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The role of ATM in breast cancer
Soukupová, Jana ; Pohlreich, Petr (advisor) ; Souček, Pavel (referee) ; Foretová, Lenka (referee)
Incidence of breast cancer is continuously increasing in the Czech Republic. Tumor development is a result of gene alterations'accumulation, particulary associated with genes involved in regulation of cell growth and division. Hereditary carcinomas account for approximately 5-10% of all breast tumors and in 60-80% cases are caused by a germline mutation in the major predisposition genes BRCA1 and BRCA2. Nevertheless, other genes, mostly of lower penetrance, may play a role in breast pathogenesis such as the ATM tumor-suppressor gene. ATM is the apex of the repair pathway of DSB. This protein kinase activates through phosphorylation of its substrates cell cycle checkpoints, which leads either to the delay of the cell cycle progression until DSB are repaired or to the promotion of apoptosis. To sum up, the ATM gene seems to have a role in breast cancer development in a minority of the high-risk families in our population which is significantly lower compared to BRCA1/2 and it also seems to be involved in pathogenesis of sporadic breast cancer. Despite the ATM gene's length, we do not perform the preventive screening of this gene in breast cancer high-risk families. Nevertheless, we offer the molecular diagnostics of ATM to ataxia telangiectasia patients.
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Molecular factors of artherogenesis in chronic kidney disease with experimental model of chronic inhibition of Nitric Oxide Synthesis and its Effect of HMG-CoA reductase inhibitoin
Lecian, Dalibor ; Matouš, Bohuslav (advisor) ; Tesař, Vladimír (referee) ; Zadražil, Josef (referee)
The experimental part of the thesis covered the markers involved in nitric oxide deficiency model in rats. The analogue of arginine N-nitro- L -arginine-methyl ester ( L -NAME) was used. L -NAME administration resulted in sustained elevation of BP, decreased GFR, and in higher albuminuria compared to control animals. The administration of hypolipidemic drug - atorvastatin to Wistar rats was studied. The statin used caused lower albuminuria and prevented decreases in GFR in L -NAME rats without having an impact on hypertension. CAV1 protein expression was similar in all groups of rats. In contrast, VEGF expression and RhoA activity was increased in L -NAME-treated animals, and normalized with coadministration of atorvastatin. Clinical part of the thesis focused on the analysis of markers of oxidative stress in obese and non-obese patients with CKD and after kidney transplantation. The patients with CKD had elevated serum concentrations of AGEs, sRAGE and ADMA with the maximal concentrations of AGEs in the patients on hemodialysis. The successful kidney transplantation decreases the AGEs, sRAGE and ADMA concentrations but not to normal value according to general population. Patients with obesity exhibited lower concentrations of sRAGE in CKD as a protective factor for cardiovascular disease. Concentrations of...
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Business methods regarding export of capital goods
Dobyšarová, Adéla ; Černohlávková, Eva (advisor) ; Nejedlý, Michal (referee)
This bachelor thesis is devoted to the analysis of business methods regarding export of capital goods, particularly of tenders and PPP projects. Due to the longevity, complex relationships and financial demands regarding exports of capital goods, the thesis also focuses on methods of financing export of capital goods. Legislation regulating public procurement and PPP projects at the global, European and national level is also mentioned. Recently, Czech exporters get increasingly involved in the international supply of capital goods, many domestic enterprises in the role of general contractor. I will introduce several successful exporters of capital goods and also focus on export opportunities for Czech companies.
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The analysis of Executive Search company in the context of Czech labor market
Horák, Jan ; Šikýř, Martin (advisor) ; Němec, Otakar (referee)
The theoretical part of this thesis describes internal and external ways that can be of use while appointing employees. The thesis is focused on using direct systematic search (Executive Search) in the environment of consulting company CSP Partners Ltd. and its aim is to show the specific features of this method usually used to appoint specialists or managers. Commercial and executive processes of the company are depicted within the text. Using analytical tools this thesis examines the whole HR consulting industry in the context of Czech labor market. Historical development and recent trends are included, ethical dimension as well as motivation of candidates approached using this method are described as well. Many practical notes are involved and the final part describes one of CSP Partners' Ltd. projects in detail.
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Working environment
Fialová, Michaela ; Reichel, Jiří (referee) ; Kocianová, Renata (advisor)
A person's working environment is one of the places that he/she spends a large part of his/her time, and that is the reason why it is necessary to dedicate sufficient attention and care to it. This care involves optimizing working conditions- which influence the activity and productivity of employees- and creating a pleasant atmosphere in workplace. If this care for working environment is taken as a whole, it reaches beyond social-psychological conditions to the actual conditions of the working station, which are called the physical factors. These factors are present in every type of workplace (whether in digger or smaller quantity) and they can markedly influence the mood of employees, the overall atmosphere of the workplace and finally also the achievement of individual employees. The physical conditions of work are composed of: noise, lighting, choice of colors, the conditions of microclimate, design of workplace, and last but not least ergonomically suitable tools and working equipment the worker uses. Almost all mentioned items have recommended limits and specification and quiet frequently they are regulated by sanitary codes and legislature.
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Banks and their market entry strategy
Sessa, Gionni ; Král, Petr (advisor) ; Machek, Martin (referee)
In the global market in which many countries still struggle with the consequences of the financial crisis of 2008, many companies come to the conclusion that growth can be achieved through international marketing activities. This attitude poses big challenges to organization that want to enter the international arena, involving deciding which markets should be entered, how this should be done, through which marketing program and finally how to organize the marketing. International expansion poses risks as well as opportunities to businesses, and it is crucial for the organization to thoroughly evaluate the market in order to take a decision about the market entry strategy. Based on the case studies of Credit Suisse and UBS entering the Brazilian market, this thesis sought to study how Swiss banks entered the country and with what results. Based on an extensive literature review, the two cases have been presented and it was possible to demonstrate that great cultural difference and tight regulation suggest the entry through a merger or an acquisition.
