Transcription factors (TFs) are key regulatory proteins that regulate transcriptionthrough precise, but highly variable binding events to cis-regulatory elements.The complexity of their regulatory patterns makes it difficult to determinethe roles of different TFs, a task which the field is still struggling with.Experimental procedures for this purpose, such as knock out experiments, arehowever costly and time consuming, and with the ever-increasing availabilityof sequencing data, computational methods for inferring the activity of TFsfrom such data have become of great interest. Current methods are howeverlacking in several regards, which necessitates further exploration of alternatives. A novel tool for estimating the activity of individual TFs over time fromlongitudinal mRNA expression data was in this project therefore put togetherand tested on data from Mus musculus liver and brain. The tool is based onprincipal component analysis, which is applied to data subsets containing theexpression data of genes likely regulated by a specific TF to acquire an estimationof its activity. Though initial tests on 17 selected TFs showed issues withunspecific trends in the estimations, further testing is required for a statementon the potential of the estimator. / Transcriptionsfaktorer (TFer) är viktiga regulatoriska protein som reglerar transkriptiongenom att binda till cis-regulatoriska element på precisa, menmycketvarierande vis. Komplexiteten i deras regulatoriska mönster gör det svårt attavgöra vilka roller olika TFer har, vilket är en uppgift som fältet fortfarandebrottas med. Experimentella procedurer i detta syfte, till exempel "knockout"experiment, är dock kostsamma och tidskrävande, och med den evigt ökandetillgången på sekvenseringsdata har metoder för att beräkna TFers aktivitetfrån sådan data fått stort intresse. De beräkningsmetoder som finns idag bristerdock på flera punker, vilket erfordrar ett fortsatt sökande efter alternativ. Ett nytt vektyg för att upskatta aktiviteten hos individuella TFer över tidmed hjälp av longitunell mRNA-uttrycksdata utvecklades därför i det här projektetoch testades på data från Mus musculus lever och hjärna. Verktyget ärbaserat på principalkomponentsanalys, som applicerades på set med uttrycksdatafrån gener sannolikt reglerade av en specifik TF för att erhålla en uppskattningav dess aktivitet. Trots att de första testerna för 17 utvalda TFer påvisadeproblem med ospecifika trender i upskattningarna krävs forsatta tester för attkunna ge ett tydligt svar på vilken potential estimatorn har.

The human-abetted introduction of commensal species (i.e. those that opportunistically exploit the anthropogenic environment for food and shelter, e.g. rats, cockroaches etc.) to new areas has occurred throughout history. This has resulted in detrimental ecological changes worldwide but, from a viewpoint of human knowledge, a beneficial corollary of these translocations is that the species in question can be used as proxies to study the movement of the humans who transported them. I reconstruct colonisation histories of three widespread commensal mammalian species in the Western Indian Ocean, the black rat Rattus rattus, house mouse Mus musculus and Asian house shrew Suncus murinus, through phylogeographic studies (the geographic distribution of genetic lineages) of maternally-inherited mitochondrial markers, and zooarchaeological data. The DNA analyses are conducted on samples largely derived from museum specimens collected up to 110 years ago, and from archaeological bones (in the case of rats). I show considerable cryptic diversity in all three species, particularly in mice for which we find a potential major new lineage. Certain lineages within each species predominantly reveal long-distance translocations within the Indian Ocean, but high resolution geographic and genetic clustering is also evident, particularly in Asian house shrews. Phylogeographic structuring of the three species in East Africa and the southern Indian Ocean region (e.g. Madagascar, Reunion, etc.) indicate connections with Arabia, the Middle East, and India in the Islamic period from the first millennium AD, and later European connections during the Age of Exploration. Closer to the origins of the three species (the Indian subcontinent in all cases), range expansions in Eurasia and nearby islands relate to early to mid Holocene human populations, but also with signals of later secondary colonisations. Through ancient DNA studies I found genetic continuity between temporally separated populations of black rats suggesting population persistence, and high levels of diversity in Songo Mnara, a Swahili stonetown in Tanzania. Knowledge of the colonisation history and genetic diversity of an introduced species is essential to understand their resilience in novel landscapes, and to identify pathways of invasion and, by proxy, human trade and exchange networks that facilitated their dispersal. My research contributes significantly to that end for three socially, economically and ecologically important species that are well-established in the Indian Ocean region and beyond.

