to reduced cognitive capabilities in workers and impact the communication and social organization in colonies, thereby undermining the ability of honey bee colonies to adapt to their environment.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{SchenkneeWolf2018,
  author    = {Schenk [n{\´e}e Wolf], Mariela},
  title     = {Timing of wild bee emergence: mechanisms and fitness consequences},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161565},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Solitary bees in seasonal environments have to align their life-cycles with favorable environmental conditions and resources. Therefore, a proper timing of their seasonal activity is highly fitness relevant. Most species in temperate environments use temperature as a trigger for the timing of their seasonal activity. Hence, global warming can disrupt mutualistic interactions between solitary bees and plants if increasing temperatures differently change the timing of interaction partners. The objective of this dissertation was to investigate the mechanisms of timing in spring-emerging solitary bees as well as the resulting fitness consequences if temporal mismatches with their host plants should occur. In my experiments, I focused on spring-emerging solitary bees of the genus Osmia and thereby mainly on O. cornuta and O. bicornis (in one study which is presented in Chapter IV, I additionally investigated a third species: O. brevicornis). Chapter II presents a study in which I investigated different triggers solitary bees are using to time their emergence in spring. In a climate chamber experiment I investigated the relationship between overwintering temperature, body size, body weight and emergence date. In addition, I developed a simple mechanistic model that allowed me to unite my different observations in a consistent framework. In combination with the empirical data, the model strongly suggests that solitary bees follow a strategic approach and emerge at a date that is most profitable for their individual fitness expectations. I have shown that this date is on the one hand temperature dependent as warmer overwintering temperatures increase the weight loss of bees during hibernation, which then advances their optimal emergence date to an earlier time point (due to an earlier benefit from the emergence event). On the other hand I have also shown that the optimal emergence date depends on the individual body size (or body weight) as bees adjust their emergence date accordingly. My data show that it is not enough to solely investigate temperature effects on the timing of bee emergence, but that we should also consider individual body conditions of solitary bees to understand the timing of bee emergence. In Chapter III, I present a study in which I investigated how exactly temperature determines the emergence date of solitary bees. Therefore, I tested several variants degree-day models to relate temperature time series to emergence data. The basic functioning of such degree-day models is that bees are said to finally emerge when a critical amount of degree-days is accumulated. I showed that bees accumulate degree-days only above a critical temperature value (~4°C in O. cornuta and ~7°C in O. bicornis) and only after the exceedance of a critical calendar date (~10th of March in O. cornuta and ~28th of March in O. bicornis). Such a critical calendar date, before which degree-days are not accumulated irrespective of the actual temperature, is in general less commonly used and, so far, it has only been included twice in a phenology model predicting bee emergence. Furthermore, I used this model to retrospectively predict the emergence dates of bees by applying the model to long-term temperature data which have been recorded by the regional climate station in W{\"u}rzburg. By doing so, the model estimated that over the last 63 years, bees emerged approximately 4 days earlier. In Chapter IV, I present a study in which I investigated how temporal mismatches in bee-plant interactions affect the fitness of solitary bees. Therefore, I performed an experiment with large flight cages serving as mesocosms. Inside these mesocosms, I manipulated the supply of blossoms to synchronize or desynchronize bee-plant interactions. In sum, I showed that even short temporal mismatches of three and six days in bee-plant interactions (with solitary bee emergence before flower occurrence) can cause severe fitness losses in solitary bees. Nonetheless, I detected different strategies by solitary bees to counteract impacts on their fitness after temporal mismatches. However, since these strategies may result in secondary fitness costs by a changed sex ratio or increased parasitism, I concluded that compensation strategies do not fully mitigate fitness losses of bees after short temporal mismatches with their food plants. In the event of further climate warming, fitness losses after temporal mismatches may not only exacerbate bee declines but may also reduce pollination services for later-flowering species and affect populations of animal-pollinated plants. In conclusion, I showed that spring-emerging solitary bees are susceptible to climate change as in response to warmer temperatures bees advance their phenology and show a decreased fitness state. As spring-emerging solitary bees not only consider overwintering temperature but also their individual body condition for adjusting emergence dates, this may explain differing responses to climate warming within and among bee populations which may also have consequences