@phdthesis{Ulrich2012,
  author    = {Ulrich, Tanja},
  title     = {Function of Lin9 in vivo and MAP3K4-p38 signaling regulates p53 mediated cell cycle arrest after defective mitosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73975},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Eine genaue Kontrolle des Verlaufs durch die Mitose ist entscheidend f{\"u}r die Gew{\"a}hrleistung genomischer Stabilit{\"a}t und f{\"u}r die Vermeidung von Aneuploidy. Der DREAM Komplex ist ein wichtiger Regulator der Expression von mitotischen Genen. Die Depletion der DREAM-Untereinheit Lin9, f{\"u}hrt zu einer verminderten Expression von G2/M Genen und beeintr{\"a}chtigt die Proliferation. In konditionellen knockout Mauszellen (MEFs) verursacht das Ausschalten von Lin9 Defekte in Mitose und Zytokinese und l{\"o}st vorzeitige Seneszenz aus, um eine weitere Zellproliferation zu verhindern. In dieser Arbeit konnte gezeigt werden, dass der seneszente Ph{\"a}notyp in Lin9 knockout MEFs unabh{\"a}ngig von den beiden Tumorsuppressor-Signalwegen p53-p21 und p16-pRB induziert wird. Untersuchungen mit dem konditionellen Lin9 knockout Mausmodell verdeutlichten die wichtige Funktion von Lin9 in der Regulierung der mitotischen Genexpression und der Proliferation in vivo. Das Fehlen von Lin9 f{\"u}hrte zu einer verringerten Proliferation in den Krypten des D{\"u}nndarms und verursachte eine Atrophie des Darmepithels und einen schnell eintretenden Tod der Tiere. Im zweiten Teil der Arbeit wurden Signalwege untersucht, die nach fehlerhafter Zytokinese zu einem p53 vermittelten G1-Arrest f{\"u}hren. Hierf{\"u}r wurde ein chemischer Inhibitor der mitotischen Kinase Aurora B verwendet. Mit Hilfe eines Hochdurchsatz siRNA Screens wurde die MAP Kinase MAP3K4 als Aktivator des p53 Signalwegs identifiziert. Es konnte gezeigt werden, dass MAP3K4 die Stresskinase p38b aktiviert, um den p53 vermittelten Zellzyklusarrest in tetraploiden Zellen auszul{\"o}sen. Dabei wurde p38b nach Hemmung von Aurora B f{\"u}r die transkriptionelle Aktivierung des p53 Zielgens p21 ben{\"o}tigt. Im Gegenteil dazu erfolgte die Phosphorylierung, Stabilisierung und die Rekrutierung von p53 an den p21 Promoter unabh{\"a}ngig von p38. Die teilweise Hemmung von Aurora B zeigte, dass fehlerhafte Segregation von Chromosomen auch den MAP3K4-p38-p53 Signalweg aktiviert und l{\"a}sst darauf schließen, dass subtile Defekte in der Mitose ausreichen diesen Stress-Signalweg zu induzieren. Obwohl p38 f{\"u}r den G1 Zellzyklusarrest nach mitotischen Sch{\"a}den erforderlich war, f{\"u}hrte die gleichzeitige Inhibierung von p38 und Aurora B {\"u}ber einen l{\"a}ngeren Zeitraum zu einer verringerten Proliferation, vermutlich aufgrund verst{\"a}rkter Apoptose. Es ist anzunehmen, dass der MAP3K4-p38-p53 Signalweg generell nach Defekten in der Mitose oder Zytokinese aktiviert wird um Zellen in G1 zu arretieren und um chromosomale Instabilit{\"a}t zu vermeiden.},
  subject      = {Mitose},
  language  = {en}
}
@phdthesis{Hsieh2011,
  author    = {Hsieh, Samuel Yu-Lung},
  title     = {The diversity and ecology of the spider communities of European beech canopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66966},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Ein wesentliches Ziel {\"o}kologischer Forschung ist es, die Frage zu beantworten, wie Arten koexistieren k{\"o}nnen und die biologische Vielfalt erhalten bleibt. Um zu verstehen, wie dabei Gemeinschaften in unterschiedlichen r{\"a}umlich-zeitlichen Dimensionen interagieren, um die biologische Vielfalt zu erhalten, ist ein umfassendes prozessorientiertes Wissen erforderlich. Demzufolge konzentrierte sich meine Studie im Wesentlichen auf die Biodiversit{\"a}t und die sie beeinflussenden raum-zeitlichen {\"o}kologischen Prozesse. Vergleicht man die {\"A}hnlich- bzw. Un{\"a}hnlichkeit der in verschieden alten Best{\"a}nden lebenden Spinnengemeinschaften der Buchen (Fagus sylvatica L.), dann zeigt sich, dass die {\"a}lteste Baumkohorte offensichtlich einzigartige Ressourcen besitzt, welche die Zusammensetzung der Spinnengemeinschaften deutlich pr{\"a}gen. {\"U}ber das Jahr hin zeigten die Spinnengemeinschaften trotz der jahreszeitlich unterschiedlich {\"o}kologischen Randbedingungen eine sich wiederholende, vorhersehbare Dynamik. Der Vergleich {\"u}ber die Jahre ergab, dass das "Neutrale Modell" und das "Nischen-Modell" gleichzeitig funktionieren k{\"o}nnen. Beide sind notwendig, um die Dynamik der in den Buchenkronen der verschiedenen Altersklassen lebenden Spinnengemeinschaften vollst{\"a}ndig erkl{\"a}ren zu k{\"o}nnen.},
