The transmission of sex pheromone-mediated signals is essential for goldfish reproduction. However, the neural pathways underlying this reproductive signalling pathway in the goldfish brain is not well described. Lesioning experiments have shown previously that two brain areas, the preoptic area (POA) and the ventral telencephali pars ventralis (Vv) in particular, are important for reproduction. We used patch clamp electrophysiology to study the electrical activities of POA and Vv neurons. Based on the intrinsic properties of these neurons, we suggest there are five different functional classes of POA neurons and a single class of Vv neurons. In addition, by electrically stimulating the olfactory bulb (OB), we were able to show that this primary sensory structure makes monosynaptic glutamatergic connections with both POA and Vv neurons. While electrophysiology measures signalling events occurring at short time scales on the order of milliseconds to minutes, we were also interested in studying sex pheromone signalling in the goldfish brain over a long time scale. Thus, we describe changes in gene expression in male goldfish exposed to waterborne sex pheromones (17alpha,20beta dihydroxy-4-pregene-3-one and Prostaglandin-F2alpha) over 6 hours. We perform cDNA microarrays on Prostaglandin-F2alpha-treated fish to study the rapid modulation of transcription and define the signalling pathways affected. Our microarrays showed that 71 genes were differentially regulated (67 up and 4 down). Through gene ontology enrichment analysis, we found that these genes were involved in various biological processes such as RNA processing, neurotransmission, neuronal development, apoptosis, cellular metabolism and sexual reproduction. RT-PCRs were performed to validate our microarrays and to facilitate direct comparisons of the effects of the two sex pheromones, 17alpha,20beta dihydroxy-4-pregene-3-one and Prostaglandin-F2alpha. By combining electrophysiology and gene expression analyses, we were able to study sex-pheromone signalling on two different time scales. One short, occurring on the order of milliseconds to minutes, that involves electrical activities in the brain through the glutamatergic amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-D-aspartate receptors; and the other long occurring several hours later that involves changes in the gene expression levels of calmodulin and ependymin among other genes underlying neuroplasticity. Reproductive neuroplasticity in the goldfish may therefore require the activation of glutamatergic receptors which then activate downstream signals like calmodulin and ependymin to transform the sex pheromones-mediate signal into gene expression.

Le récepteur aux cannabinoïdes de type 1 (CB1) est un récepteur couplé aux protéines G, abondamment exprimé dans le cerveau et régulant plusieurs processus physiologiques. Cependant, les mécanismes cellulaires par lesquels les CB1 régulent ces processus n’ont été que peu analysés. Bien que les CB1 localisés dans les membranes plasmiques sont connus pour induire la transduction de signal; une partie de ces récepteurs sont aussi fonctionnels au niveau des mitochondries (mtCB1), où leur stimulation réduit la respiration mitochondriale. L’objectif de cette thèse fut d’évaluer l’impact de l’activation des récepteurs mtCB1 du cerveau sur les effets connus des cannabinoïdes. Afin de distinguer la fonction des mtCB1 de celle des autres populations de récepteurs, nous avons développé des outils basés sur la signalisation induite par les mtCB1. Dans les mitochondries isolées de cerveau, l’activation des protéines Gαi/o, dépendante des mtCB1 diminue l’activité de l’adénylyl cyclase soluble (sAC). L'inhibition locale de l’activité de sAC prévient l’amnésie, la catalepsie et partiellement l’hypolocomotion induite par les cannabinoïdes. De plus, nous avons généré une protéine fonctionnelle mutante CB1 (DN22-CB1) dépourvue des 22 premiers acides aminés des CB1 ainsi que de sa localisation mitochondriale. Contrairement aux CB1, l'activation des DN22-CB1 n’affecte pas l'activité mitochondriale. Enfin, l’expression des DN22-CB1 dans l’hippocampe bloque à la fois la diminution de la transmission synaptique et l’amnésie induites par les cannabinoïdes. Ces travaux démontrent l’implication des mtCB1 dans certains effets des cannabinoïdes et le rôle clé des processus bioénergétiques contrôlant les fonctions cérébrales. / Type-1 cannabinoid receptor CB1 is a G protein-coupled receptor (GPCR), widely expressed in the brain, which regulates numerous physiological processes. However, the cellular mechanisms of CB1-mediated control of these functions are poorly understood. Although CB1 are known to signal at the plasma membrane, a portion of these receptors are also present in mitochondria (mtCB1), where mtCB1 activation decreases mitochondrial activity. The goal of this thesis was to dissect the impact of brain mtCB1 signaling in known behavioral effects induced by cannabinoids. To distinguish the functions of mtCB1 from other receptor pools, we developed tools based on the characterization of the intra-mitochondrial molecular cascade induced by mtCB1 receptors. In isolated brain mitochondria, we found that intra-mitochondrial decrease of soluble-adenylyl cyclase (sAC) activity links mtCB1- dependent activation of Gαi/o proteins to decrease cellular respiration. Local brain inhibition of sAC activity blocks cannabinoid-induced amnesia, catalepsy and contributes to the hypolocomotor effect of cannabinoids. In addition, we generated a functional mutant CB1 protein (DN22-CB1) lacking the first 22 amino acid of CB1 and its mitochondrial localization. Differently from CB1, activation of DN22-CB1 does not affect mitochondrial activity. Hippocampal in vivo expression of DN22-CB1 abolished both cannabinoid-induced impairment of synaptic transmission and amnesia in mice. Together, these studies couple mitochondrial activity to behavioral performances. The involvement of mtCB1 in the effects of cannabinoids on memory and motor control highlights the key role of bioenergetic processes as regulators of brain functions.

