<p>Лукавичко-луковски&nbsp; крас&nbsp; припада&nbsp; Динарском&nbsp; красу.&nbsp; Налази&nbsp; се&nbsp; у&nbsp; средишњем&nbsp; делу Црне&nbsp; Горе,&nbsp; у&nbsp; области&nbsp; површи&nbsp; и&nbsp; брда.&nbsp; Представља&nbsp; западни&nbsp; део&nbsp;&nbsp; Mорачких&nbsp; планина,&nbsp; у висинској зони од 820 до 2050&nbsp; m&nbsp; н.в. Ову област изграђују различите мезозојске карбонатне стене&nbsp; прекривене&nbsp; седиментима&nbsp; квартарне&nbsp; старости.&nbsp; На&nbsp; овом&nbsp; простору&nbsp; формирани&nbsp; су различити&nbsp; генетски&nbsp; типови&nbsp; рељефа&nbsp; са&nbsp; доминацијом&nbsp; крашког&nbsp; рељефа.&nbsp; Просторним&nbsp; и временским&nbsp; преклапањем&nbsp; крашког&nbsp; процеса&nbsp; са&nbsp; глацијалним&nbsp; процесом&nbsp; формиран&nbsp; је&nbsp; сложен глациокрашки&nbsp; рељеф.&nbsp; Плеистоценска&nbsp; глацијација&nbsp; оставила&nbsp; је&nbsp; значајне&nbsp; последице,&nbsp; а&nbsp; као најважнија је засипање краса моренским и претранспортованим моренским материјалом.Применом&nbsp; Schmidt&nbsp; Hammer&nbsp; теста&nbsp; утврђена&nbsp; је&nbsp; релативна&nbsp; хронологија&nbsp; различитих типова&nbsp; квартарних&nbsp; седимената.&nbsp; Реконструкцијом&nbsp; ерозивних&nbsp; и&nbsp; акумулативних&nbsp; облика глацијалног&nbsp; рељефа&nbsp; анализиран&nbsp; је&nbsp; интезитет,&nbsp; обим&nbsp; и&nbsp; број&nbsp; глацијалних&nbsp; фаза.&nbsp; Утврђено&nbsp; је постојање три старије глацијалне фазе и једне млађе, у временском распону од MIS 12 преко MIS&nbsp; 6&nbsp; и&nbsp; MIS&nbsp; 5d&nbsp; &ndash;&nbsp; 2&nbsp; до&nbsp; млађег&nbsp; дријаса.&nbsp; Засипање&nbsp; Лукавичко-луковског&nbsp; краса&nbsp; извршено&nbsp; је моренским&nbsp; материјалом&nbsp; и&nbsp; његовим&nbsp; претранспортовањем&nbsp; од&nbsp; стране&nbsp; флувијланог, денудационог и гравитационог процеса. Засипање је било делимично и потпуно. Делимично засипање извршено је субподинским моренама, док је потпуно засипање везано за просторе<br />чеоних&nbsp; и&nbsp; ивичних&nbsp; морена.&nbsp; Акумулација&nbsp; претранспортованог&nbsp; моренског&nbsp; материјала&nbsp; је највиши степен потпуног засипања краса када су поља, као највећи крашки облици рељефа, у потпуности засута.</p> / <p>Lukavičko-lukovski&nbsp; kras&nbsp; pripada&nbsp; Dinarskom&nbsp; krasu.&nbsp; Nalazi&nbsp; se&nbsp; u&nbsp; središnjem&nbsp; delu Crne&nbsp; Gore,&nbsp; u&nbsp; oblasti&nbsp; površi&nbsp; i&nbsp; brda.&nbsp; Predstavlja&nbsp; zapadni&nbsp; deo&nbsp;&nbsp; Moračkih&nbsp; planina,&nbsp; u visinskoj zoni od 820 do 2050&nbsp; m&nbsp; n.v. Ovu oblast izgrađuju različite mezozojske karbonatne stene&nbsp; prekrivene&nbsp; sedimentima&nbsp; kvartarne&nbsp; starosti.&nbsp; Na&nbsp; ovom&nbsp; prostoru&nbsp; formirani&nbsp; su različiti&nbsp; genetski&nbsp; tipovi&nbsp; reljefa&nbsp; sa&nbsp; dominacijom&nbsp; kraškog&nbsp; reljefa.&nbsp; Prostornim&nbsp; i vremenskim&nbsp; preklapanjem&nbsp; kraškog&nbsp; procesa&nbsp; sa&nbsp; glacijalnim&nbsp; procesom&nbsp; formiran&nbsp; je&nbsp; složen glaciokraški&nbsp; reljef.