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Structural studies of transcription factors implicated in regulation of metabolism of pancreatic beta cells
Duchoslav, Vojtěch ; Maloy Řezáčová, Pavlína (advisor) ; Vaněk, Ondřej (referee)
Nkx6.1 is a homeodomain protein (37.8 kDa) and an important transcription factor, which regulates transcription of key genes in pancreatic ß-cells. Insufficient expression of this protein leads to reduced glucose uptake from blood as a consequence of suppressed transcription of the glucose transporter Glut2 and impaired glucose metabolism. Furthermore, the proliferation of pancreatic ß-cells is suppressed due to insufficient transcription of Cyclin D2, a protein regulating the mitosis. Moreover, the biosynthesis of insulin is impaired duet he diminished transcription of the genes coding for Ero1lb a Slc30a8, which as a consequence leads to reduced production of the mature insulin. Nkx6.1 could play a role in the pathogenesis of the type 2 diabetes , where ß-cells show diminished ability to compensate high demand for insulin. This malfunction is the cause of an insufficient ability to secrete insulin and death of pancreatic cells. Perhaps driven by misregulation of transcription of the genes that are involved in the mentioned processes. Nkx6.1 recognizes a strictly conserved 8-base pair DNA sequence (TTAATTAC). Its binding to DNA is regulated by an acidic domain at the C-terminus. Within the bachelor thesis, the resonances were assigned to the backbone atoms of the Nkx6.1 protein using nuclear...
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Microdomains in freshwater sediment as a driving factor in the biogeochemical processes
Duchoslav, Vojtěch ; Falteisek, Lukáš (advisor) ; Beranová, Jana (referee)
A natural arsenic anomaly at Mokrsko is a site of biogenic precipitation of realgar (As4S4) in stream sediment. The extent of the phenomenon in Mokrsko is globally unique. A previous study showed the ability of microorganisms to solubilize arsenic from its secondary minerals and to produce realgar precursors, i.e. sulfides and arsenites, by anaerobic respiration. The study also raised questions about the mechanism of realgar precipitation since physicochemical conditions favoring this reaction were never detected despite significant sampling efforts. We chemically and microbiologically analyzed sedimentary profiles to the depth of ca. 120 cm in order to understand the functioning of the biogeochemical system. The profiles comprised both the unsaturated and the saturated zone. We distinguished six different domains representing environments from the surface soil to anoxic sedimnent containing realgar-encrusted wood. An analysis of phylogenetic dissimilarity revealed that microbial communities from the various domains form distinct clusters. This suggests that different conditions prevail in the various domains, and that different biogeochemical processes take place there. Incubation (microcosm) experiments showed that bioprecipitation of realgar can be conducted in vitro. It requires a suppression...
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Bacterial role in silicate mineral alteration in near-neutral pH conditions
Duchoslav, Vojtěch ; Falteisek, Lukáš (advisor) ; Seydlová, Gabriela (referee)
It is well established that bacteria are able to catalyze dissolution of silicate minerals. Bacteria may dissolve silicates for two different purposes. They may use certain elements that can undergo redox transitions as substrates for their energetic metabolism or they can leach nutrients, that are otherwise unaccessible in their habitat. The main mechanisms of bacterially mediated silicate leaching are acidic or basic catalysis and surface complexation. The main nutrients extracted are K, Mg, P and Fe. The only element significantly exploited as substrate for dissimilative energetic metabolism is iron. In order to leach iron as a nutrient, even extremely strong complexants (i.e. siderophores) may be employed. However, only moderate complexing agents can serve to obtain iron as terminal electron acceptor. The second possibility is to reduce iron directly in the crystal grid by means of the conductive nanofibres. The oxidative dissolution of silicates by chemoautotrophs is rare, in contrast to that of sulfides. Bacterial dissolution of silicates leaves morphological and geochemical signatures, but it is still problematic to recognize and interpret them. Although it is well-known that bacteria can dissolve most of the rock-forming minerals in diverse environments we are unable to quantify their contribution...
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Biophysical characterization of the CAR/RXR protein complex with its binding partners
Duchoslav, Vojtěch ; Bouřa, Evžen (advisor) ; Pavlíček, Jiří (referee)
The constitutive androstane receptor (CAR) plays an important role as a xenosensor in the organism and is therefore widely expressed in the kidney, liver, gallbladder and in the small intestine epithelium, where the biotransformation of xenobiotic occurs. CAR is also an important factor in the elimination of bile acids and bilirubin. CAR has also been shown to have an important role in regulation of glucose and lipid metabolism. Impairment of lipid and glucose metabolism is a common cause of cardiovascular and metabolic diseases such as atherosclerosis, type 2 diabetes, obesity and insulin resistance. These diseases are called metabolic syndrome and result in severe organ damage. CAR respective its complex with RXRα (retinoid X receptor α) has become a promising biological target for drug discovery for metabolic syndrome. The major aim of this study was a structural characterization of the CAR/RXRα protein complex together with the agonist IV676*HCl, which would describe in detail the interaction of this small molecule with the receptor. Obtained structural information would be used to design improved agonists.
