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The development and maintenance of neurons in the inner ear
Wirthová, Natália ; Pavlínková, Gabriela (advisor) ; Pysanenko, Kateryna (referee)
Hearing loss is among the most frequent disabilities. Neurosensory hearing loss is permanent and results from the death of neurons or sensory cells, which have little ability to regenerate in the inner ear (cochlea). Identifying the genes that are associated with generating differentiated and functional sensory cells, neurons, and with hearing loss could provide tools for neurosensory regeneration therapy and preventive measures. Recent data suggest that the prevention of neuronal loss and enhancement of long- term maintenance of neurons are the most important targets for the immediate future. This work is focused on transcription factors and signaling pathway networks that regulate the development and maintenance of neurons in the inner ear.
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Signaling Pathway for Butanol Production in Solventogenic Clostridium Bacteria
Musilová, Jana ; Škutková, Helena (referee) ; Sedlář, Karel (advisor)
Diplomová práce se zabývá studiem signální dráhy produkce butanolu bakterií rodu Clostridium. V první části pojednává o modelování signálních drah pomocí metod systémové biologie. Navazuje popisem zisku dat pro tvorbu a úpravu modelů signálních drah s hlavním zaměřením na techniky pro zjištění genové exprese, produkce a fenotypu. Třetí sekcí je získání základního modelu signální dráhy zapojené do produkce butanolu u solventogenních klostridií. Posledním bodem a zároveň hlavním cílem je vytvoření dynamického modelu signální dráhy produkce butanolu kmene Clostridium beijerinckii NRRL B-598, jeho vyhodnocení pomocí statické a dynamické analýzy a srovnání s biologickými daty.
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Basement membrane and the role of matrix metalloproteinases during embryonic wound healing
Kadlčíková, Dominika ; Šindelka, Radek (advisor) ; Tolde, Ondřej (referee)
The healing process is an attractive topic in biology and medicine. There are two types of wound healing - in embryos and in adults. In the case of embryonic wound healing the whole process is simplified and accelerated. An inflammatory reaction typical for adult healing is eliminated and the wound is healed without scars. Better understanding of embryonic wound healing could lead to more effective treatment of injuries, burns and chronic wounds in human population. The studying of molecular mechanisms in the healing process is also meaningful in the context of understanding the cancer regulation. The wound healing could be compared with embryonic development in many ways. The body's axes are essential for a spatial activation of genes involved in development. Our hypotesis was that the axis are also important for wound healing. It has been suggested that the cell's polarity and motility depends whether the wound is vertical or horizontal. There are also connections between wound healing and cancer development. One of them is the degradation of the basement membrane (BM) and extracellular matrix (ECM). The process of degradation is catalyzed by the coordinated action of several classes of enzymes. Some of them - matrix metalloproteinases (MMP) and their role in embryonic wound healing have been...
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Measurement of signalling pathway activation in mouse macrophage line IC-21 and primery dendritic cells after infection with tick-borne encephalitis virus.
Kožantová, Jana ; Lieskovská, Jaroslava (advisor) ; Drbal, Karel (referee)
Tick-borne encephalitis is a serious disease of the central nervous system. It is caused by tick-borne encephalitis virus, which is transmitted by ticks. The Czech Republic is one of the countries with the highest prevalence of this disease. Tick-borne encephalitis virus is able to replicate in several cell types. In this work we focused on macrophage line IC-21 and dendritic cells, because these cells are the first, which encounter the virus and support its spreading in the host at early stage of infection. So far there is not known any specific receptor for virus entry into cells or which signaling pathways activates. Therefore, we decided to investigate the activation of selected signaling pathways after infection with tick-borne encephalitis virus and influence of tick saliva on this activation. We employed methods of dual luciferase reporter assay, immunosandwich assay and western blot. The obtained results showed that in virus infected IC-21 cells are activated phosphatidyl-inositol pathway, NF-κB pathway, signaling molecule Erk1/2 and others. Testing of tick saliva effect revealed significantly decreased activity of NF-κB, AP-1 and CREB.
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Important mechanisms of tumorigenesis and their role in chemoresistance of head and neck cancers
Zlámalová, Viktorie ; Šírová, Milada (advisor) ; Zíková, Martina (referee)
Head and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide. Despite improvements in therapeutic outcomes due to advances in surgery, radiotherapy, chemotherapy, and imaging techniques, HNSCC still has high mortality rate. For patients who are not cured with surgery and radiotherapy, there are few effective treatment options. Although HNSCC is heterogeneous in nature, current molecular classification distinguishes only human papilloma virus positive and negative tumors. HNSCC in general are characterized by considerable resistance and high rate of locoregional recurrence. Loss of p53 control pathway and numerous alterations in components of intracellular signaling pathways are consistently observed throughout the majority of HNSCC cases, supporting uncontrolled proliferation. It was proven that common mutations in the HNSCC genome play major role in tumorigenesis as well as in resistance to chemotherapy. The aim of the thesis is to describe the important mechanisms in HNSCC, which are associated with mutations in epidermal growth factor receptor and p53, and those including PI3K/Akt/mTOR and Notch signaling pathways. Association of these pathways with chemoresistance to commonly used drugs and even to advanced targeted therapeutic agents was evidenced by many...