&nbsp; Pleistocenska&nbsp; glacijacija&nbsp; ostavila&nbsp; je&nbsp; značajne&nbsp; posledice,&nbsp; a&nbsp; kao najvažnija je zasipanje krasa morenskim i pretransportovanim morenskim materijalom.Primenom&nbsp; Schmidt&nbsp; Hammer&nbsp; testa&nbsp; utvrđena&nbsp; je&nbsp; relativna&nbsp; hronologija&nbsp; različitih tipova&nbsp; kvartarnih&nbsp; sedimenata.&nbsp; Rekonstrukcijom&nbsp; erozivnih&nbsp; i&nbsp; akumulativnih&nbsp; oblika glacijalnog&nbsp; reljefa&nbsp; analiziran&nbsp; je&nbsp; intezitet,&nbsp; obim&nbsp; i&nbsp; broj&nbsp; glacijalnih&nbsp; faza.&nbsp; Utvrđeno&nbsp; je postojanje tri starije glacijalne faze i jedne mlađe, u vremenskom rasponu od MIS 12 preko MIS&nbsp; 6&nbsp; i&nbsp; MIS&nbsp; 5d&nbsp; &ndash;&nbsp; 2&nbsp; do&nbsp; mlađeg&nbsp; drijasa.&nbsp; Zasipanje&nbsp; Lukavičko-lukovskog&nbsp; krasa&nbsp; izvršeno&nbsp; je morenskim&nbsp; materijalom&nbsp; i&nbsp; njegovim&nbsp; pretransportovanjem&nbsp; od&nbsp; strane&nbsp; fluvijlanog, denudacionog i gravitacionog procesa. Zasipanje je bilo delimično i potpuno. Delimično zasipanje izvršeno je subpodinskim morenama, dok je potpuno zasipanje vezano za prostore<br />čeonih&nbsp; i&nbsp; ivičnih&nbsp; morena.&nbsp; Akumulacija&nbsp; pretransportovanog&nbsp; morenskog&nbsp; materijala&nbsp; je najviši stepen potpunog zasipanja krasa kada su polja, kao najveći kraški oblici reljefa, u potpunosti zasuta.</p> / <p>The&nbsp; Lukavičko-lukovski&nbsp; karst&nbsp; belongs&nbsp; to the&nbsp; Dinaric&nbsp; karst.&nbsp; It occupies&nbsp; the&nbsp; central&nbsp; part&nbsp; of Montenegro&nbsp; within&nbsp; the&nbsp; area&nbsp; of&nbsp; plains&nbsp; and&nbsp; hills.&nbsp; Representing&nbsp; the&nbsp; western&nbsp; part&nbsp; of&nbsp; the&nbsp; Morača Mountains&nbsp; it&nbsp; is&nbsp; placed&nbsp; between&nbsp; 820&nbsp; to&nbsp; 2050&nbsp; m&nbsp; a.s.l.&nbsp; The&nbsp; area&nbsp; is&nbsp; built&nbsp; by&nbsp; different&nbsp; Mesozoic carbonate rocks and the overlying Quaternary sediments. Among different genetic types of relief, the karst one&nbsp; is prevailing. The spatial and temporal overlap of karst and glacial processes&nbsp; led to complex&nbsp; glaciokarst&nbsp; relief.&nbsp; Pleistocene&nbsp; glaciation&nbsp; left&nbsp; behind&nbsp; considerable&nbsp; changes&nbsp; including&nbsp; the karst filled by moraine and re-transported moraine material as the most significant. Implementing&nbsp; the&nbsp; Schmidt&nbsp; Hammer&nbsp; test&nbsp; the&nbsp; relative&nbsp; chronology&nbsp; of&nbsp; different&nbsp; Quaternary sediments was determined.&nbsp; The intensity, extent, and a number of glacial phases were analyzed by reconstruction&nbsp; of&nbsp; erosive&nbsp; and&nbsp; accumulative&nbsp; forms&nbsp; in&nbsp; glacial&nbsp; relief.&nbsp; The&nbsp; existence&nbsp; of&nbsp; three&nbsp; older glacial phases and a younger once, within&nbsp; the temporal range from MIS 12 over MIS 6 and&nbsp; MIS 5d &ndash;&nbsp; 2 to the Younger Dryas has been resolved. Filling of the Lukavičko -lukovski karst by moraine and&nbsp; re- deposited&nbsp; moraine&nbsp; material&nbsp; under&nbsp; fluvial,&nbsp; denudation,&nbsp; and&nbsp; gravity&nbsp; processes&nbsp; was&nbsp; partial&nbsp; to complete. The former take place by piedmont moraines, while the later were caused by terminal and lateral moraines. Accumulation of re-deposited moraine material&nbsp; is the highest stage of karst filling when karst polje as the largest karst landform becomes completely inhumated.</p>

