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Microarray Data Interpretation
Ludwig, Petr ; Šilhavá, Jana (referee) ; Smrž, Pavel (advisor)
This Bachelor thesis explains the basics of biochip or microarray data interpretation, starting with short introduction to genetics, especially genetic information significance evaluating. The focus was set mainly on the set of scripts transforming and analyzing the sample data. The data used in this thesis are a result of biochip analysis of the Colon Tumor tissues. The secondary result represents disclosing the main marker for this particular type of cancer, the primary result is evaluation of marker significance in the context of signaling pathways. The resulting pathways are sorted by relevance.
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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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Interaction between herbivores and pathogens on plant
Nerandžičová, Denisa ; Koubek, Tomáš (advisor) ; Weiser, Martin (referee)
Plants are often simultaneously attacked by herbivores and phytopathogens and interactions between these antagonists have consequences for their fitness and also for plant defense. Plant disease leads to modification of plant biochemical processes which alter the host plant choice by herbivores and the availability of their nutritional resources and it induces changes in plant defense responses. Herbivores facilitate the development of plant diseases and their transmission from plant to plant. Mutual antagonism between jasmonic acid and salicylic acid signaling pathways is believed to be the main cause behind the effects of the interactions. However, according to diverse outcomes from current studies, this theory seems to be oversimplified and thus inapplicable. Effects of the interactions are driven by many more factors, from which the species specificity plays the main role. Despite this, current literature accumulates evidence that these interactions do not multiply damage from the double attack. Subsequent damage is usually more severe within individual organs but is much less severe for overall plant fitness due to the plant's ability to compensate for the losses.
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Evolution of the gene regulatory network underlying the formation of the gastrula organizer
Macháčová, Simona ; Kozmikova, Iryna (advisor) ; Krylov, Vladimír (referee) ; Buchtová, Marcela (referee)
During gastrulation, the vertebrate embryo is organized from the clump of cells into a bilaterally symmetric body. This organization process is driven by the gastrula organizer. Its establishment is induced by maternal Wnt/β-catenin signaling and Nodal/Activin signaling localized in the presumptive dorsal region of the embryo. The regulative environment then triggers the expression of the organizer-specific genes which create morphogen gradients in the embryonic body and therefore give each cell positional information. However, the evolution of vertebrate organizer establishment remains vague. Here we aim to test the compatibility of the invertebrate cis-regulatory modules with the vertebrate gene regulatory network (GRN). We introduced fluorescent reporter genes under the control of the invertebrate regulatory sequence of organizer-specific genes into a vertebrate model to observe their behavior in the context of the vertebrate GRN. We found and functionally verified a 500 bp-long amphioxus sequence (an enhancer) that is necessary and sufficient to drive a correct Chordin gene expression in the gastrula organizer in zebrafish. Chordin is a prominent organizer-specific gene antagonizing Bone Morphogenetic Protein (BMP) signaling. We tested also other invertebrate genes for their compatibility with...
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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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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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Role of CD8- and CD4-Lck interactions in the signaling and development of T cells.
Horková, Veronika
Adaptive immune response plays a key role in maintaining homeostasis of the organism. T cells use an immense repertoire of T-cell receptors (TCRs) to discriminate between self and foreign antigens with very high sensitivity. Although we have many clues outlining how an ideal TCR repertoire is selected, and a good understanding of the TCR signaling machinery, there are still some key aspects of these processes that remain controversial. The objective of this thesis is to extend our knowledge of the very proximal events of TCR signaling, with special focus on interaction of TCR coreceptors with lymphocyte-specific kinase LCK. Coreceptor-LCK interaction has been described to regulate several aspects of T- cell development and response. We observed dynamic change of this interaction in course of T-cell development. Interestingly, CD4 and CD8 coreceptors displayed differential dynamics of interaction with LCK. Our data suggest that such disparity in coreceptor- LCK interaction leads to selection of more self-reactive TCR repertoire in CD8+ T cells. Moreover, when the highly self-reactive CD8+ T cells get to the periphery, the homeostatic signals drive their differentiation towards a more tolerogenic memory-like phenotype. To finally resolve the role of coreceptor-LCK interaction in the T-cell...
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Role of CD8- and CD4-Lck interactions in the signaling and development of T cells.
Horková, Veronika ; Štěpánek, Ondřej (advisor) ; Černý, Jan (referee) ; Hons, Miroslav (referee)
Adaptive immune response plays a key role in maintaining homeostasis of the organism. T cells use an immense repertoire of T-cell receptors (TCRs) to discriminate between self and foreign antigens with very high sensitivity. Although we have many clues outlining how an ideal TCR repertoire is selected, and a good understanding of the TCR signaling machinery, there are still some key aspects of these processes that remain controversial. The objective of this thesis is to extend our knowledge of the very proximal events of TCR signaling, with special focus on interaction of TCR coreceptors with lymphocyte-specific kinase LCK. Coreceptor-LCK interaction has been described to regulate several aspects of T- cell development and response. We observed dynamic change of this interaction in course of T-cell development. Interestingly, CD4 and CD8 coreceptors displayed differential dynamics of interaction with LCK. Our data suggest that such disparity in coreceptor- LCK interaction leads to selection of more self-reactive TCR repertoire in CD8+ T cells. Moreover, when the highly self-reactive CD8+ T cells get to the periphery, the homeostatic signals drive their differentiation towards a more tolerogenic memory-like phenotype. To finally resolve the role of coreceptor-LCK interaction in the T-cell...
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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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The role of growth factors and cytokines in regulation of mammalian oocyte maturation
Marcollová, Kateřina ; Procházka, Radek (advisor) ; Vávra, Jiří (referee)
Reproduction is key for species survival. Oocytes are blocked in prophase I of meiosis in follicle. Gonadotropin stimulation leads to follicle growth and competent oocyte. First polar body extrusion is a sign of meiotic division resumption. Oocyte is blocked at prophase I by a high cAMP level, activating PKA, that inhibits MPF. CNP binds to NPR2, that stimulates the generation of cGMP in granulosa cells, which diffuses to oocyte where it competes with cAMP on PDE3A. LH and FSH released from pituitary gland initiates signaling cascade restoring meiotic division. Synthesis of AREG, EREG and BTC activates EGFR and MAPK pathways in somatic cells which contribute to reduction of gap junction permeability, lowering NPR2 activity, that leads to reduction of cGMP production and transport. Less cGMP diffuses to oocytes, which leads to PDE3A activation and cAMP hydrolysis. This causes MPF activation and meiotic division resumption. MAPK together with PI3K participate on increasing production of hyaluronic acid, thereby cumulus cells expansion and oocyte ovulation. Oocyte maturation and growth is improved with utilization of in vitro technics and oocyte cultivation with growth factors and cytokines. FLI medium, combining FGF2, LIF and IGF-1, increases oocyte cultivation success and blastocyst quality of farm...
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