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Mechanistic insights into alcohol-induced interstrand crosslink repair by the nuclease SLX4-XPF-ERCC1
Havlíková, Jana ; Šilhán, Jan (advisor) ; Lux, Vanda (referee)
Alcohol ranks among the most widely used recreational drugs in the world, even though it is considered a risk factor for more than 200 diseases. The primary negative impact of alcohol lies in its metabolite, acetaldehyde, which, as a highly reactive compound, can form mutagenic adducts and interstrand crosslinks (ICLs) in DNA. The formation of ICLs, which have a covalent nature and block the separation of the two DNA strands during replication, is one of the important causes of mutagenesis and carcinogenesis. To maintain genomic stability, repair mechanisms have evolved. One of them is a pathway that uses proteins encoded by Fanconi anaemia genes, whose defects lead to the disease of the same name. Defects in repair pathways can be particularly dangerous in individuals with impaired functionality in other metabolic pathways, such as alcoholics and individuals with mutations in genes that result in the accumulation of toxic acetaldehyde. The theoretical part of this thesis deals with alcohol metabolism, in vivo acetaldehyde formation, and its interactions with DNA. The ICL and their repair pathways are characterized in more detail. A separate chapter is dedicated to Fanconi anaemia. The practical part of this work focuses on the preparation of site-specific acetaldehyde- induced ICL (AA-ICLs) and the study...
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Látky vázající oxid siřičitý ve víně
Musil Petrjánošová, Martina
This bachelor thesis deals with the description of the characteristics of sulfur dioxide, its properties, influence on organoleptic properties and its use with respect to human health. In addition to sulfur dioxide, the work also deals with substances that bind it in wine, such as acetaldehyde, ketonic acids - pyruvic acid and acid 2-oxoglutar et al. Describes the effect of sulfur on the formation of these compounds. At the end of the thesis, the effects of sulfur dioxide on human health and legislation, from which the limits for its use and labeling are based, are presented.
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Studium fyzikálně-chemických vlastností plodů broskví a švestek
Joklová Kaňová, Jana
Dissertation thesis Study of physical chemical features in fruits of peaches and plums was developed at the Institute of Post Harvest Technology of Horticulture Products at Faculty of Horticulture of Mendel University in Brno. This thesis concentrated on setting of material elements in fruits of peaches, the variety 'Red Haven' in the period of ripening and post-harvest storage in different types of atmosphere according to contents of CO2 and O2. In five analysed varieties of peaches 'Flamingo', 'Harbele', 'Harblaze', 'Harbrite', and 'Maria Marta' were set ripening values during ripening on tree. In varieties of plum fruits 'Valjevka', 'President', 'Stanley' was found their tolerance against gas mixtures. During ripening of peach varieties were set volatile elements (ethanol, acetaldehyde) and was stated the concentration of ethylene in the critical period of ripening. In literary review there are characterized material elements of pulp fruits, both chemical structure of fruits, and volatile aromatic substances and their biogenesis, there are described in detail material substances of fruits, amongst which belong biological, physical, sensory, technological signs of quality and post harvest influences on fruits. Further ethylene is characterized in post-harvest period and its physiological features and methods of its effect limitation, factors of plant reaction against ethylene, and chemical inhibition of ethylene reception. Next part deals with methods of quality evaluation and techniques of fruit storage, further on with fruits of plums, peaches and their general characteristics. Experimental part evaluates several fractional methodics. Assessment of peach varieties in three stages of ripening and setting of ripening index, influence of low content of oxygen on production of anaerobic metabolites and volatile materials stated in plum fruits, distribution of frequency of peach fruits ripening on tree in five stages of ripening, production of ethylene according to the grades of ripening in peach varieties, their sensory evaluation and setting of volatile aromatic compounds. In variety 'Red Haven' there were evaluated grades of ripening in the range: unripe to over ripe, which represented in dates five successive harvests. Each successive term was compiled of 40 fruits of average weight for the set grade of ripening. Production of ethylene was evaluated through distribution of fruits in settled harvest date, and was distinctively different in fruit distribution according to ethylene content pursuant to harvest date. In executed measurements of fruits of peach variety 'Red Haven' ripening on tree in grades of ripening unripe, ripe, over ripe, in their frequency five