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Signaling pathways and genes regulating oocyte maturation in pig
Blaha, Milan ; Procházka, Radek (advisor) ; Krylov, Vladimír (referee) ; Petr, Jaroslav (referee)
The gonadotropin-induced resumption of meiosis and cumulus expansion in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like factors, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. In vitro, the EGF-like peptides are also produced in cumulus cells upon stimulation by FSH. Both FSH and the EGF-like peptides stimulate resumption of meiosis and cumulus expansion in vitro via activation of a broad signaling network in cumulus cells. To define signaling pathways that drive FSH- and AREG-induced cumulus expansion and meiotic resumption, in vitro cultured pig cumulus-oocyte complexes (COCs) were treated with specific protein kinase inhibitors. The results document that FSH-stimulated, but not the AREG-stimulated resumption of meiosis, depends on the PKA and MAPK14 activities; both modes of stimulation require activation of EGFR and MAPK3/1. To characterize the effects of FSH and EGF-like peptides on gene expression in cumulus cells, transcriptomes of cumulus cells were analysed using microarray approach. Both FSH and AREG+EREG increased the expression of genes associated with regulation of cell proliferation, blood coagulation and extracellular matrix remodeling. In contrast to AREG+EREG, FSH also increased the expression of genes coding...
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Signaling pathways and genes regulating oocyte maturation in pig
Blaha, Milan
The gonadotropin-induced resumption of meiosis and cumulus expansion in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like factors, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. In vitro, the EGF-like peptides are also produced in cumulus cells upon stimulation by FSH. Both FSH and the EGF-like peptides stimulate resumption of meiosis and cumulus expansion in vitro via activation of a broad signaling network in cumulus cells. To define signaling pathways that drive FSH- and AREG-induced cumulus expansion and meiotic resumption, in vitro cultured pig cumulus-oocyte complexes (COCs) were treated with specific protein kinase inhibitors. The results document that FSH-stimulated, but not the AREG-stimulated resumption of meiosis, depends on the PKA and MAPK14 activities; both modes of stimulation require activation of EGFR and MAPK3/1. To characterize the effects of FSH and EGF-like peptides on gene expression in cumulus cells, transcriptomes of cumulus cells were analysed using microarray approach. Both FSH and AREG+EREG increased the expression of genes associated with regulation of cell proliferation, blood coagulation and extracellular matrix remodeling. In contrast to AREG+EREG, FSH also increased the expression of genes coding...
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Molecular mechanism of anti-cancer activity of selected natural compounds.
Smolová, Dagmar ; Vališ, Karel (advisor) ; Flieger, Miroslav (referee)
Molecular mechanism of anti-cancer activity of selected natural compounds Přírodovědecká fakulta Univerzity Karlovi v Praze Smolová Dagmar Nowadays, cancer is affecting more then a third of the world's population and it's the cau- se of more than 20% of all deaths. A better understanding of cancer at the epigenic, gene- tic, molecular and cellular levels is opening up lots of opportunities to intervene with the goal of preventing end-stage of the invasive disease. Recently, much attention is paid to the natural substances because of its ability to interact specifically in the tumorgenesis. This compounds are preferred before the standard treatment because of its availability and safe- ty. In this work, there were observed the effects of 6-shogaol, 6-gingerol and galangin in the leukemic cells Jurkat. The greatest efficiency was showed by 6-shogaol wich caused apoptosis in cells by activating the antiproliferative signalling of Hippo pathway and it also decreased the expression of C-MYC oncogene. There was also a decline of C-MYC onco- protein wich has a key role in the tumor cells metabolism through it's ability to provide enought of energy for the growth and active proliferation. (In Czech)
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Interaction studies of insulin, IGF-1/2 and IGF-1 analogue with insulin and IGF-1 receptors
Chrudinová, Martina ; Ryšlavá, Helena (advisor) ; Liberda, Jiří (referee)
Insulin-like growth factors 1 and 2 (IGF-1/2) are single-chain peptides exerting homology (in both amino-acid sequence and tertiary structure) to insulin. The main function of these peptides is promoting celular growth, proliferation and differentiation. Both insulin and insulin-like growth factors mediate their function through membrane receptors - insulin receptor (isoforms A and B) and IGF-1 receptor. All these receptors are members of the tyrosinkinase family of receptors and they exert the same subunit and domain composition. The activation of insulin and IGF-1 receptors is tightly associated with activation of two intracellular signaling pathways. The PI3-K/Akt pathway is involved in the glucose transport to the cell, induction of proliferation or inhibition of apoptosis, while the Ras/MAPK pathway is involved mainly in the induction of cell growth and differentiation. Due to the structure similarity in both the ligands and receptors, every ligand can activate different receptors (with different potency) and the signaling pathways associated with these receptors. Thus, the functions of IGFs and insulin, the same as their receptors, are overlapping. The distinct function of the concrete ligand can be distinguished by the different tissue distribution of both isoforms of insulin receptor and...
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Molecular mechanisms of apoptosis induction in cancer cells.
Fenclová, Tereza ; Novák, Petr (advisor) ; Milichovský, Jan (referee)
Cancer diseases are now the third leading cause of death (20% of all deaths). It is therefore important to find new ways of getting tumor cells effectively and specifically disposed of and a promising path is targeted therapy. One of the most frequently deregulated protooncogenes in cancer is C-MYC, which makes it suitable as an effective target for treatment. However, the development of such targeted active ingredients is very expensive, so in this thesis we investigate natural substances that have been used for the treatment of cancer in ancient China. We examined the substances shikonin, cnicin and artemisinin. The results show that shikonin induces apoptosis of tumor cells by reducing the expression of C-MYC and activating tumor suppressor kinase MST1. Cnicin reduces the expression of C-MYC as well, but activates MST1 only weakly. Artemisinin, on the other hand, increases expression of C-MYC and doesn't activate MST1, thus operates on inducing apoptosis of tumor cells by a completely different mechanism. (In Czech)
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