In dieser retrospektiven Pilotstudie zum Einsatz von rekombinatem, aktivierten Faktor VII bei Frühgeborenen (Schwangerschaftswoche < 32, Geburtsgewicht < 1750 g) mit intraventrikulären Hirnblutungen wurden anhand sonografischer Untersuchungen der Blutungsprogress sowie die Nebenwirkungen der Therapie im Vergleich zur Standarttherapie mit Fresh Frozen Plasma untersucht. Die Auswertung erfolgte in zwei Gruppen: innerhalb des Gesamtkollektives und innerhalb der Matching-Gruppe. Es zeigte sich in beiden Auswertungsgruppen ein signifikant geringerer Blutungsprogress in der Therapiegruppe. Außerdem konnte ein früherer Blutungsstopp in der Therapiegruppe nachgewiesen werden. Ein erhöhtes Nebenwirkungspotential von rekombinantem, aktivierten Faktor VII war in diesem Patientenkollektiv nicht eruierbar. Weiterführende prospektive, randomisierte, multizentische Studien zur Evaluation dieses vielversprechenden Therapieansatzes werden empfohlen.

Recombinant preparation of TEAD transcription factor (abstract) The TEAD family transcription factors play an important role during devolopment of organisms, where their main purpose is to regulate organ size by activating expression of proteins involved in cell growth and differentiation and apoptosis inhibition. TEAD proteins activity is regulated by signalling pathways and interactions with coactivators. Disregulation of these mechanisms can lead to development of tumors, which is the reason why TEAD proteins became an interesting target for development of new anticancer drugs based on inhibiting their activity. There are several possibilities how to inhibit activity of a transcription factor including blocking its bond to DNA. To design a new drug that blocks transcription factors binding to DNA the structural basis of interaction of these two molecules has to be known first. In this thesis the DNA binding domain of human protein TEAD1 was prepared using the technique of recombinant expression in bacteria E. coli. Suitable conditions of protein production were found and the DNA binding domain of TEAD1 protein was purified so it will be possible to use it for structural analysis of its intraction with DNA.

The variety of bacteria and their genomes sometimes causes conservation of homologue molecules to be displayed not in sequence but in secondary and tertiary structures. In the case of the regulatory 6S RNA, sequence homologues have been found in over 100 bacterial species so far. However, none were found in the genus Streptomyces. The unique genome of these soil- dwelling bacteria, known for their capacity to produce antibiotics, has a high G/C content and diverges substantially from distantly related bacteria. Yet in the non-coding 6S RNA it is the secondary structure that is crucial for its function. The 6S RNAs trap sigma factors by mimicking target promoter sequences in order to help with switching sets of expressed genes during developmental transitions. 6S-like RNA genes in Streptomyces coelicolor have been computationally predicted by comparison of in silico modelled secondary structures of known 6S RNAs. The aim of this thesis was the verification of these 6S-like RNA predictions. The experimental approach was based on RNA co-immunoprecipitation (RNA CoIP), as well as RT- PCR from RNA samples. The outcomes of this project are the detection of six novel ncRNA transcripts with possible 6S-like RNA functions, which also served as the wet-lab verification of the in silico prediction technique...

To understand the pathophysiology of hearing loss, it is necessary to identify genes responsible for embryonic development of neurosensory cells in the inner ear. The aim of this work is to clarify the role of LIM-homeodomain transcription factor ISL1 in the development of these cells. Using Cre-loxP recombination strategy, we generated a mouse line with time and site- specific deletion of Isl1 gene in NEUROD1-Cre expressing cells (Isl1 CKO). Although the early development of stato-acoustic ganglion was not affected by Isl1 deletion, at E14,5, we observed abnormalities in neuronal migration, formation of spiral ganglion and axon guidance in the Isl1 CKO cochlea. The length of the cochlear sensory epithelium was shortened by 20% as a consequence of lower proliferation activity of sensory precursor cells. Our results suggest that ISL1 is necessary for spiral ganglion formation and innervation of the Organ of Corti. Key words: transcription factor ISL1, neurons, Cre-loxP system, mouse model