to seven there was stated concentration of ethanol and acetaldehyde expressed in mg*l-1 by direct spraying of juice into filling analytic colon. Concentration of acetaldehyde did not change during fruit ripening, and this metabolite can be assessed as interim which changed by alcohol dehydrogenase into ethanol. Concentration of ethanol in over ripe fruits is characteristic with higher content which does not represent multiple concentrations in over ripening in common oxygenated atmosphere. Evaluation was executed only in one variety, however, similar tendencies should be supposed in other varieties as well. Index of ripening (IZ = RS* strength/TK) was formulated in five peach varieties, which represents processes of fruit ripening on tree and important differences were found for ripe and unripe fruits, whereas index of ripening between ripe and over-ripe fruits differs only in several units. With following ripening rates in varieties there were determined differences in phases unripe to ripe for varieties 'Harblaze' and 'Maria Marta'. Furthermore these varieties were evaluated by sensory analysis as well. In analytical method HP/GC/MS 42 volatile aromatic compounds were specified in groups of alcohols, aldehydes, esters, terpenes, lactones, and organic acids in plum fruits in varieties 'Valjevka' and 'Stanley'. In Tukey´s test productions of each specified volatile compounds were evaluated. In variety 'Red Haven' treated with four different gas mixtures (ULO, CA, RA, FAN) according to percentage of content of set amount of CO2 and O2, and stored in these atmospheres during 29 days, there were specified several volatile aromatic materials through analytical method HP/GC/MS.
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Molecular mechanisms of carcinogenic effects of alcohol
Vepřková, Jana ; Kábelová, Adéla (advisor) ; Novotná, Božena (referee)
Alcohol (ethanol) enters the human body mainly through ingestion of alcoholic beverages and its chronic consumption is considered a worldwide socio-economic problem. Besides others, alcohol consumption increases the risk of development of breast, liver, colorectal and upper aerodigestive tract cancer. In the liver, ethanol is metabolised into toxic acetaldehyde which is the main cause of DNA damage leading to cancer development. Acetaldehyde covalently interacts with nucleotides in the DNA forming DNA adducts such as N2 -ethylidene-2'-deoxyguanosine or S- and R-α-methyl-γ-hydroxy-1,N2 - propano-2′-deoxyguanosine. Acetaldehyde can also interact with proteins and disrupt their function. Ethanol metabolism by cytochrome P450 2E1 leads to production of reactive oxygen species, that subsequently damage cellular molecules such as lipides and DNA. Ethanol also initiates carcinogenesis through aberant DNA methylation or interference with retinoic acid metabolism. In cancer development, alcohol interacts with other environmental and genetic factors, which can increase the risk of developing cancer in predisposed individuals.
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Vliv síření vína na vznik sloučenin vázajících oxid siřičitý ve víně
Sikora, Jakub
This thesis is concerned with the formation of carbonyl compounds in wine, depending on the spread of wine. Therefore examines what influences the spread of musts and wines on the formation of carbonyl compounds. Discusses the characteristics and forms of sulfur dioxide. Further detail the carbonyl compounds which bind just with sulfur dioxide. In this work it was found that the influence of the spread of the wine has no great influence formation of carbonyl compounds. On the contrary, it was confirmed that the initial SO2 concentration in the must greatly affects the formation of acetaldehyde, which binds sulfur dioxide. Furthermore ratified the greater influence on the formation of carbonyl compounds, the activity of microorganisms in the wine than different concentrations of SO2.
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Vliv síření na vznik sloučenin vázajících SO2 ve víně
Holka, Andrej
The thesis focuse on the effect of dose levels of sulfur dioxide in the must on the formation of carbonyl compounds. Futhermore it is concerned with oenological properties of sulfur dioxide, its forms and effects on wine. The thesis corroborates in detail carbonyl compounds bind sulfur dioxide and discusses their origin and various options to affect their quantity. Substances that may partially replace sulfur dioxide and thereby reduce its total quantity in wine are also debated. Experimental part of the thesis involved samples of wine differing in quantity of sulfur dioxide added to the must before fermentation and in forms of nutrition. Using the HPLC analysis concentrations of acetaldehyde, pyruvic acid, and 2-oxoglutaric acid were determined. The experiment demonstrated the effect of initial doses of sulfur dioxide on the amount of generated acetaldehyde and pyruvic acid. The effect of addition of thiamine, which reduces formation of pyruvic acid, was also shown.
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