This diploma thesis deals with transformation of the cultural landscape in the cadastral areas of Jihlava and Náměšť nad Oslavou. The theoretical part, referring to the cultural landscape of the Czech Republic, is described in depth and in the form of a literature research. Subsequently, the characteristics of the sites are explored, focusing on physical-geographical, historical, demographic, ethnographic and cultural issues, including identification of the specifics and their comparison. In the practical part, transformation of the landscape of both locations is recorded within the last 60 years, using a questionnaire survey, SWOT analysis and aerial photography. The results have proved the transformation of the cultural landscape to be evident, especially an extensive decrease of agricultural land in Jihlava and an increase of other areas in Náměšť nad Oslavou. Both defined hypotheses were confirmed.

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The diploma thesis deals with teaching the local region on the second stage of primary school. The main aim is oriented on creation design concepts of the curriculum to teach the local region of Žďár nad Sázavou. The diploma thesis consists of three parts. The theoretical part deals with the geographical characteristics of the monitored area, the role of the curriculum in the context of current curricular documents in the Czech Republic and modern methods of teaching geography at the 2nd stage of primary school. In the research part there are developed and evaluated the results of the survey conducted in selected primary schools. The practical part includes educational materials in the form of two multimedia textbooks, worksheets for pupils and methodological guides for teachers.

This dissertation deals with the impact of the agricultural enterprise ZEMPO VOS a.s on the employment and the quality of life in the town Strunkovice nad Blanicí in the period from 1950 to 2013. The main aim was to map out the employment in the town of Strunkovice nad Blanicí including the description of the head employer, the agricultural enterprise in last 60 years in detail. The combination of qualitative and quantitative methods was used to reach the aim. Particularly the study of historical documents, operating data of the agricultural enterprise, interviews with the mayor and with chairman of the board of directors of the holding and questionnaire for inhabitants and for employees. Next was evaluated the financial situation of the holding using selected economic indicators and based on SWOT analysis were identified the strengths and the weaknesses, opportunities and threats. The conclusion outlines the set of certain socio-technical recommendations for stabilization, competitiveness and development of the ZEMPO-VOS a.s. Strunkovice nad Blanicí in the way, that in the future this holding will bring the career opportunities for people living in Strunkovice nad Blanicí.

Nowadays brownfields objects matter not only in major industrial cities, but also in small settlements and rural areas. Even there are abandonned and dilapidated agricultural areas, farms and other buildings as a result of declining employment rate in the primary sector, growing interest in the service sector or increasing import of agricultural production. Abandonned buildings induce a negative aesthetic appearance of the landscape and disrupt the quality of life of residents nearby.

Les maladies neurodégénératives se caractérisent par une déconnexion synaptique et une dégénérescence des axones (DA) précoces, menant à la mort spécifique d’une population neuronale. Les niveaux intracellulaires de NAD+, co-facteur essentiel dans le maintien de l’intégrité axonale, sont fortement diminués lors de ces pathologies. L’augmentation des taux de NAD+ est ainsi une stratégie thérapeutique dans la prévention de ces maladies. La capacité du nicotinamide riboside (NR) à retarder la DA dans le système nerveux périphérique (SNP) ainsi que la récente mise en évidence d'une conversion extracellulaire du NAD+ en NR dans des lignées cellulaires et dans le SNP soulignent l'intérêt de ce précurseur du NAD+. Mon projet de thèse repose sur la caractérisation des effets du NAD+ et du NR lors de la DA dans des neurones du système nerveux central (SNC). A partir d'un modèle d'excitotoxicité mis au point en dispositifs microfluidiques, nous montrons pour la première fois que le NR protège de la DA dans des neurones corticaux de manière plus efficace que le NAD+. Cet effet différentiel a également été validé dans un modèle ischémique in vivo. De manière surprenante, lors d'une neurodégénérescence induite par une déplétion aigüe en NAD+, un effet protecteur total à la fois du NAD+ et du NR a été mis en évidence. L'analyse de la voie de conversion extracellulaire a ainsi révélée une adaptation du métabolisme du NAD+ et de sa conversion en NR en fonction du paradigme neurotoxique. En conclusion, ce travail démontre un fort effet protecteur du NR dans le SNC et ouvre de nouvelles voies thérapeutiques dans la prévention des processus neurodégénératifs. / Synaptic and axonal degeneration (AxD) are major events in neurodegenerative diseases. Levels of NAD+, an important coenzyme for axonal integrity, are strongly reduced in different degeneration models so enhancing cellular NAD+ is one of the numerous therapeutic strategies against neuronal pathologies. Nicotinamide riboside (NR) is a good NAD+ precursor as it has already been shown to delay AxD in peripheral nervous system (PNS) and extracellular NAD+ conversion to NR was previously described in cell lines and in PNS. During my thesis project, we analyzed the role of NR metabolism to prevent degeneration processes in cortical neurons. Using an excitotoxicity model developed in microfluidic devices, we showed for the first time that both NAD+ and NR delay AxD in cortical neurons, with a more potent effect for NR. We confirm this differential effect in an in vivo ischemic model. Moreover, NR effect is mainly restricted to the axonal compartment and intracellular NAD+ depletion is reverted after NR application, suggesting that axonal integrity is totally dependent on NAD+ local metabolism. Furthermore, in a complete NAD+ depletion paradigm, NAD+ and NR have surprisingly the same strong effect, protecting equally neuronal death and AxD. Examination of the extracellular pathway suggest that NAD+ conversion to NR is limited in excitotoxicity but effective in the NAD+ depletion model. These results reveal that NR and NAD+ metabolism depend on the neurotoxic paradigm. Our results demonstrate that NR has a strong and local neuroprotective effect on AxD in several neurotoxic processes. These findings open new therapeutic strategies to prevent neurodegenerative diseases.