KRAS ist eines der am häufigsten mutierten Onkogene in Darmkrebspatienten. Dies macht es zu einem guten Ansatzpunkt für gezielte Krebstherapien. Trotz jahrzehntelanger Forschungsbemühungen hat sich jedoch keines der zur Inhibition des mutierten KRAS entwickelten Medikamente klinisch etablieren können. Um eventuelle Schwachstellen von KRAS mutierten Darmkrebszellen aufzudecken, wurde in der vorliegenden Studie ein shRNA basierter Screen in CaCo2 Zellen mit konditioneller KRAS(G12V) Expression ausgeführt. Die maßangefertigte shRNA-Bibliothek umfasste 121 ausgewählte Gene, die zuvor nach MEK Inhibition als stark hoch- oder herunterreguliert identifiziert wurden. Der Screen sowie die Screen-Validierung zeigten, dass KRAS(G12V) exprimierende CaCo2 Zellen besonders sensitiv für den Knockdown des DNA Replikationslizensierungsfaktors Minichromosome Maintenance Complex Component 7 (MCM7) waren, wohingegen sich KRAS(wt) CaCo2 Zellen als weitestgehend resistent gegenüber des MCM7 Knockdowns erwiesen. Ähnliche Ergebnisse wurden im isogenen DLD 1 Zellmodell erzielt. Des Weiteren hat der Knockdown von MCM7 spezifisch in KRAS mutierten Zellen zu erhöhtem Replikationsstress geführt, der durch gesteigerte nukleare RPA Fokalisierung nachgewiesen wurde. Weitere Untersuchungen haben außerdem eine signifikant erhöhte Anzahl an mitotischen Zellen nach gleichzeitigem MCM7 Knockdown und KRAS(G12V) Expression ergeben. Diese Zunahme an mitotischen Zellen wurde zusätzlich von einer stark angestiegenen Anzahl an DNS Schäden in der Mitose begleitet. Das hohe Maß an DNS Schäden in der Mitose kann auf den gesteigerten Replikationsstress zurückgeführt werden, der ungelöst zu einer gestörten Segregation der Chromosomen in der Mitose führt. Zusammenfassend zeigen die Ergebnisse, dass KRAS mutierte Darmkrebszellen sensitiv auf den Knockdown von MCM7 sind. Demzufolge könnte die Inhibition von DNS Replikationslizensierung ein geeigneter Ansatz für die gezielte Therapie von KRAS mutierten Darmkrebs sein. / KRAS ist eines der am häufigsten mutierten Onkogene in Darmkrebspatienten. Dies macht es zu einem guten Ansatzpunkt für gezielte Krebstherapien. Trotz jahrzehntelanger Forschungsbemühungen hat sich jedoch keines der zur Inhibition des mutierten KRAS entwickelten Medikamente klinisch etablieren können. Um eventuelle Schwachstellen von KRAS mutierten Darmkrebszellen aufzudecken, wurde in der vorliegenden Studie ein shRNA basierter Screen in CaCo2 Zellen mit konditioneller KRAS(G12V) Expression ausgeführt. Die maßangefertigte shRNA-Bibliothek umfasste 121 ausgewählte Gene, die zuvor nach MEK Inhibition als stark hoch- oder