for bee-plant interactions and the persistence of bee populations under further climate warming. If in response to climate warming plants do not shift their phenologies according to the bees, bees may experience temporal mismatches with their host plants. As bees failed to show a single compensation strategy that was entirely successful in mitigating fitness consequences after temporal mismatches with their food plants, the resulting fitness consequences for spring-emerging solitary bees would be severe. Furthermore, I showed that spring-emerging solitary bees use a critical calendar date before which they generally do not commence the summation of degree-days irrespective of the actual temperature. I therefore suggest that further studies should also include the parameter of a critical calendar date into degree-day model predictions to increase the accuracy of model predictions for emergence dates in solitary bees. Although our retrospective prediction about the advance in bee emergence corresponds to the results of several studies on phenological trends of different plant species, we suggest that more research has to be done to assess the impacts of climate warming on the synchronization in bee-plant interactions more accurately.},
  subject      = {wild bees},
  language  = {en}
}
@phdthesis{Liang2009,
  author    = {Liang, Chunguang},
  title     = {Tools for functional genomics applied to Staphylococci, Listeriae, Vaccinia virus and other organisms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48051},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Genome sequence analysis A combination of genome analysis application has been established here during this project. This offers an efficient platform to interactively compare similar genome regions and reveal loci differences. The genes and operons can be rapidly analyzed and local collinear blocks (LCBs) categorized according to their function. The features of interests are parsed, recognized, and clustered into reports. Phylogenetic relationships can be readily examined such as the evolution of critical factors or a certain highly-conserved region. The resulting platform-independent software packages (GENOVA and inGeno), have been proven to be efficient and easy to handle in a number of projects. The capabilities of the software allowed the investigation of virulence factors, e.g., rsbU, strains' biological design, and in particular pathogenicity feature storage and management. We have successfully investigated the genomes of Staphylococcus aureus strains (COL, N315, 8325, RN1HG, Newman), Listeria spp. (welshimeri, innocua and monocytogenes), E.coli strains (O157:H7 and MG1655) and Vaccinia strains (WR, Copenhagen, Lister, LIVP, GLV-1h68 and parental strains). Metabolic network analysis Our YANAsquare package offers a workbench to rapidly establish the metabolic network of such as Staphylococcous aureus bacteria in genome-scale size as well as metabolic networks of interest such as the murine phagosome lipid signalling network. YANAsquare recruits reactions from online databases using an integrated KEGG browser. This reduces the efforts in building large metabolic networks. The involved calculation routines (METATOOL-derived wrapper or native Java implementation) readily obtain all possible flux modes (EM/EP) for metabolite fluxes within the network. Advanced layout algorithms visualize the topological structure of the network. In addition, the generated structure can be dynamically modified in the graphic interface. The generated network as well as the manipulated layout can be validated and stored (XML file: scheme of SBML level-2). This format can be further parsed and analyzed by other systems biology software, such as CellDesigner. Moreover, the integrated robustness-evaluation routine is able to examine the synthesis rates affected by each single mutation throughout the whole network. We have successfully applied the method to simulate single and multiple gene knockouts, and the affected fluxes are comprehensively revealed. Recently we applied the method to proteomic data and extra-cellular metabolite data of Staphylococci, the physiological changes regarding the flux distribution are studied. Calculations at different time points, including different conditions such as hypoxia or stress, show a good fit to experimental data. Moreover, using the proteomic data (enzyme amounts) calculated from 2D-Gel-EP experiments our study provides a way to compare the fluxome and the enzyme expression. Oncolytic vaccinia virus (VACV) We investigated the genetic differences between the de novo sequence of the recombinant oncolytic GLV-1h68 and other related VACVs, including function predictions for all found genome differences. Our phylogenetic analysis indicates that GLV-1h68 is closest to Lister strains but has lost several ORFs present in its parental LIVP strain, including genes encoding CrmE and a viral Golgi anti-apoptotic protein, v-GAAP. Functions of viral genes were either strain-specific, tissue-specific or host-specific comparing viral genes in the Lister, WR and COP strains. This helps to rationally design more optimized oncolytic virus strains to benefit cancer therapy in human patients. Identified differences from the comparison in open reading frames (ORFs) include genes for host-range selection, virulence and immune modulation proteins, e.g. ankyrin-like proteins, serine proteinase inhibitor SPI-2/CrmA, tumor necrosis factor (TNF) receptor homolog CrmC, semaphorin-like and interleukin-1 receptor homolog