  subject      = {Spinnen},
  language  = {en}
}
@phdthesis{Schul2013,
  author    = {Schul, Daniela},
  title     = {Spatio-temporal investigation and quantitative analysis of the BMP signaling pathway},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-84224},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Bone Morphogenetic Proteins (BMPs) are key regulators for a lot of diverse cellular processes. During embryonic development these proteins act as morphogens and play a crucial role particularly in organogenesis. BMPs have a direct impact on distinct cellular fates by means of concentration-gradients in the developing embryos. Using the diverse signaling input information within the embryo due to the gradient, the cells transduce the varying extracellular information into distinct gene expression profiles and cell fate decisions. Furthermore, BMP proteins bear important functions in adult organisms like tissue homeostasis or regeneration. In contrast to TGF-ß signaling, currently only little is known about how cells decode and quantify incoming BMP signals. There is poor knowledge about the quantitative relationships between signal input, transducing molecules, their states and location, and finally their ability to incorporate graded systemic inputs and produce qualitative responses. A key requirement for efficient pathway modulation is the complete comprehension of this signaling network on a quantitative level as the BMP signaling pathway, just like many other signaling pathways, is a major target for medicative interference. I therefore at first studied the subcellular distribution of Smad1, which is the main signal transducing protein of the BMP signaling pathway, in a quantitative manner and in response to various types and levels of stimuli in murine c2c12 cells. Results indicate that the subcellular localization of Smad1 is not dependent on the initial BMP input. Surprisingly, only the phospho-Smad1 level is proportionally associated to ligand concentration. Furthermore, the activated transducer proteins were entirely located in the nucleus. Besides the subcellular localization of Smad1, I have analyzed the gene expression profile induced by BMP signaling. Therefore, I examined two endogenous immediate early BMP targets as well as the expression of the stably transgenic Gaussia Luciferase. Interestingly, the results of these independent experimental setups and read-outs suggest oscillating target gene expression. The amplitudes of the oscillations showed a precise concentration-dependence for continuous and transient stimulation. Additionally, even short-time stimulation of 15' activates oscillating gene-expression pulses that are detectable for at least 30h post-stimulation. Only treatment with a BMP type I receptor kinase inhibitor leads to the complete abolishment of the target gene expression. This indicated that target gene expression oscillations depend directly on BMP type I receptor kinase activity.},
  subject      = {Knochen-Morphogenese-Proteine},
  language  = {en}
}
@article{JacklSebald1974,
  author    = {Jackl, G. and Sebald, Walter},
  title     = {Identification of two products of mitochondrial protein synthesis associated with oligomycin-sensitive ATPase from Neurospora crassa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82093},
  year      = {1974},
  abstract  = {no abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{WeissSebald1978,
  author    = {Weiss, H. and Sebald, Walter},
  title     = {Purification of cytochrome oxidase from Neurospora crassa and other sources},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82082},
  year      = {1978},
  abstract  = {A chromatographic procedure 1 is described by means of which cytochrome oxidase has been purified from a variety of organisms including the fungus N eurospora crassa,2,3 the unicellular alga Po/ytoma mirum, 4 the insect Locusta migratoria ,5 the frog Xenopus muel/eri,4 and the mammal Rattus norwegicus. 4 This procedure can be used to equal effect for large-scale preparations, starting from grams of mitochondrial protein, or for small-scale preparations starting from milligrams. The cytochrome oxidase preparations from the different organisms are enzymically active. They show similar subunit compositions.},
  subject      = {Biochemie},
  language  = {en}
}
@article{SebaldNeupertWeiss1979,
  author    = {Sebald, Walter and Neupert, W. and Weiss, H.},
