Parkinson disease (PD) is the most common movement disorder and the second most common neurodegenerative disease. PINK1, PTEN-induced kinase 1, functions as a serine/threonine kinase as well as a protector of mitochondrial function. Mutations in PINK1 gene result in either mitochondria dysfunction or disruption of kinase signaling pathways involved in the pathogenesis of PD. In this thesis, oxidative stress levels were examined in the brain of PINK1 knockout mice, and also how heme oxygenase-1 and biliverdin reductase are affected in brain of PINK1 knockout mice. In addition, posttranslational modifications are a way to control the behavior of proteins, so posttranslational modifications of the brain of PINK1 knockout mice, including both oxidative modification and phosphorylative modification, were examined.

In this dissertation a novel approach to protein-ligand docking is presented. First an existing method to predict putative active sites is employed. These predictions are then used to cut down the search space of an algorithm that uses the fast Fourier transform to calculate the geometrical and electrostatic complementarity between a protein and a small organic ligand. A simplified hydrophobicity score is also calculated for each active site. The docking method could be applied either to dock ligands in a known active site or to rank several putative active sites according to their biological feasibility. The method was evaluated on a set of 310 protein-ligand complexes. The results show that with respect to docking the method with its initial parameter settings is too coarse grained. The results also show that with respect to ranking of putative active sites the method works quite well.

Claims arising from invalid employment termination Abstract in English language The goal of this Master thesis is to discuss and analyse the law and case law surrounding invalid employment termination and claims arising from such disputes. An unseparable part of this issue is the distinction whether such an action taken by a party is valid, invalid, or putative. In the introducion i describe the goals and themes of this Master thesis in more detail. In the first chapter I describe employment itself, it's features and it's importance in the context of Labour Code. I also discuss the difference between it and other types of labour contracts, and I try to find an answer to why there is such a few cases of parties pursuing legal action in response in invalid termination of these contracts. The second chapter contains the ways employment can be lawfully terminated, where I focus primarily on unilateral termination. I describe the relatively uncomplicated mutually agreed employment termination, dismissal both from the employer's end and the employee's end, including all legal grounds for dismissal. Then I briefly describe severance pay, an important claim of the employee. The next subchapter deals with immediate termination of employment, within the duration of probatory period or not, with emphasis on the...

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The human gamma-delta (gd) TCR+ T-cell subset may undergo specific antigen-driven activation and clonal expansion, in the context of systemic sclerosis (SSc) pathogenesis. The purpose of this study was; 1) To determine whether gd TCR+ T-cells are clonally expanded in skin biopsies and peripheral blood from patients with SSc; and 2) To develop approaches for identification of the antigens recognized by these clonally-expanded gd TCR+ T-cells. Total RNA was isolated from the skin biopsies and peripheral blood of patients with SSc (n=8). After cDNA synthesis, the g- and d-chain TCR transcripts were amplified by PCR, cloned and sequenced for analysis. Full length copies of the TCR transcripts were constructed, expressed in a TCR-negative Jurkat T-cell line using retroviral gene transduction, and verified by RT-PCR and flow cytometry for gd TCR expression. Putative antigen recognition, by the transduced gd TCR+ Jurkat T-cell lines, was assessed via; 1) Measuring intracellular calcium flux in the transduced cells after stimulation with putative SSc antigens, including DNA topoisomerase I, centromere proteins A and B, hsp 27, hsp 90 and the viral lysate of human cytomegalovirus; and 2) Cytotoxicity against human endothelial cell lines (HUVEC and HLMVEC) via measurement of lactate dehydrogenase release from the targets. We report the presence of substantial, statistically-significant, proportions of identical g- and d-chain transcripts in skin biopsies and PBMC of patients with SSc, demonstrating the presence of antigen-driven clonal expansions. Jurkat T-cells, transduced with the clonally-expanded gd TCR transcripts from a patient, showed no evidence of cytotoxicity against the human endothelial cell lines, or calcium flux in response to stimulation with the putative SSc antigens assessed. In conclusion, extensive clonal expansions of g- and d-chain TCR transcripts were identified in skin biopsies and peripheral blood of patients with SSc, demonstrating the presence of oligoclonal populations of gd TCR+ T-cells in these patients. These gd TCR+ T-cells have undergone proliferation and clonal expansion in vivo in response to as yet unidentified antigens. Furthermore, an approach has been developed for the identification of the antigens recognized by the clonally-expanded gd TCR transcripts, which can be expanded to additional patients with SSc. / Microbiology and Immunology