proteins. The contribution of foreign gene expression cassettes in the therapeutic and oncolytic virus GLV-1h68 was studied, including the F14.5L, J2R and A56R loci. The contribution of F14.5L inactivation to the reduced virulence is demonstrated by comparing the virulence data of GLV-1h68 with its F14.5L-null and revertant viruses. The comparison suggests that insertion of a foreign gene expression cassette in a nonessential locus in the viral genome is a practical way to attenuate VACVs, especially if the nonessential locus itself contains a virulence gene. This reduces the virulence of the virus without compromising too much the replication competency of the virus, the key to its oncolytic activity. The reduced pathogenicity of GLV-1h68 was confirmed by our experimental collaboration partners in male mice bearing C6 rat glioma and in immunocompetent mice bearing B16-F10 murine melanoma. In conclusion, bioinformatics and experimental data show that GLV-1h68 is a promising engineered VACV variant for anticancer therapy with tumor-specific replication, reduced pathogenicity and benign tissue tropism.},
  subject      = {Genanalyse},
  language  = {en}
}
@phdthesis{Griffoni2019,
  author    = {Griffoni, Chiara},
  title     = {Towards advanced immunocompetent skin wound models for in vitro drug evaluation},
  doi       = {10.25972/OPUS-19212},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-192125},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {Current preclinical models used to evaluate novel therapies for improved healing include both in vitro and in vivo methods. However, ethical concerns related to the use of animals as well as the poor physiological translation between animal and human skin wound healing designate in vitro models as a highly relevant and promising platforms for healing investigation. While current in vitro 3D skin models recapitulate a mature tissue with healing properties, they still represent a simplification of the in vivo conditions, where for example the inflammatory response originating after wound formation involves the contribution of immune cells. Macrophages are among the main contributors to the inflammatory response and regulate its course thanks to their plasticity. Therefore, their implementation into in vitro skin could greatly increase the physiological relevance of the models. As no full-thickness immunocompetent skin model containing macrophages has been reported so far, the parameters necessary for a successful triple co-culture of fibroblasts, keratinocytes and macrophages were here investigated. At first, cell source and culture timed but also an implementation strategy for macrophages were deter-mined. The implementation of macrophages into the skin model focused on the minimization of the culture time to preserve immune cell viability and phenotype, as the environment has a major influence on cell polarization and cytokine production. To this end, incorporation of macrophages in 3D gels prior to the combination with skin models was selected to better mimic the in vivo environment. Em-bedded in collagen hydrogels, macrophages displayed a homogeneous cell distribution within the gel, preserving cell viability, their ability to respond to stimuli and their capability to migrate through the matrix, which are all needed during the involvement of macrophages in the inflammatory response. Once established how to introduce macrophages into skin models, different culture media were evaluated for their effects on primary fibroblasts, keratinocytes and macrophages, to identify a suitable medium composition for the culture of immunocompetent skin. The present work confirmed that each cell type requires a different supplement combination for maintaining functional features and showed for the first time that media that promote and maintain a mature skin structure have negative effects on primary macrophages. Skin differentiation media negatively affected macrophages in terms of viability, morphology, ability to respond to pro- and anti-inflammatory stimuli and to migrate through a collagen gel. The combination of wounded skin equivalents and macrophage-containing gels con-firmed that culture medium inhibits macrophage participation in the inflammatory response that oc-curs after wounding. The described macrophage inclusion method for immunocompetent skin creation is a promising approach for generating more relevant skin models. Further optimization of the co-cul-ture medium will potentially allow mimicking a physiological inflammatory response, enabling to eval-uate the effects novel drugs designed for improved healing on improved in vitro models.},
  subject      = {Haut},
  language  = {en}
}
@phdthesis{Michels2008,
  author    = {Michels, Birgit},