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Distribution of CD46 and β1 integrin molecules with respect to different membrane structures of the sperm head
Šebková, Nataša ; Frolíková, Michaela ; Děd, Lukáš ; Dvořáková-Hortová, Kateřina
CD46 protein plays an important role during fertilization and its role is associated with acrosome stability. CD46 is probably involved in signalling pathways triggering the acrosome reaction (AR). It also associates through membrane integrins with specific MAP kinases involved in the AR. Our aim was to monitor the dynamics of relocation of CD46 and β1 integrin during sperm maturation and its preparation for the fertilization. The dependence of this localization changes on the dynamic of actin cytoskeleton was studied. Our results show the changes in the localization of these proteins associated with the AR and their co-localization was observed using proximity ligation assay. After the AR CD46 and β1 integrin spreads across the sperm head, entering the post-acrosomal compartment, and permeates the borders of different domains. It was shown previously that actin dynamics is necessary for acrosome reaction-associated translocation of Izumo1 protein that is required for sperm-egg fusion. Therefore Latrunculin A was used during sperm incubation. The co-incubation of capacitated sperm with Latrunculin A leads to a decrease of the percentages of sperm, which express relocation pattern after induced AR. 3D models and visualizations of potential membrane processes responsible for the relocation of proteins from the acrosomal area to the other compartments of the sperm head were prepared. Our results deliver new information that proteins CD46 and β1 integrin undergo dynamic relocation towards the sites of sperm-egg fusion during the AR in vitro. The inhibitor of actin dynamics abrogates significantly the AR-associated changes in proteins localization. We speculate that this relocation is of importance for the successful sperm-egg interaction, adhesion and subsequent gamete fusion.
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Expression of selected proteins in sperm in men with normal and pathological spermiograms using monoclonal antibodies
Pěknicová, Jana ; Čapková, Jana ; Dorosh, Andriy ; Margaryan, Hasmik ; Kubátová, Alena ; Děd, Lukáš
Recent studies show that infertility in human populations it affects an estimated 15% of couples of reproductive age. Male infertility is the primary cause for 60% of these cases. For these reasons, we analyzed the acrosomal and sperm surface proteins in men with normal and pathological spermiograms. We found that intra-acrosome proteins: TERA (Transitional endoplasmic reticulum ATPase), GAPDHS (Sperm Glyceraldehyde-3-phosphate dehydrogenase), and PRKAR2A (C-AMP-dependent protein kinase II, PRKAR2A), which can be identified using our monoclonal antibodies, are different express in healthy men and men with astenozoospermia (with reduced sperm motility), and with a significantly reduced expression in the astenozoospermia. These proteins are involved in energy metabolism and apoptosis of the cells, and some of them in the sperm-egg interaction; therefore, they have an important role in reproduction. On the other hand, there were no statistically significant differences in the expression of surface proteins (Appolipoprotein J (Clusterin) and Semenogelin). Our findings show that astenozoospermia as a complex disorder of the semen is often combined with other pathological conditions that are not diagnosed by the semen analysis. Therefore monoclonal antibodies are so suitable instrument for the detection of proteins associated with the pathology of the sperm in the semen with low sperm motility. In general, monoclonal antibodies against the sperm proteins are an appropriate tool to detect sperm quality in reproductive medicine.
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Estrogen receptor beta (ERβ) in testicular cells and sperm
Dostálová, Pavla ; Žatecká, Eva ; Děd, Lukáš ; Dorosh, Andriy ; Postlerová, Pavla ; Jonáková, Věra ; Dvořáková-Hortová, Kateřina ; Pěknicová, Jana
Estrogen is a steroid hormone that plays an important role during sperm development in the male and female reproductive tract. Estrogen signalling is a complex process that depends on cell milieu and presence of receptors. Thanks to the steroid nature of estrogens, they can pass through the plasmatic membrane and bind to the intracellular estrogen receptors (ERs). Within the cell, there are several pools of ERs. One of them is localized to the cell nucleus and their activation leads to direct or indirect binding to DNA and ultimately to alternation in gene expression (genomic pathway). Other pools of ERs are associated with plasma membrane or are located in cytosol. Activation of membrane associated ERs leads to rapid non-genomic responses. Nowadays, two classical estrogen receptors are known – ERα and ERβ. Since ERβ is a predominant variant in testes, we focused our study on expression of ERβ variants in murine testes and sperm. We detected two variants of ERβ at mRNA level in both, testes and sperm. These variants differ in 54 nucleotids within the ligand binding domain and this variability results in different affinity to estrogen. We analyzed individual testicular cell types (spermatogonia, spermatocytes, spermatids, Sertoli cells) by RT-qPCR. Our results suggest that both ERβ variants are coexpressed in the same cell type and may therefore interact together. This may have consequences in mediating of estrogen signalling. Moreover, ERβ is expressed more in the later stages of spermatogenesis suggesting the role of ERβ in these stages or alternatively in spermatozoa alone. At the protein level, we detected ERβ in nuclear, membrane and cytosolic fraction prepared from testicular tissue suggesting the involvement of both, genomic and non-genomic, pathways of estrogen signaling in testes. In sperm, anti-ERβ antibodies localized ERβ in acrosome region and tail which is in accordance with the known role of estrogen on capacitation, acrosome reaction and motility.
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