  title     = {Preparation of Neurospora crassa mitochondria},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82070},
  year      = {1979},
  abstract  = {The fungus Neurospora crassa represents a eukaryotic cell with high biosynthetic activities. Cell mass doubles in 2-4 hr during expone ntial growth , even in simple salt media with sucrose as the sole carbon source. The microorgani sm forms a mycelium of long hyphae durlng vegetative growth . The mitochondria can be isolated under relatively gentle condi tions since a few breaks in the threadlike hyphae are sufficient to cause the outflow of the organelles. This article describes two methods for the physical disruption of the hyphae : (I) The cell s are opened in a grind mill between two rotating corundum di sks. This is a continuous and fast procedure and allows large- and small-scale preparations of mitochondria. (2) Hyphae are ground with sand in a mortar and pestle. This procedure can be applied to microscale preparations of mitochondria starting with minute amounts of cells. Other procedures for the isolation of Neurospora mitochondria after the physical di sruption or the enzymatic degradation of the cell wall have been described elsewhere},
  subject      = {Biochemie},
  language  = {en}
}
@article{SebaldWild1979,
  author    = {Sebald, Walter and Wild, G.},
  title     = {Mitochondrial ATPase complex from Neurospora crassa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82065},
  year      = {1979},
  abstract  = {The A TPase eomplex has been isolated from mitoehondria of N eurospora crassa by immunologieal teehniques. The protein ean be obtained rapidly and qua ntitatively in high purity by miero- or large-seale immunopreeipitation. Immunopreeipitation has been applied to labeled and doubly labeled mitoehondrial proteins in order to investigate the number and moleeular weights of subunit polypeptides , the site of synthesis of subunit polypeptides, and the dieycIohexyIcarbodiimide-binding protein . The A TPase complex obtained by large-seale immunopreeipitation has been used as starting ma terial for the isolation of hydrophobie polypeptides.},
  subject      = {Biochemie},
  language  = {en}
}
@article{SebaldWernerWeiss1979,
  author    = {Sebald, Walter and Werner, S and Weiss, H},
  title     = {Biogenesis of mitochondrial membrane proteins in Neurospora crassa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82055},
  year      = {1979},
  abstract  = {no abstract available},
  subject      = {Biochemie},
  language  = {en}
}
@article{WernerSebald1981,
  author    = {Werner, S. and Sebald, Werner},
  title     = {Immunological techniques for studies on the biogenesis of mitochondrial membrane proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82044},
  year      = {1981},
  abstract  = {no abstract available},
  subject      = {Biochemie},
  language  = {en}
}
@article{ViebrockPerzSebald1983,
  author    = {Viebrock, A and Perz, A and Sebald, Walter},
  title     = {Molecular cloning of middle-abundant mRNAs from Neurospora crassa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82033},
  year      = {1983},
  abstract  = {no abstract available},
  subject      = {Neurospora crassa},
  language  = {en}
}
@article{HoppeSebald1984,
  author    = {Hoppe, J. and Sebald, Walter},
  title     = {The proton conducting F0-part of bacterial ATP synthases},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-82019},
  year      = {1984},
  abstract  = {No abstract available},
  subject      = {Biologie},
  language  = {en}
}
@article{Scheer1994,
  author    = {Scheer, Ulrich},
  title     = {Harold Garnet Callan 1917-1993},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80789},
  year      = {1994},
  abstract  = {Professor Harold Gamet Callan, honorary member of the German Society for Cell Biology, died on the 3rd November 1993, at the age of 76. His name is inseparably connected with lampbrush chromosomes, the most spectacular and aesthetically ailuring form of chromosomes, which occupied the major part of his scientific career. " Mick" Callan's pioneering studies led to fruitful new concepts, served as a building block for many subsequent studies by others, and contributed enormously to our current understanding of chromosome organization and activity ...},
  subject      = {Harold Garnet Callan},
  language  = {en}
}
@article{AndersSchartlBarnekowetal.1984,
  author    = {Anders, F. and Schartl., Manfred and Barnekow, A. and Anders, A.},