  title     = {Towards localizing the Synapsin-dependent olfactory memory trace in the brain of larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-36338},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Animals need to adapt and modify their behaviour according to a changing environment. In particular, the ability to learn about rewarding or punishing events is crucial for survival. One key process that underlies such learning are modifications of the synaptic connection between nerve cells. This Thesis is concerned with the genetic determinants of such plasticity, and with the site of these modifications along the sensory-to-motor loops in Drosophila olfactory learning. I contributed to the development and detailed parametric description of an olfactory associative learning paradigm in larval fruit flies (Chapter I.1.). The robustness of this learning assay, together with a set of transgenic Drosophila strains established during this Thesis, enabled me to study the role for Synapsin, a presynaptic phosphoprotein likely involved in synaptic plasticity, in this form of learning (Chapter I.2.), and to investigate the cellular site of the corresponding Synapsin-dependent memory trace (Chapter I.3.). These data provide the first comprehensive account to-date of the neurogenetic bases of learning in larval Drosophila. The role for Synapsin was also analyzed with regard to pain-relief learning in adult fruit flies (Chapter II.1.); that is, if an odour precedes an electric shock during training, flies subsequently avoid that odour ('punishment learning'), whereas presentation of the odour upon the cessation of shock subsequently leads to approach towards the odour ('relief larning'). Such pain-relief learning was also the central topic of a study concerning the white gene (Chapter II.2.), which as we report does affect pain-relief as well as punishment learning in adult flies, but leaves larval odour-food learning unaffected. These studies regarding pain-relief learning provide the very first hints, in any experimental system, concerning the genetic determinants of this form of learning.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Fink2008,
  author    = {Fink, Kristin},
  title     = {Toxins in Renal Disease and Dialysis Therapy : Genotoxic Potential and Mechanisms},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31082},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {In patients suffering from end-stage renal disease who are treated by hemodialysis genomic damage as well as cancer incidence is elevated. One possible cause for the increased genomic damage could be the accumulation of genotoxic substances in the blood of patients. Two possible sources for those toxins have to be considered. The first possibility is that substances from dialysers, the blood tubing system or even contaminated dialysis solutions may leach into the blood of the patients during dialysis. Secondly, the loss of renal filtration leads to an accumulation of substances which are normally excreted by the kidney. If those substances possess toxic potential, they are called uremic toxins. Several of these uremic toxins are potentially genotoxic. Within this thesis several exemplary uremic toxins have been tested for genotoxic effects (homocysteine, homocysteine-thiolactone,leptine, advanced glycated end-products). Additionally, it was analysed whether substances are leaching from dialysers or blood tubing and whether they cause effects in in vitrotoxicity testing. The focus of chemical analytisis was on bisphenol A (BPA), the main component of plastics used in dialysers and dialyser membranes.},
  subject      = {Bisphenol A},
  language  = {en}
}
@phdthesis{Eidel2020,
  author    = {Eidel, Matthias T. A. M.},
  title     = {Training Effects of a Tactile Brain-Computer Interface System During Prolonged Use by Healthy And Motor-Impaired People},
  doi       = {10.25972/OPUS-20851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208511},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Background - Brain-Computer Interfaces (BCI) enable their users to interact and communicate with the environment without requiring intact muscle control. To this end, brain activity is directly measured, digitized and interpreted by the computer. Thus, BCIs may be a valuable tool to assist severely or even completely paralysed patients. Many BCIs, however, rely on neurophysiological potentials evoked by visual stimulation, which can result in usability issues among patients with impaired vision or gaze control. Because of this, several non-visual BCI paradigms have been developed. Most notably, a recent study revealed promising results from a tactile BCI for wheelchair control. In this multi-session approach, healthy participants used the BCI to navigate a simulated wheelchair through a virtual apartment, which revealed not only that the BCI could be operated highly efficiently, but also that it could be trained over five sessions. The present thesis continues the research on this paradigm in order to - confirm its previously reported high performance levels and trainability - reveal the underlying factors responsible for observed performance increases - establish its feasibility among potential impaired end-users Methods - To approach these goals, three studies were conducted with both healthy participants and patients with amyotrophic lateral sclerosis (ALS). Brain activity during BCI operation was recorded via electroencephalography (EEG) and interpreted using a machine learning-based linear classifier. Wheelchair navigation was executed according to the classification results and visualized on a monitor. For offline statistical analysis, neurophysiological features were extracted from EEG data. Subjective data on usability were collected from all participants. Two specialized experiments were conducted to identify factors for training. Results and Discussion - Healthy participants: Results revealed positive effects of training on BCI performances and their underlying neurophysiological potentials. The paradigm was confirmed to be feasible and (for a non-visual BCI) highly efficient for most participants. However, some had to be excluded from analysis of the training effects because they could not achieve meaningful BCI control. Increased somatosensory sensitivity was identified as