Als Folge der seit Ende der 1960er Jahre gestiegenen Auslandsverschuldung avancierte der Export der DDR in das NSW zur Schicksalsfrage. Zu den ausfuhrintensivsten, Finalerzeugnisse herstellenden Branchen, mit einem kontinuierlichen Absatz im NSW zählte, neben dem Druckmaschinenbau vor allem der Werkzeugmaschinenbau. Zu beiden Branchen fehlen bislang dementsprechende Untersuchungen. Die vorliegende Arbeit schließt also eine Forschungslücke! Zwei Dinge waren entscheidend für den im Gegensatz zu anderen Branchen der DDR kontinuierlichen Absatz von Werkzeugmaschinen in das NSW: Erstens der Wille der DDR, Geschäfte in Form von Ware gegen Waren zu tätigen, um auf diese Weise Devisen zu sparen. Zweitens politische Aspekte. Weiterhin war es möglich den DDR-Werkzeugmaschinenbau in die weltweite Entwicklung des Werkzeugmaschinenbaus einzuordnen. Zur globalen Einordnung kommt diejenige auf den jeweiligen nationalen Märkten. Während Betrachtungen zur Wirtschaft der DDR gemeinhin von einer pauschalen Wettbewerbsschwäche der Wirtschaft der DDR sprechen, ohne die branchenspezifischen Probleme genauer zu betrachten, differenziert die vorliegende Arbeit stärker nach einzelnen Ursachen. Erstens die seit 1973 in immer kürzeren Abständen auftretenden zyklischen Wirtschaftskrisen, die der metallverarbeitenden Industrie, besonders der zivilen, schwer zusetzten. Bis schließlich im Jahr 1982 die Märkte im NSW beinahe vollständig zusammenbrachen, was sowohl zu einer verschärften Preispolitik als auch zur Abschottung der nationalen Märkte mittels Protektionismus führte. Zweitens technische und qualitative Probleme. Dazu gehörten neben der nicht wettbewerbsfähigen Elektrik vor allem die nicht konkurrenzfähigen mikroelektronischen Steuerungen. Drittens scheiterten auch die in den, im Vergleich zur westeuropäischen Konkurrenz ohnehin zu spät generierten Anlagenexport, gesetzten Hoffnungen. Sowohl der Irak als auch die Türkei, als die beiden größten Abnehmer von Anlagen, gerieten, wenn auch aus unterschiedlichen Gründen, in immer schwierigeres Fahrwasser. / As a consequence of the growing foreign indebtedness since the late 1960s, the export of the German Democratic Republik (GDR) into the western markets became a question of to be or not to be. One of the most competitive sector of industry, producing final industrial goods, was, beside printing machine industry, the east german machine tool industry. Researches about their exports are still missing until today. That means the present work closes a gap of research! Two things were decisive for a continuously sale of east german machine tools into the western markets: First the will of the GDR to deal wares against wares to save foreign currencies. The international competition of the east german machine tools was a precondition to be used as an exchange currency. Seconds political reasons. Furthermor it was possible to put the east german machine tool industry in its worldwide proper place. Beside the worldwide comparison it was possible to analyse the national marketparts of the GDRs machine tool industry. While views on the east german economy talk about a lack of competition in general, without looking at the specific problems of the respective industry branch the present work distinguishes between single reasons: First the shorter intervals of the economical crises since 1973 that caused damages especially in the civil metal processing. In 1982 the western markets nearly went in totally decline, what caused an aggravate prize policy an d the closing of the national markets by protctionism. Second technical an qualitative problems. Third the too late generated export of plants connected with economical troubles of the two main importers, Iraq and Turkey.

Title: The subnuclear localisation of Notch responsive genes. Candidate Name: Matthew Jones Notch signalling is a highly conserved cell-cell communication pathway with critical roles in metazoan development and mutations in Notch pathway components are implicated in many types of cancer. Notch is an excellent and well-studied model of biological signalling and gene regulation, with a single intracellular messenger, one receptor and two ligands in Drosophila. However, despite the limited number of chemical players involved, a striking number of different outcomes arise. Molecular studies have shown that Notch activates different targets in different cell types and it is well known that Notch is important for maintaining a stem cell fate in some situations and driving differentiation in others. Thus some of the factors affecting the regulation of Notch target genes are yet to be discovered. Previous studies in various organisms have found that the location of a gene within the nucleus is important for its regulation and genome reorganisation can occur following gene activation or during development. Therefore this project aimed to label individual Notch responsive loci and determine their subnuclear localisation. In order to tag loci of interest a CRISPR/Cas9 genome-editing method was established that enabled the insertion of locus tags at Notch targets, namely the well-characterized Enhancer of split locus and also dpn and Hey, two transcription factors involved in neural cell fate decisions. The ParB/Int system is a recently developed locus tagging system and is not well characterised in Drosophila. It has a number of advantages over the traditional LacO/LacI-GFP locus tagging system as it does not rely on binding site repeats for signal amplification and can label two loci simultaneously in different colours. This thesis characterised the ParB/Int system in the Drosophila salivary gland and larval L3 neuroblast. Using 3D image segmentation hundreds of nuclei were reconstructed and a volume based normalisation method was applied to determine the subnuclear localisation of several Notch targets with and without genetic manipulations of the Notch pathway.