  title     = {Xiphophorus as an in vivo model for studies on normal and defective control of oncogenes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80721},
  year      = {1984},
  abstract  = {The Xiphophorus tumor system has provided the opportunity to reduce the enormous complexity of cancer etiology to a few biological elements basically involved in neoplasia. The development of a tumor requires an oncogene which, after impairment, deletion, or elimination of its regulatory genes is permitted to mediate neoplastic transformation. Emphasis is being placed today in cancer research on the actual oncogenes themselves, but, in our opinion, the most important genes involved in neoplasia are these regulatory genes. However, although detected by c1assical genetics in the Xiphophorus system, th ese genes are not at present open to a more fin ely detailed molecular biological analysis. Their actual mode of action is therefore still far from being understood.},
  subject      = {Xiphophorus},
  language  = {en}
}
@article{MalitschekSchartl1991,
  author    = {Malitschek, B. and Schartl, Manfred},
  title     = {Rapid identification of recombinant baculoviruses using PCR},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80328},
  year      = {1991},
  abstract  = {no abstract available},
  subject      = {PCR},
  language  = {en}
}
@article{SchluppParzefallSchartl1991,
  author    = {Schlupp, I. and Parzefall, J. and Schartl, Manfred},
  title     = {Male mate choice in mixed bisexual/-unisexual breeding complexes of Poecilia (Teleostei: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80309},
  year      = {1991},
  abstract  = {The livebearing all-female fish Poecilia formosa reproduces by gynogenesis, a modified form of parthenogenesis. P. formosa forms at least two breeding complexes: in its northern range it exists sympatrically with Poecilia latipinna and in its southern range with Poecilia mexicana. Differences between these complexes and their possible origin are discussed. Embryogenesis is triggered by sperm of males of these closely related sympatric species. Because inheritance is stricdy maternal, from the male point of view energy and time invested are totally lost. In this study we wanted to elucidate whether males are able to distinguish between conspecific and parasitic females. It could be shown that males are able to distinguish females optically, but that this ability was obscured as soon as chemical and/or tactile contact was possible. Furthermore, we found that females in an attractive phase of their sexual cycle are always preferred, regardless of species. This is possibly the mechanism by which parasitic females obtain the matings they need to reproduce.},
  subject      = {Poecilia (Teleostei: Poeciliidae)},
  language  = {en}
}
@article{OttilieRaulfBarnekowetal.1992,
  author    = {Ottilie, S. and Raulf, F. and Barnekow, A. and Hannig, G. and Schartl, Manfred},
  title     = {Multiple src-related kinase genes, srk1-4, in the fresh water sponge Spongilla lacustris},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80282},
  year      = {1992},
  abstract  = {In one of the simplest metazoan organisms, the sponge Spongilla lacustris, at least four different src-related kin ase genes (srkl-4) are expressed, aD of which show a high degree of similarity to the c-src genes of vertebrates. Whereas srk2 and srk3 are c1early unrelated at the nucleic acid level, srkl and srk4 share identical sequences in the 5' parts of their cDNAs. The cloning of several primer extension clones and genomic polymerase chain re action experiments confirmed the hypo thesis of an alternative splicing of tandemly arranged carboxyterminal parts of srkl and srk4. The genomic sequence encoding both proteins was found to be interrupted at the splice point by an intron which is located in the same position as one of the introns in the chicken src gene, which is the only gene conserved in invertebrates and vertebrates. All four srk genes are expressed in adult sponges as mRNA transcripts of about 2.2 kb. Tyrosine kin ase activity of a src-related kin ase could be detected in adult sponges but not in their resting form (gemmulae), and may reflect the activity of the srk protein products. Spongilla lacustris is the simplest organism from which a pro tein tyrosine kinase gene has been isolated. The presence of at least four such genes in the evolutionary ancient and primitive phylum Porifera suggests that tyrosine kinase genes arose concomitantly with or shortly after the appearance of multicellular organisms and that their activity may be involved in aggregation and cell-cell recognition.},