herunterreguliert identifiziert wurden. Der Screen sowie die Screen-Validierung zeigten, dass KRAS(G12V) exprimierende CaCo2 Zellen besonders sensitiv für den Knockdown des DNA Replikationslizensierungsfaktors Minichromosome Maintenance Complex Component 7 (MCM7) waren, wohingegen sich KRAS(wt) CaCo2 Zellen als weitestgehend resistent gegenüber des MCM7 Knockdowns erwiesen. Ähnliche Ergebnisse wurden im isogenen DLD 1 Zellmodell erzielt. Des Weiteren hat der Knockdown von MCM7 spezifisch in KRAS mutierten Zellen zu erhöhtem Replikationsstress geführt, der durch gesteigerte nukleare RPA Fokalisierung nachgewiesen wurde. Weitere Untersuchungen haben außerdem eine signifikant erhöhte Anzahl an mitotischen Zellen nach gleichzeitigem MCM7 Knockdown und KRAS(G12V) Expression ergeben. Diese Zunahme an mitotischen Zellen wurde zusätzlich von einer stark angestiegenen Anzahl an DNS Schäden in der Mitose begleitet. Das hohe Maß an DNS Schäden in der Mitose kann auf den gesteigerten Replikationsstress zurückgeführt werden, der ungelöst zu einer gestörten Segregation der Chromosomen in der Mitose führt. Zusammenfassend zeigen die Ergebnisse, dass KRAS mutierte Darmkrebszellen sensitiv auf den Knockdown von MCM7 sind. Demzufolge könnte die Inhibition von DNS Replikationslizensierung ein geeigneter Ansatz für die gezielte Therapie von KRAS mutierten Darmkrebs sein. / With KRAS being one of the most frequently altered oncogenes in colorectal cancer (CRC), it is an obvious target for cancer therapy. However, despite enormous efforts over the past three decades to target mutated KRAS, not a single drug has made it to the clinic. To unravel vulnerabilities of KRAS-mutant CRC cells, a shRNA-based screen was performed in CaCo2 cells harboring conditional oncogenic KRAS(G12V). The custom-designed shRNA library comprised 121 selected genes, which were previously identified to be strongly up- or downregulated in response to MEK inhibition. The screen as well as the subsequent validations showed that CaCo2 cells expressing KRAS(G12V) were sensitive to the suppression of the DNA replication licensing factor Minichromosome Maintenance Complex Component 7 (MCM7), whereas KRAS(wt) CaCo2 cells were largely resistant to MCM7 suppression. Similar results were obtained in an isogenic DLD-1 cell culture model. Knockdown of MCM7 in a KRAS-mutant background led to replication stress as indicated by increased nuclear RPA focalization. Further investigation showed a significant increase in mitotic cells after simultaneous MCM7 knockdown and KRAS(G12V) expression. The increased percentage of mitotic cells coincided with strongly increased DNA damage in mitosis. Taken together, the accumulation of DNA damage in mitotic cells is due to replication stress that remained unresolved, which results in mitotic catastrophe and cell death. In summary, the data show a vulnerability of KRAS mutant cells towards suppression of MCM7 and suggest that inhibiting DNA replication licensing might be a viable strategy to target KRAS-mutant cancers.