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Structural studies of transcription factors implicated in regulation of metabolism of pancreatic beta cells
Duchoslav, Vojtěch ; Maloy Řezáčová, Pavlína (advisor) ; Vaněk, Ondřej (referee)
Nkx6.1 is a homeodomain protein (37.8 kDa) and an important transcription factor, which regulates transcription of key genes in pancreatic ß-cells. Insufficient expression of this protein leads to reduced glucose uptake from blood as a consequence of suppressed transcription of the glucose transporter Glut2 and impaired glucose metabolism. Furthermore, the proliferation of pancreatic ß-cells is suppressed due to insufficient transcription of Cyclin D2, a protein regulating the mitosis. Moreover, the biosynthesis of insulin is impaired duet he diminished transcription of the genes coding for Ero1lb a Slc30a8, which as a consequence leads to reduced production of the mature insulin. Nkx6.1 could play a role in the pathogenesis of the type 2 diabetes , where ß-cells show diminished ability to compensate high demand for insulin. This malfunction is the cause of an insufficient ability to secrete insulin and death of pancreatic cells. Perhaps driven by misregulation of transcription of the genes that are involved in the mentioned processes. Nkx6.1 recognizes a strictly conserved 8-base pair DNA sequence (TTAATTAC). Its binding to DNA is regulated by an acidic domain at the C-terminus. Within the bachelor thesis, the resonances were assigned to the backbone atoms of the Nkx6.1 protein using nuclear...
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|
|
Microdomains in freshwater sediment as a driving factor in the biogeochemical processes
Duchoslav, Vojtěch ; Falteisek, Lukáš (advisor) ; Beranová, Jana (referee)
A natural arsenic anomaly at Mokrsko is a site of biogenic precipitation of realgar (As4S4) in stream sediment. The extent of the phenomenon in Mokrsko is globally unique. A previous study showed the ability of microorganisms to solubilize arsenic from its secondary minerals and to produce realgar precursors, i.e. sulfides and arsenites, by anaerobic respiration. The study also raised questions about the mechanism of realgar precipitation since physicochemical conditions favoring this reaction were never detected despite significant sampling efforts. We chemically and microbiologically analyzed sedimentary profiles to the depth of ca. 120 cm in order to understand the functioning of the biogeochemical system. The profiles comprised both the unsaturated and the saturated zone. We distinguished six different domains representing environments from the surface soil to anoxic sedimnent containing realgar-encrusted wood. An analysis of phylogenetic dissimilarity revealed that microbial communities from the various domains form distinct clusters. This suggests that different conditions prevail in the various domains, and that different biogeochemical processes take place there. Incubation (microcosm) experiments showed that bioprecipitation of realgar can be conducted in vitro. It requires a suppression...
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Bacterial role in silicate mineral alteration in near-neutral pH conditions
Duchoslav, Vojtěch ; Falteisek, Lukáš (advisor) ; Seydlová, Gabriela (referee)
It is well established that bacteria are able to catalyze dissolution of silicate minerals. Bacteria may dissolve silicates for two different purposes. They may use certain elements that can undergo redox transitions as substrates for their energetic metabolism or they can leach nutrients, that are otherwise unaccessible in their habitat. The main mechanisms of bacterially mediated silicate leaching are acidic or basic catalysis and surface complexation. The main nutrients extracted are K, Mg, P and Fe. The only element significantly exploited as substrate for dissimilative energetic metabolism is iron. In order to leach iron as a nutrient, even extremely strong complexants (i.e. siderophores) may be employed. However, only moderate complexing agents can serve to obtain iron as terminal electron acceptor. The second possibility is to reduce iron directly in the crystal grid by means of the conductive nanofibres. The oxidative dissolution of silicates by chemoautotrophs is rare, in contrast to that of sulfides. Bacterial dissolution of silicates leaves morphological and geochemical signatures, but it is still problematic to recognize and interpret them. Although it is well-known that bacteria can dissolve most of the rock-forming minerals in diverse environments we are unable to quantify their contribution...
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