  subject      = {Spongilla lacustris},
  language  = {en}
}
@phdthesis{Chen2012,
  author    = {Chen, Yi-chun},
  title     = {Experimental access to the content of an olfactory memory trace in larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83705},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Animals need to evaluate their experiences in order to cope with new situations they encounter. This requires the ability of learning and memory. Drosophila melanogaster lends itself as an animal model for such research because elaborate genetic techniques are available. Drosphila larva even saves cellular redundancy in parts of its nervous system. My Thesis has two parts dealing with associative olfactory learning in larval Drosophila. Firstly, I tackle the question of odour processing in respect to odour quality and intensity. Secondly, by focusing on the evolutionarily conserved presynaptic protein Synapsin, olfactory learning on the cellular and molecular level is investigated. Part I.1. provides a behaviour-based estimate of odour similarity in larval Drosophila by using four recognition-type experiments to result in a combined, task-independent estimate of perceived difference between odour-pairs. A further comparison of these combined perceived differences to published calculations of physico-chemical difference reveals a weak correlation between perceptual and physico-chemical similarity. Part I.2. focuses on how odour intensity is interpreted in the process of olfactory learning in larval Drosophila. First, the dose-effect curves of learnability across odour intensities are described in order to choose odour intensities such that larvae are trained at intermediate odour intensity, but tested for retention either with that trained intermediate odour intensity, or with respectively HIGHer or LOWer intensities. A specificity of retention for the trained intensity is observed for all the odours used. Such intensity specificity of learning adds to appreciate the richness in 'content' of olfactory memory traces, and to define the demands on computational models of associative olfactory memory trace formation. In part II.1. of the thesis, the cellular site and molecular mode of Synapsin function is investigated- an evolutionarily conserved, presynaptic vesicular phosphoprotein. On the cellular level, the study shows a Synapsin-dependent memory trace in the mushroom bodies, a third-order "cortical" brain region of the insects; on the molecular level, Synapsin engages as a downstream element of the AC-cAMP-PKA signalling cascade.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Devine2013,
  author    = {Devine, Eric},
  title     = {Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83583},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {A large number of metabolic waste products accumulate in the blood of patients with renal failure. Since these solutes have deleterious effects on the biological functions, they are called uremic toxins and have been classified in three groups: 1) small water soluble solutes (MW < 500 Da), 2) small solutes with known protein binding (MW < 500 Da), and 3) middle molecules (500 Da < MW < 60 kDa). Protein bound uremic toxins are poorly removed by conventional hemodialysis treatments because of their high protein binding and high distribution volume. The prototypical protein bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are associated with the progression of chronic kidney disease, cardiovascular outcomes, and mortality of patients on maintenance hemodialysis. Furthermore, these two compounds are bound to albumin, the main plasma protein, via electrostatic and/or Van-der-Waals forces. The aim of the present thesis was to develop a dialysis strategy, based on the reversible modification of the ionic strength in the blood stream by increasing the sodium chloride (NaCl) concentration, in order to enhance the removal of protein bound substances, such as IS and pCS, with the ultimate goal to improve clinical patient outcomes. Enhancing the NaCl concentration ([NaCl]) in both human normal and uremic plasma was efficient to reduce the protein bound fraction of both IS and pCS by reducing their binding affinity to albumin. Increasing the ionic strength was feasible during modified pre-dilution hemodiafiltration (HDF) by increasing the [NaCl] in the substitution fluid. The NaCl excess was adequately removed within the hemodialyzer. This method was effective to increase the removal rate of both protein bound uremic toxins. Its ex vivo hemocompatibility, however, was limited by the osmotic shock induced by the high [NaCl] in the substituate. Therefore, modified pre-dilution HDF was further iterated by introducing a second serial cartridge, named the serial dialyzers (SDial) setup. This setting was validated for feasibility, hemocompatibility, and toxin removal efficiency. A better hemocompatibility at similar efficacy was obtained with the SDial setup compared with the modified pre-dilution HDF. Both methods were finally tested in an animal sheep model of dialysis to verify biocompatibility. Low hemolysis and no activation of both the complement and the coagulation systems were observed when increasing the [NaCl] in blood up to 0.45 and 0.60 M with the modified pre-dilution HDF and the SDial setup, respectively. In conclusion, the two dialysis methods developed to transitory enhance the ionic strength in blood demonstrated adequate biocompatibility and improved the removal of protein bound uremic toxins by decreasing their protein bound fraction. The concepts require follow-on clinical trials to assess their in vivo efficacy and their impact on long-term clinical outcomes.},
  subject      = {H{\"a}modiafiltration},
  language  = {en}
}
@phdthesis{Link2013,
  author    = {Link, Jana},
  title     = {The role of meiotic nuclear envelope components in chromosome dynamics and meiotic progression},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83540},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Meiosis is the specialised cell division which produces haploid germ cells, capable of developing into fertile gametes, from diploid progenitor cells. During meiosis, chromosomes undergo strictly regulated and strongly conserved dynamic processes, at the beginning of which the telomeres are actively tethered and intimately attached to the nuclear envelope (NE). The attached telomeres are then moved within the NE through cytoskeletal forces to cluster within a restricted region, forming the highly conserved bouquet stage. Subsequently, the bouquet is released simultaneously to the completion of the synaptonemal complex assembly tightly linking homologous chromosome pairs together. In combination these processes are essential for the successful completion of meiosis. Because the meiotic NE serves as a platform for telomere attachment and movement it can be assumed to be critically involved in these events crucial for fertility. However, the precise roles of many meiotic NE proteins in the attachment and movement of telomeres still remain elusive. Therefore, it was the aim of this thesis to investigate the functions of two mammalian meiotic NE components in telomere attachment and dynamics. The first part of this thesis is concerned with the meiosis-specific lamin C2. Lamin C2 is the only A-type lamin expressed during meiosis and has in previous studies shown to feature altered meiosis-specific properties, clearly distinguishing it from somatic lamins. Because lamin C2 is enriched at sites of telomere attachment, exhibits a high mobility within the nuclear lamina and influences NE integrity, it has been postulated that it may locally increase NE flexibility to allow efficient meiotic telomere movement. Therefore, possible functions of lamin C2 in the movement of attached telomeres were investigated in this thesis by studying the bouquet formation and release of pubertal mice specifically lacking lamin C2. This revealed that lamin C2 deficient mice show a delayed bouquet release, leading to severe defects in the synaptic pairing of homologous chromosomes, which in turn results in infertility of the males. Therefore, the efficient repositioning of attached meiotic telomeres, facilitated by lamin C2, seems essential for completing meiosis. The second part of this thesis focuses on the protein complex responsible for the attachment of meiotic telomeres to the NE and their coupling to the cytoskeleton. The so-called LINC complex is composed of SUN domain proteins in the inner nuclear membrane interacting with KASH domain proteins of the outer nuclear membrane. In previous studies it had been shown that SUN1, SUN2 and KASH5 localise to the attached meiotic telomeres. Regarding the meiotic role of SUN2, however, contradicting results have recently