Title: The influence of skating frequency on muscle tone of musculus triceps surae. Objective: The aim of this master degree thesis is to determine whether and how much influence the frequency and intensity of isotonic load the muscle tone of musculus soleus during skating of a professional ice hockey player. The muscle tone of musculus soleus is the most objectively measured part of musculus triceps surae by myotonometer. Methods: The master degree thesis is divided into the theoretical part, the processed form of research that serves as a basis for investigation in the second, empirical part. Change in muscle tone of musculus soleus was investigated by using myotonometer, which followed after a full physiotherapy examination. It is quantitative research using quasi-experimental study. Measurements were performed on 10 subjects - professional ice hockey players who are fully manage the technique of skating on the ice, before load, after low frequency isotonic load and after high frequency isotonic load. Conclusion: The myotonometric measurements revealed that after low and high frequency isotonic load of skating on ice rink, the muscle tone of musculus soleus is the same or slightly lower than before load. Keywords: Muscle tone, myotonometer, musculus soleus, skating, ice hockey

Title: The influence of skating frequency on muscle tone of musculus triceps surae. Objective: The aim of this master degree thesis is to determine whether and how much influence the frequency and intensity of isotonic load the muscle tone of musculus soleus during skating of a professional ice hockey player. The muscle tone of musculus soleus is the most objectively measured part of musculus triceps surae by myotonometer. Summary: The master degree thesis is divided into the theoretical part, the processed form of research that serves as a basis for investigation in the second, empirical part. Change in muscle tone of musculus soleus will be investigated by using myotonometer, which will follow after a full physiotherapy examination. Measurements will be performed on 10 subjects - professional ice hockey players who are fully manage the technique of skating on the ice, before load, after low frequency isotonic load and after high frequency isotonic load. Conclusion: The myotonometric measurements revealed that after low and high frequency isotonic load of skating on ice rink, the muscle tone of musculus soleus is the same or slightly lower than before load. Keywords: Muscle tone, myotonometer, musculus soleus, skating, ice hockey

Texte remanié de: Dissertation--Fachbereich Ev. Theologie--Universität Hamburg, 1999. / Bibliogr. p. 647-671.

Freie Universiẗat, Diss., 2005--Berlin. / Dateiformat: zip, Dateien im PDF-Format. ERscheinungsjahr an der Haupttitelstelle: 2005.

Neurogenin 2 (Ngn2) is a basic Helix-Loop-Helix (bHLH) transcription factor regulating differentiation and cell cycle exit in the developing brain. By transcriptional upregulation of a cascade of other bHLH factors, neural progenitor cells exit the cell cycle and differentiate towards a neuronal fate. Xenopus laevis Ngn2 (xNgn2) is a short-lived protein, targeted for degradation by the 26S proteasome. I have investigated the stability of Ngn2 mediated by post-translational modifications and structural disorder. Firstly I will describe work focused on ubiquitylation of xNgn2, targeting it for proteasomal degradation. xNgn2 is ubiquitylated on lysines, the recognized site of modification. I will discuss the role of lysines in ubiquitylation and stability of xNgn2. In addition to canonical ubiquitylation on lysines, I describe ubiquitylation of xNgn2 on non-canonical sites, namely its amino-terminal amino group, and cysteine, serine and threonine residues. I show that the ubiquitylation of cysteines in particular exhibits cell cycle dependence and is also observed in mammalian cell lines, resulting in cell cycle-dependent regulation of stability. I will then discuss whether phosphorylation, a regulator of xNgn2 activity, also affects xNgn2 stability. I will provide evidence of cell cycle-dependent phosphorylation of cyclin dependent kinase (cdk) consensus sites affecting the stability of xNgn2. Finally I describe studies on the folding properties of Ngn2 to assess their role in protein stability. xNgn2 associates with DNA and its heterodimeric binding partner xE12 and may interact directly with the cyclin-dependent kinase inhibitor Xic1. I will discuss the role of these interaction partners in xNgn2 stability. xNeuroD, a downstream target of xNgn2, is a related bHLH transcription factor which is stable. Here I describe domain swapping experiments between these two proteins highlighting regions conferring instability on the chimeric protein. Finally I will provide nuclear magnetic resonance (NMR) data looking at the effect of phosphorylation on protein structure in mouse Ngn2 (mNgn2).