This dissertation deals with the interpretation of four myths from early medieval Scandinavia, in which the main role is played by the god Óðinn. All four myths narrate how he achieved a state of permanent increase of his numinous knowledge. Based on the fact that the outcome of all of the narratives is the acquisition of the Mead of Poetry (or its equivalent), they can be percieved as "four reports on the same event". The analysis of myths itself has been executed in two steps: firstly the separate inquiry of the two more central myths and introduction of the other two followed by thorough analysis of the four together. All four myths demonstrate to a certain degree a presence of motifs and structures associated with the religious phenomena of sacrifice and initiation. By the means of said analysis the study reviews the systematic relations of the sacrificial and initiatory structures and postulates a common core which is subsequently named "monomyth".

Als Folge der seit Ende der 1960er Jahre gestiegenen Auslandsverschuldung avancierte der Export der DDR in das NSW zur Schicksalsfrage. Zu den ausfuhrintensivsten, Finalerzeugnisse herstellenden Branchen, mit einem kontinuierlichen Absatz im NSW zählte, neben dem Druckmaschinenbau vor allem der Werkzeugmaschinenbau. Zu beiden Branchen fehlen bislang dementsprechende Untersuchungen. Die vorliegende Arbeit schließt also eine Forschungslücke! Zwei Dinge waren entscheidend für den im Gegensatz zu anderen Branchen der DDR kontinuierlichen Absatz von Werkzeugmaschinen in das NSW: Erstens der Wille der DDR, Geschäfte in Form von Ware gegen Waren zu tätigen, um auf diese Weise Devisen zu sparen. Zweitens politische Aspekte. Weiterhin war es möglich den DDR-Werkzeugmaschinenbau in die weltweite Entwicklung des Werkzeugmaschinenbaus einzuordnen. Zur globalen Einordnung kommt diejenige auf den jeweiligen nationalen Märkten. Während Betrachtungen zur Wirtschaft der DDR gemeinhin von einer pauschalen Wettbewerbsschwäche der Wirtschaft der DDR sprechen, ohne die branchenspezifischen Probleme genauer zu betrachten, differenziert die vorliegende Arbeit stärker nach einzelnen Ursachen. Erstens die seit 1973 in immer kürzeren Abständen auftretenden zyklischen Wirtschaftskrisen, die der metallverarbeitenden Industrie, besonders der zivilen, schwer zusetzten. Bis schließlich im Jahr 1982 die Märkte im NSW beinahe vollständig zusammenbrachen, was sowohl zu einer verschärften Preispolitik als auch zur Abschottung der nationalen Märkte mittels Protektionismus führte. Zweitens technische und qualitative Probleme. Dazu gehörten neben der nicht wettbewerbsfähigen Elektrik vor allem die nicht konkurrenzfähigen mikroelektronischen Steuerungen. Drittens scheiterten auch die in den, im Vergleich zur westeuropäischen Konkurrenz ohnehin zu spät generierten Anlagenexport, gesetzten Hoffnungen. Sowohl der Irak als auch die Türkei, als die beiden größten Abnehmer von Anlagen, gerieten, wenn auch aus unterschiedlichen Gründen, in immer schwierigeres Fahrwasser. / As a consequence of the growing foreign indebtedness since the late 1960s, the export of the German Democratic Republik (GDR) into the western markets became a question of to be or not to be. One of the most competitive sector of industry, producing final industrial goods, was, beside printing machine industry, the east german machine tool industry. Researches about their exports are still missing until today. That means the present work closes a gap of research! Two things were decisive for a continuously sale of east german machine tools into the western markets: First the will of the GDR to deal wares against wares to save foreign currencies. The international competition of the east german machine tools was a precondition to be used as an exchange currency. Seconds political reasons. Furthermor it was possible to put the east german machine tool industry in its worldwide proper place. Beside the worldwide comparison it was possible to analyse the national marketparts of the GDRs machine tool industry. While views on the east german economy talk about a lack of competition in general, without looking at the specific problems of the respective industry branch the present work distinguishes between single reasons: First the shorter intervals of the economical crises since 1973 that caused damages especially in the civil metal processing. In 1982 the western markets nearly went in totally decline, what caused an aggravate prize policy an d the closing of the national markets by protctionism. Second technical an qualitative problems. Third the too late generated export of plants connected with economical troubles of the two main importers, Iraq and Turkey.

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