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Evidências têm mostrado que as espécies reativas de oxigênio (ROS) geradas pela NAD(P)H oxidase são importantes moduladores de diversas funções celulares como migração, crescimento, proliferação e sobrevivência. Estudos recentes demonstraram o envolvimento da atividade da NAD(P)H oxidase no crescimento e sobrevivência de células de melanoma. Neste trabalho, investigamos o efeito da inibição da NAD(P)H oxidase por difenileneiodônio (DPI) sobre o crescimento das células de melanoma humano MV3 e observamos que este composto reduziu o crescimento destas células em aproximadamente 50%. A inibição da NAD(P)H oxidase induziu mudanças no formato celular, com arredondamento, diminuição do espraiamento e descolamento celular. Esta redução foi acompanhada por um rearranjo do citoesqueleto de actina, diminuição da fosforilação no resíduo Tyr397 da quinase de adesão focal (FAK) e redução na associação de FAK com actina e com a tirosina quinase c-Src. Isto indica que a inibição da geração de ROS está modulando negativamente vias de sinalização ativadas por integrinas, o que freqüentemente conduz a um tipo particular de morte celular conhecida por anoikis. Comprovando a ocorrência deste fenômeno, observamos que a inibição da atividade da NAD(P)H oxidase aumentou a apoptose das células de melanoma e induziu a ativação da caspase-3. Nossos resultados mostram ainda que a inibição da viabilidade celular por DPI foi revertida com o pré-tratamento das células MV3 com um inibidor de tirosina fosfatases (ortovanadato de sódio). Em resumo, este estudo mostra que a geração de ROS por NAD(P)H oxidase está envolvida nos mecanismos de sobrevivência em células de melanoma, uma vez que afetam as vias de sinalização dependentes de FAK-Src, através da inibição da atividade de proteína tirosina fosfatases. / NAD(P)H oxidase-derived reactive oxygen species (ROS) have emerged as critical mediators of several cell functions as diverse as migration, growth, proliferation and survival. Recent evidence has show that NAD(P)H oxidase activity is essential to melanoma proliferation and survival. We reported that NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI) inhibited melanoma growth. NAD(P)H oxidase inhibition induced changes in cell shape with cell spreading decrease, rounding up and detachment. These phenomena were accompanied by rearrangement of actin network and a decrease in both focal adhesion (FAK) phosphorylation in Tyr397 residue and in FAK association to actin and c-Src, indicating that inhibition of ROS generation would down- modulate integrin-mediated signaling, what often results in a particular type of apoptotic cell death, known as anoikis. We observed that NAD(P)H oxidase inhibitor induced apoptosis in melanoma cells with activation of caspase-3. We results show that the effects promoted by NAD(P)H oxidase inhibition on melanoma growth were completely abolished by the pre-treatment of MV3 cells with the protein tyrosine phosphatases inhibitor sodium orthovanadate. In conclusion, our results strongly suggest that ROS generated by NAD(P)H oxidase complex transmit cell survival signals in melanoma cells through the FAK-Src pathway, probably inhibiting protein tyrosine phosphatases.