been discussed, showing the need for further investigations. Using an available SUN1 deficient mouse strain, this thesis was able to show that SUN2 is sufficient for telomere attachment per se although telomere attachment is impaired in SUN1 deficient mice leading to infertility. It is also demonstrated that SUN2 forms a functional LINC complex together with KASH5 to mediate this telomere attachment. This LINC complex in the absence of SUN1 is able to move attached telomeres into a bouquet-like cluster formation. Therefore, this demonstrates that SUN2 is involved in the functional attachment and movement of meiotic telomeres. In summary, this thesis has shown SUN2 and the meiotic nuclear lamina to be directly involved in or essential for the highly conserved attachment and movement of telomeres, making them critical for a successful meiosis. The meiotic NE is therefore in this thesis demonstrated to be a determinant of mammalian fertility.},
  subject      = {Meiose},
  language  = {en}
}
@phdthesis{Schleyer2012,
  author    = {Schleyer, Michael},
  title     = {Integrating past, present and future: mechanisms of a simple decision in larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78923},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Is behaviour response or action? In this Thesis I study this question regarding a rather simple organism, the larva of the fruit fly Drosophila melanogaster. Despite its numerically simple brain and limited behavioural repertoire, it is nevertheless capable to accomplish surprisingly complex tasks. After association of an odour and a rewarding or punishing reinforcement signal, the learnt odour is able to retrieve the formed memory trace. However, the activated memory trace is not automatically turned into learned behaviour: Appetitive memory traces are behaviourally expressed only in absence of the rewarding tastant whereas aversive memory traces are behaviourally expressed in the presence of the punishing tastant. The 'decision' whether to behaviourally express a memory trace or not relies on a quantitive comparison between memory trace and current situation: only if the memory trace (after odour-sugar training) predicts a stronger sugar reward than currently present, animals show appetitive conditioned behaviour. Learned appetitive behaviour is best seen as active search for food - being pointless in the presence of (enough) food. Learned aversive behaviour, in turn, can be seen as escape from a punishment - being pointless in absence of punishment. Importantly, appetitive and aversive memory traces can be formed and retrieved independent from each other but also can, under appriate circumstances, summate to jointly organise conditioned behaviour. In contrast to learned behaviour, innate olfactory behaviour is not influenced by gustatory processing and vice versa. Thus, innate olfactory and gustatory behaviour is rather rigid and reflexive in nature, being executed almost regardless of other environmental cues. I suggest a behavioural circuit-model of chemosensory behaviour and the 'decision' process whether to behaviourally express a memory trace or not. This model reflects known components of the larval chemobehavioural circuit and provides clear hypotheses about the kinds of architecture to look for in the currently unknown parts of this circuit. The second chapter deals with gustatory perception and processing (especially of bitter substances). Quinine, the bitter tastant in tonic water and bitter lemon, is aversive for larvae, suppresses feeding behaviour and can act as aversive reinforcer in learning experiments. However, all three examined behaviours differ in their dose-effect dynamics, suggesting different molecular and cellular processing streams at some level. Innate choice behaviour, thought to be relatively reflexive and hard-wired, nevertheless can be influenced by the gustatory context. That is, attraction toward sweet tastants is decreased in presence of bitter tastants. The extent of this inhibitory effect depends on the concentration of both sweet and bitter tastant. Importantly, sweet tastants differ in their sensitivity to bitter interference, indicating a stimulus-specific mechanism. The molecular and cellular processes underlying the inhibitory effect of bitter tastants are unknown, but the behavioural results presented here provide a framework to further investigate interactions of gustatory processing streams.},
  subject      = {Lernen},
  language  = {en}
}