Title: Project of Educational cycle trail in the Protected Landscape Area in Bohemian Karst Objective: The objective of this work was to create an Educational cycle trail in the Protected Landscape Area of the Bohemian Karst. The trail, natural and cultural attractions and other information process into guidebook which will be available at tourist information centers and on the Internet. Methods: Collecting and sorting information about the natural and cultural wealth of the region. Summarizing information in guidebook and creating a trail. Subsequent test the applicability of a booklet form of a questionnaire to a group of cyclists who created the route with the completed booklets. Results: The results of this work are two proposal of Educational cycle trail in the Protected Landscape Area of the Bohemian Karst, which are processed into guidebook that contains trail description, information about each trail and map material. The final form of the trail is also based on results of questionnaires and direct responses of testees. The guidebook can be offered to information centers in the area of Bohemian Karst or through them be available in electronic form on the Internet. Keywords: cycling, Educational trail, Protected Landscape Area, Bohemian Karst.

The diploma thesis deals with the application of a new instrument for landscape protection and nature conservation which is the foundation of Geoparks, with a particular focus on the candidate Joachim Barrande Geopark. The aim of this paper is not only to assess the impacts of tourism on this area. Management of establishment of the geopark is discussed, too. The thesis emphasizes the current relations, cooperation and attitudes of the actors. Proposals to improve the efficiency of establishment of Geoparks are an integral part of the paper, too. It also critically appreciates the phenomenon of Geoparks, which is widely discussed in the concept of sustainable tourism. The thesis gives an overview of the legislative restrictions related to the protection of nature and implies the confrontation of the nature conservation interests with the interests of tourism. Key words: sustainable development, tourism, geotourism, geopark, Bohemian Karst

La protéine de stress p8 fut découverte et caractérisée dans notre laboratoire. Cette protéine est surexprimée dans l'adénocarcinome pancréatique et possède un rôle dans la progression tumorale. Pendant ce travail de thèse, nous nous sommes focalisé sur le rôle de p8 dans les phases initiales de la tumorigénèse pancréatique et sur ses mécanismes d'action, impliqués dans la progression tumorale. Nous avons montré que p8 joue un rôle essentiel dans l'apparition des lésions PanINs suite à l'activation de l'oncogène Kras. Au niveau cellulaire, nous avons montré que la protéine p8 protège les cellules tumorales pancréatiques contre le stress de la privation en nutriments via la régulation de l'expression de RelB et IER3. La voie p8, RelB et IER3 est impliquée dans l'inhibition de l'apoptose suite au stress. De plus, nous avons observé que ces trois protéines sont co-exprimées dans les adénocarcinomes humains et leur expression corrèle avec l'évolution de la maladie. Dans un second lieu, nous avons démontré le rôle essentiel de la protéine p8 dans la résistance des cellules tumorales pancréatiques à l'hypoxie et à la privation en glucose. Nous avons identifié la voie p8/Aurora KinaseA, qui en réponse au stress métabolique, réduit l'apparition des dommages à l'ADN en contrôlant l'expression des gènes liés au cycle cellulaire et à la réparation de l'ADN. De plus, nos recherches ont montré que p8 protège les cellules tumorales du stress métabolique en inhibant la mort cellulaire dépendante de l'autophagie. Nous espérons que nos résultats aideront à mieux cibler les cellules tumorales pancréatiques et leur caractère résistant au stress micro-environnemental extrême. / The stress protein p8 was discovered and characterized in our laboratory. Over expressed in pancreatic adenocarcinoma, p8 is involved in tumor progression. During my PhD studies, we focused on the role of p8 in pancreatic cancer development and on its mechanisms of action. First, we demonstrated that p8 is essential for PanIN development following Kras oncogene activation. At the cellular level, we found that p8 protects pancreatic cancer cells upon nutrient starvation stress through the regulation of RelB and IER3 expression. p8, RelB and IER3-dependent cascade inhibits apoptosis after the starvation stress. Furthermore, we showed that these tree proteins are co expressed in human pancreatic adenocarcinoma. One the other hand, our study showed that p8 is involved in pancreatic cancer cells resistance to hypoxia and glucose starvation. We identified a p8/Aurora KinaseA pathway which, in response to such metabolic stress, reduces DNA damage by regulating cell cycle and DNA repair genes expression. Moreover, our studies demonstrated that p8/AURKA path protects cancer cells against metabolic stress by inhibiting autophagy-associated cell death. We expect that our data will help to get new therapeutics against pancreatic cancer.