The aim of this dissertation was firstly to review and analyze an effectiveness of a current precaution oriented on pheasant protection strategy including its economic costingness, all within the selected hunting district in Přerov nad Labem. Secondly to try to find and suggest an own solution in order to improve the protection and conditions applicable to occurrence and reproduction of pheasant.

In January 2015, a zero gambling tolerance came into force in Jablonec nad Nisou, which prohibited casinos and playrooms. It is generally assumed that gambling increases criminality, but the effect in the Czech Republic has not been quantified yet. Based on the regression analysis of monthly data from 2013-2016 this work examines the hypothesis of the existence of a negative relationship between gambling regulation and crime by using the difference in differences method. The town of Semily was used as a control group. This hypothesis is confirmed based on the used model - the regulation of gambling in Jablonec nad Nisou is associated with the average monthly decrease of the total crime rate by 0.3622 crimes per 1000 inhabitants (16% decrease) and the average monthly decrease of the property crime rate by 0,3871 crimes per 1000 inhabitants (30% decrease).

La cardiomyopathie dilatée (CMD) est caractérisée par une fraction d’éjection (FE) réduite, une fonction systolique altérée, une désorganisation de la matrice extracellulaire et des défauts métaboliques. Dans différents modèles de CMD, le niveau d’expression de la nicotinamide riboside kinase 2 (Nmrk2) impliquée dans la synthèse du NAD, un coenzyme majeur du métabolisme énergétique et une molécule de signalisation, est augmenté. NMRK2 est identique à « Muscle Integrin Binding Protein » se liant à l’hétérodimère intégrine β1/α7. Le rôle de Nmrk2 dans le cœur n’est pas connu. Les souris Nmrk2-KO jeunes développent une réponse hypertrophique concentrique normale en réponse à l’angiotensine II et à la constriction aortique. Les échocardiographies jusque 8 semaines post-TAC et au cours du vieillissement à l’état basal, montrent une diminution plus sévère de la FE et un développement de CMD. Les RT-QPCR montrent une augmentation du niveau d’expression de l’isoforme lente β de myosine. NMRK2 n’est pas requise pour maintenir le taux de NAD dans le cœur en réponse aux traitements pro-hypertrophiques et à un âge jeune. Par contre, au cours du vieillissement, les niveaux d’expression de Nmrk1 et Nampt sont diminués et à 24 mois, le NAD myocardique est réduit de 50% chez les souris Nmrk2-KO. A ce même âge, le complexe α7β1 est réduit. Les analyses histologiques montrent un défaut du dépôt de la laminine, la présence d’une fibrose et un élargissement de l’espace intercellulaire chez le mutant Nmrk2-KO. NMRK2 est requise pour préserver la fonction et la structure cardiaque et l’homéostasie du NAD à un âge avancé. Des composants moléculaires modulant sa voie pourraient être une option thérapeutique. / Dilated cardiomyopathy (DCM) is a severe heart disease characterized by reduced ejection fraction, altered systolic function, extracellular matrix disorganization and metabolic defects. In different mice models of DCM, the expression of the nicotinamide riboside kinase 2 (Nmrk2) implicated in the synthesis of NAD, a major coenzyme in energy metabolism and a signaling molecule, is increased. NMRK2 is similar to the muscle integrin binding protein (MIBP) that binds to the integrin α7β1 heterodimer. The role of Nmrk2 in the heart is unknown. Young Nmrk2-KO mice develop a normal cardiac hypertrophic response to angiotensin-II exposure and transverse aorta constriction (TAC) but follow-up echocardiography until 8 weeks post-TAC and during aging from 5 to 24 months revealed a more severe decrease in the EF and the development of a DCM phenotype. RT-qPCR analysis of cardiac mRNAs showed an increase in the slow, cardiac, β myosin heavy chain isoform starting at 12 months. NMRK2 was not essential to maintain myocardial NAD levels in response to pro-hypertrophic treatments and in young adults. However Nmrk1 and Nampt expression level declined strongly with aging and Nmrk2-KO mice displayed a 50% reduction in myocardial NAD levels at 24 months. The α7β1 integrin complex was repressed at this age. Immunofluorescent analyses and electron microscopy revealed a defect in laminin deposition and enlarged intercellular space in the Nmrk2-KO heart. The Nmrk2 gene is required to preserve cardiac function and structure during aging and becomes indispensable for maintaining NAD at late age. Molecular characterization of compounds modulating this pathway could give future therapeutic prospect.