The coexistence of humans and rodents lasts from the beginnings of the history of agriculture. Many rodent populations accepted to synanthropic way of life and as commensals accompany human societies until today. In the first study we wanted to find out, how the evolution of non-commensal rodent species, a Cypriot mouse (Mus cypriacus), was influenced by people. This endemic island species evolved on the Cyprus Island without presence of any mammalian competitors or predators. In last 10.000 years humans arrived on the island, bringing several mammalian species, which affected the environment markedly. A black rat (Rattus rattus) is now dominant species there and presumably it is an important competitor for the Cypriot mouse. We supposed that the mice should avoid its odour. Nevertheless the rats odour was preferred by the mouse, probably as an odour of phylogenetically related species. On the contraty, the odour of domestic cat (species, which is also widespread on the island), was avoided. In conclusion, the long-term isolation from mammalian predators did not affect the antipredatory reactions of the Cypriot mouse. Our next study was focuse on changes in behavioural strategies of different populations of mice: the main question was how the commensal way of life affects their exploratory...

Los volcanes son formaciones geológicas que resultan atractivas para los asentamientos humanos debido a la fertilidad de sus suelos y su interés turístico. Pero también son una fuente importante de contaminación natural, debido a los procesos geoquímicos que tienen lugar durante los periodos eruptivos y no eruptivos. Se estima que 44 millones de personas viven a menos de 10 km de un volcán activo y ya se ha demostrado el aumento de incidencia de patologías respiratorias en humanos que habitan estos ambientes. La presente Tesis Doctoral tiene como objetivo valorar los efectos neurotóxicos en el sistema nervioso central de ratones domésticos (Mus musculus) que habitan en ambientes volcánicos activos. La acumulación de mercurio en cerebro y médula espinal de individuos expuestos, la activación de células astrocitarias y microgliales y la producción de citocinas proinflamatorias son los principales resultados de este trabajo de los que se desprende que el sistema nervioso central está afectado por la exposición crónica a estos ambientes.

Die vorliegende Arbeit beschäftigt sich mit der Darstellung der plantaren Sprunggelenksregion des Pferdes im MRT. Das typische Signalverhalten des Musculus interosseus medius im MRT soll mit histologischen und sonographischen Untersuchungen abgeglichen werden. Weiterhin wird mit Hilfe des MRT geprüft, ob der charakteristische Binnenaufbau des Musculus interosseus medius einer Veränderung mit zunehmendem Alter der Tiere unterliegt. 27 Gliedmaßen von 22 orthopädisch gesunden Warmblutpferden im Alter von einem Monat bis 25 Jahren wurden magnetresonanztomographisch untersucht. Die MRT – Untersuchung wurde an einem 0,5 Tesla starken Gerät in fünf Sequenzen und drei Schnittebenen durchgeführt. Vergleichend wurde die plantare Sprunggelenksregion bei 14 Tieren ultrasonographisch dargestellt. Die Darstellung der Binnenstruktur des Musculus interosseus medius im MRT sollte deskriptiv erfasst werden. Nachfolgend wurden die Anteile der verschiedenen Gewebsanteile dieser Struktur alterskorrelierend, statistisch ausgewertet und den Signalintensitäten histologisch Gewebe zugeordnet. Grundsätzlich waren alle Strukturen der plantaren Sprunggelenksregion im MRT darstellbar. Unterschiede konnten abhängig von den Strukturen und deren Verlauf in den verschiedenen Schnittebenen festgestellt werden. Die verwendeten Sequenzen zeichneten sich als geeignet für die Weichteildiagnostik aus. In jeder Sequenz zeigte das gewebstypische Signalverhalten charakteristische Grauwertverteilungen. Signifikant am besten ließ sich der Musculus interosseus medius in transversalen Schnittebenen in protonengewichteter Sequenz abgrenzen. Der Binnenaufbau des Musculus interosseus medius konnte in jeder verwendeten Sequenz nachvollzogen werden. Es war keine signifikant feststellbare Korrelation zwischen dem Alter der Pferde und den prozentual ermittelten Gewebsanteilen nachzuweisen. Sonographisch konnte der Musculus interosseus medius weniger gut abgegrenzt werden, auch die Morphologie war nicht so genau nachzuvollziehen. Zur genauen Beurteilung dieser Struktur ist die MRT – Untersuchung der Sonographie überlegen. Den unterschiedlichen Signalverhalten des Musculus interosseus medius konnten histologisch verschiedene Gewebe zugeordnet werden. Dabei handelte es sich um größere Ansammlungen von Fett- und Muskelzellen, die in das sehnige Grundgewebe eingelagert waren. Die Magnetresonanztomographie hat sich als sehr geeignetes Verfahren erwiesen, die Weichteilgewebe der plantaren Sprunggelenksregion des Pferdes gut abgrenzbar darzustellen. Im histologischen Vergleich konnte der Magnetresonanztomographie eine sehr gute Sensitivität und Spezifität nachgewiesen werden.