Molluscan succession was studied in 18 abandoned limestone quarries of different age in Bohemian Karst. The number of species in studied quarries increases in the time. The less species were found in the oldest quarries. This trend was probably caused by habitat diversity decline although it is not conclusive. The best predictors of mollusk species composition are type of surrounding vegetation, light and the cover of tree layer. It is important to take into account correlations of the other environmental variables with light and the cover of tree layer. Compositions of mollusk assemblages of north and south-facing slopes differ, but these differences diminish with ongoing succession. Quarries represent suitable model sites for the study of succession.

In the pre-lacation, lactation and post-lactation periods in 2010 and 2011 and the pre-lactation period in 2012 we used radio-telemetry to determine changes in home range and habitat activity and preference of the maternity colony of the Mediterranean horseshoe bat (Rhinolophus euryale) in Slovak Karst. The colony roosted in the attic of the monastery in Jasov. This area represents the northern margin of the species distribution range. In total, we tagged 35 females that were radio-tracked for 31 nights. For the all pre- lactation periods 17 females were marked, in the lactation periods 12 females were marked, and 6 females were marked in the post-lactation periods. The females were marked with radiotags and the VHF telemetry (radio telemetry using very high frequencies) was used. We compared the spatial and habitat preferences in the above defined seasons of the annual reproductive cycle. The total number of recorded locations was 858 for all reported periods. We compared the varios aspects of activity of the females during the night in the particular periods. We have shown that the females left their roost in the pre-lactation periods as the most late. These were followed by the females in the lactation periods and as the most early after the sunsetthe roost was left by the females in the...

This diploma thesis aims at Czech legislation related to conservation of caves both in terms of its link to the protection of caves as subterranean spaces and parts of the natural environment and of its relation to other fields of expertise, including legal studies (e.g., mining law) and other disciplines (e.g., geology, carsology). First, our attention is paid to definition of the term "cave" and to links of the term to natural sciences. Further, we analyse the development of legal conservation of caves and approaches to caves as a subject of legislation per se. The example of Slovenia - being a prominent speleological country with recognized legislation in terms of its quality and detail - is used in order to compare Czech approaches to cave conservation. Concerning the practical issues, we present an example of conservation effort devoted to one single cave in Czechia, which enables to describe functioning of legal conservation tools, including the themes where these tools overlap. We also present and discuss the only one Czech case-law dealing with the legal aspect of caves.

In the region of Bohemian Cretaceous Basin can be found some springs with specific yield over 100 l/s. The doyen of Czech hydrogeology Prof. Hynie described some of those springs to be of karst origin and as the most permeable area he described the so-called transitional facies between shallow-water sandstones and deep-water marlstones. Possibilities of karstification have not yet been studied for rocks in the BCB, so the origin of well-permeable pathways in the BCB is a subject of speculations. This thesis deals with the question of which sedimentary rocks potentially allow the generation of karst permeability in the BCB. To do so, rock samples drilled from outcrops in the BCB were subjected to a fast dissolution simulation by leaching in hydrochloric acid. Carbonate content is measured by a standard and one's own method. Mineral composition, grain size and microscopic structure of rocks are studied with SEM. As is shown, the border of rock karstification is not defined just by the carbonate content, but also the grain size, rock structure and by the occurrence of fine secondary silicate content. Concerning the amount of dissolvable compounds, the border of total disintegration can be at 30 % of carbonate content for some rocks, but the most resistant rocks (mostly fine rocks with SiO2 matrix) stay intact...

Charakteristika území Moravského krasu. Zpřístupněné jeskyně, propast Macocha. Historické, kulturní, církevní a technické památky. Materiláně technická základna Moravského krasu. Ochrana životního prostředí a speleoterapie. Průzkum povědomosti občanů ČR o CHKO Moravský kras. Swot analýza Moravského krasu