a possible mediator for training-related performance improvements. Participants with ALS: Out of seven patients with various stages of ALS, five could operate the BCI with accuracies significantly above chance level. Another ALS patient in a state of near-complete paralysis trained with the BCI for several months. Although no effects of training were observed, he was consistently able to operate the system above chance level. Subjective data regarding workload, satisfaction and other parameters were reported. Significance - The tactile BCI was evaluated on the example of wheelchair control. In the future, it could help impaired patients to regain some lost mobility and self-sufficiency. Further, it has the potential to be adapted to other purposes, including communication. Once visual BCIs and other assistive technologies fail for patients with (progressive) motor impairments, vision-independent paradigms such as the tactile BCI may be among the last remaining alternatives to interact with the environment. The present thesis has strongly confirmed the general feasibility of the tactile paradigm for healthy participants and provides first clues about the underlying factors of training. More importantly, the BCI was established among potential end-users with ALS, providing essential external validity.},
  subject      = {Myatrophische Lateralsklerose},
  language  = {en}
}
@phdthesis{Aroko2024,
  author    = {Aroko, Erick Onyango},
  title     = {Trans-regulation of \(Trypanosoma\) \(brucei\) variant surface glycoprotein (VSG) mRNA and structural analysis of a \(Trypanosoma\) \(vivax\) VSG using X-ray crystallography},
  doi       = {10.25972/OPUS-24177},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241773},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {African trypanosomes are unicellular parasites that cause nagana and sleeping sickness in livestock and man, respectively. The major pathogens for the animal disease include Trypanosoma vivax, T. congolense, and T. brucei brucei, whereas T. b. gambiense and T. b. rhodesiense are responsible for human infections. Given that the bloodstream form (BSF) of African trypanosomes is exclusively extracellular, its cell surface forms a critical boundary with the host environment. The cell surface of the BSF African trypanosomes is covered by a dense coat of immunogenic variant surface glycoproteins (VSGs). This surface protein acts as an impenetrable shield that protects the cells from host immune factors and is also involved in antibody clearance and antigenic variation, which collectively ensure that the parasite stays ahead of the host immune system. Gene expression in T. brucei is markedly different from other eukaryotes: most genes are transcribed as long polycistronic units, processed by trans-splicing a 39-nucleotide mini exon at the 5′ and polyadenylation at the 3′ ends of individual genes to generate the mature mRNA. Therefore, gene expression in T. brucei is regulated post-transcriptionally, mainly by the action of RNA binding proteins (RBPs) and conserved elements in the 3′ untranslated regions (UTR) of transcripts. The expression of VSGs is highly regulated, and only a single VSG gene is expressed at a time from one of the ~15 subtelomeric domains termed bloodstream expression sites (BES). When cells are engineered to simultaneously express two VSGs, the total VSG mRNA do not exceed the wild type amounts. This suggests that a robust VSG mRNA balancing mechanism exists in T. brucei. The present study uses inducible and constitutive expression of ectopic VSG genes to show that the endogenous VSG mRNA is regulated only if the second VSG is properly targeted to the ER. Additionally, the endogenous VSG mRNA response is triggered when high amounts of the GFP reporter with a VSG 3′UTR is targeted to the ER. Further evidence that non-VSG ER import signals can efficiently target VSGs to the ER is presented. This study suggests that a robust trans-regulation of the VSG mRNA is elicited at the ER through a feedback loop to keep the VSG transcripts in check and avoid overshooting the secretory pathway capacity. Further, it was shown that induction of expression of the T. vivax VSG ILDat1.2 in T. brucei causes a dual cell cycle arrest, with concomitant upregulation of the protein associated with differentiation (PAD1) expression. It could be shown that T. vivax VSG ILDat1.2 can only be sufficiently expressed in T. brucei after replacing its native GPI signal peptide with that of a T. brucei VSG. Taken together, these data indicate that inefficient VSG GPI anchoring and expression of low levels of the VSG protein can trigger differentiation from slender BSF to stumpy forms. However, a second T. vivax VSG, ILDat2.1, is not expressed in T. brucei even after similar modifications to its GPI signals. An X-ray crystallography approach was utilized to solve the N-terminal domain (NTD) structure of VSG ILDat1.2. This is first structure of a non-T. brucei VSG, and the first of a surface protein of T. vivax to be solved. VSG ILDat1.2 NTD maintains the three-helical bundle scaffold conserved in T. brucei surface proteins. However, it is likely that there are variations in the architecture of the membrane proximal region of the ILDat1.2 NTD and its CTD from T. brucei VSGs. The tractable T. brucei system is presented as a model that can be used to study surface proteins of related trypanosome species, thus creating avenues for further characterization of trypanosome surface coats.},
  subject      = {Trypanosoma vivax},
  language  = {en}
}