Meis transcription factors belong to the group of TALE (three amino acids loop extension) homeodomain proteins. Meis2 proteins have a potential role in regulation of neural crest cells development and in differentiation of their derivates. Zebrafish genome has two paralogues of meis2 gene, meis2a and meis2b. CRISPR/Cas9 technology was used to prepare mutant lines of both paralogues, meis2a and meis2b, for the purpose of study of function of Meis2 transcription factors. Specific morpholinos that reduce the expression of meis2a and meis2b were used as controls. Craniofacial and cardiac development in mutant fish was analyzed in the meis2a line by RNA in situ hybridization, histological cartilage staining, and computed tomography. While we observed impaired craniofacial and cardiac development after injection of specific Morpholinos, we did not detect similar changes in the meis2a KO line. Our genetic approach has not clearly shown that the meis2a paralogue itself plays an important role in craniofacial development and cardiac development. For more detailed analysis, further experiments on fish lines with combined meis2a and meis2b knock-outs are needed. Key words Mutagenesis CRISPR, Danio rerio, neural crest cells, Meis2, transcription factor

Analysis of perception of women's fear of crime on the selected area of Malešice Abstract The objective of this thesis is to define all the physical and social fear factors of crime and its share on the subjective perception of women's fear of crime on the selected area of Malešice. As the main research methods the field research was used to identify the factors of fear in space, spatial analysis of the factors of fear and analysis of interviews with the research group of women, aimed to determine the structure of these factors of fear in the individual categories as well as in specific places, where women feel the fear of crime. The theoretical framework of this work is based on the formation and the classification characteristics of the significance of individual fear factors in relation to the perception of the fear of women. Keywords: The fear factor of crime, the perception of women's fear, the place of fear

Adaptation to chronic hypoxia is characterized by a variety of functional changes in order to maintain metabolic and energy homeostasis. It has been known for many years that both humans and animals indigenous or adapted to high-altitude hypoxia are more tolerant to an acute ischemic injury of the heart. HIF1α is found as a primary transcriptional regulator of adaptive response to hypoxia in all tissues, whereas HIF2α is more tissue specific. The activity of HIFα is regualted by prolyl hydoxylases (EGLN). The EGLN1 was shown to be more efficient in HIF1α hydroxylation than in HIF2α. As well as the EGLN3 is more specific for HIF2α . Under hypoxic conditions, HIF activates the transcription of about 70 genes. Hence, HIF1α and HIF2α can play an essential role in pathophysiology of ischemic heart disease. The aim of our study was to determine myocardial expression of HIFs and its regulatory hydroxylases in adult male Wistar rats adapted to continuous normobaric hypoxia (H; FIO2 = 0.1) for 3 weeks. Another two groups of rats were exposed to normobaric hypoxia intermittently for either 8 h/day (INH) or 23 h/day (RH) during the 3-week adaptation period. While H induces protective cardiac phenotype, the later regimen (RH) does not. The protein expression of HIFs, PHDs and FIH were then determined by...

If there was but one important issue to be highlighted concerning Serbian music of the 20th century, it would certainly be the question of musical nationalism. As in all other countries belonging to the so-called European periphery, composers in Serbia faced the problem of asserting both their belonging to the European musical community and specific differences. The former had to be displayed by their musical craftmanship and creative individuality, while the latter were conveyed through the introduction of native folk elements as tokens of a specific identity.

Slovenian identity took shape under cultural, political and economic circumstances that in uenced Western European civilization at its furthest eastern border. Since the 6th century, ancestors of present day Slovenes inhabited the territory of the Eastern Alps, bordering on the Pannonian plains and, in the south, on the Adriatic sea. The decisive elements of Slovenian identity were global historical processes: Christianization, the emergence of historical countries, the Reformation, the Counter-Reformation and the Catholic renewal, the forming of the Austrian monarchy, the enlightenment, romanticism, the rise of nationalism and liberalism, the development of modern democracy. Historical turning points such as Napoleon's Illyrian Provinces, the 1848 'spring of nations', World Wars I and II, and the collapse of Yugoslavia also made an impact on identity formation. These processes affected national consciousness as well as the concept of nation.

In a world of open boundaries where the free circulation of spiritual assets and the impetuous flood of information is assured, it appears natural to attempt to assume the clarification of fundamental concepts regarding the art of sounds such as it has been the case in European countries or, to be more specific, in music composed during the 20th century. This stage that was formerly a privilege of a few centres, later of countries, has now been replaced. The united effort of generations has built an impressive thesaurus, generating patterns taken over by still crystallizing cultures which are, in their turn, creating their own musical patrimony whose powerful propensity needs to be inventoried and made available to other people.