"Mémoire présenté à la Faculté des études supérieures en vue de l'obtention du grade de maîtrise en Droit option Droit, Biotechnologies et Société" / L'A.D.N. détermine toute fonction nécessaire à la VIe humaine. Les tests d'A.D.N. peuvent identifier presque tous les êtres humains. Exacts et fiables, ces tests ne nécessitent qu'un échantillon minime d'A.D.N. Ils ont chamboulé, non seulement la science, mais aussi le droit. Lorsque ces tests sont utilisés dans un but d'identification génétique (contrairement à un but médical), ceux-ci peuvent établir définitivement des liens filiaux. Comment le droit civil québécois détermine le meilleur intérêt de l'enfant lorsque des tests de paternité sont utilisés comme moyens de preuve de la filiation d'un enfant? Le meilleur intérêt de l'enfant est un concept-clé dans le droit civil québécois. Les règles régissant la filiation légale et la hiérarchie des moyens de preuve pour cette filiation sont aussi affectées. Une étude du droit civil québécois révèle différentes approches afin de déterminer le meilleur intérêt de l'enfant dans les cas de paternité: 1) l'approche de la primauté de la stabilité socio-affective de l'enfant, 2) celle de la primauté de la vérité biologique de l'enfant, et 3) celle dite «personnalisée». L'approche personnalisée pourrait être la plus adaptée puisqu'elle traite chaque enfant comme une personne à part, considère tous les facteurs dans sa vie et pèse les différentes relations entre les parties. L'approche semble répondre aux besoins et à la situation de chaque enfant comme personne unique. / DNA determines all functions necessary to human life. DNA tests can identify almost every human being. Accurate and reliable, these tests need only a minimal quantity of DNA. They have changed radically not only science, but also the law. When used for genetic identification purposes (as opposed to medical), they can establish definitely filial links. How does Québec's civil law determine the best interests of the child when DNA paternity tests are offered as proof of the filiation of a child? The best interests of the child are a key concept in the civil law of Québec. The rules establishing legal filiation and the hierarchy of proof within are also affected. A study of Québec case law reveals different approaches in determining the best interests of the child in paternity cases: 1) the approach preferring the primacy of socio-affective stability of the child, 2) the approach preferring the primacy of biological truth, and, 3) the personalized approach. The personalized approach may be the most appropriate since it treats each child as unique, considers every factor in his or her life and weighs aIl the different relationships between parties. This approach seems to provide for the needs and situation of every child as an individual.

Claims arising from invalid termination of employment Abstract The aim of this Master thesis is to analyse legislation concerning the invalid employment termination, to distinguish the invalid employment termination from putative employment termination established by Act No. 89/2012 Coll., Civil Code, as amended, and especially to summarize the legislation and case law concerning claims arising from invalid employment termination. The introductory chapter contains the aims of this thesis and represents the reasons why I think this topic is still relevant. Chapter two explains the employment briefly. Chapter three provides the brief introduction to employment termination and individual subchapters present the essentials of individual types of employment termination. Chapter four analyses invalid employment termination, and relation between the Civil Code and Labour Code and defines conditions necessary to qualify the employment termination as the act. Subchapter two analyses putative employment termination and its results in employment termination field. Subchapter three concerns the invalid employment termination, distinguishes between the void termination and voidable termination and represents its grounds. Chapter five summarizes selected aspects of court proceeding. Particular subchapters therefore...

Flavonoids are a group of plant secondary metabolites that are vital to the cell systems of plants. The intake of these chemicals is advantageous to animals for their antioxidant properties that affect the function of immune and inflammatory cells. The bitter taste of grapefruit (Citrus paradise) and other citrus species is caused by the accumulation of glycosylated flavonoids. Glucosyltransferases (GTs) are enzymes that add glucose moieties to a carbon or hydroxyl group of natural products. The function of a putative secondary product GT clone was tested. In previous research, putative GT 4 was cloned into a pCD1 modified pET expression system, heterologously expressed in E.coli, and screened for activity with only a few substrates, and little GT activity was found. Issues of protein localized to inclusion bodies in bacteria are being addressed. PGT 4 is being heterologously expressed in yeast (Pichia pastoris) to allow for protein production and analysis. PGT 4 will be screened for GT activity with different flavonoid subclass representatives and simple phenolics. PGT 4’s significant impact on the biochemical regulation of Citrus paradise will be elucidated with its characterization and determination of PGT 4’s structure and function.

Flavonoids are a group of plant secondary metabolites that are vital to the cell systems of plants. The intake of these chemicals is advantageous to animals for their antioxidant properties that affect the function of immune and inflammatory cells. The bitter taste of grapefruit (Citrus paradisi) and other citrus species is caused by the accumulation of glycosylated flavonoids. Glucosyltransferases (GTs) are enzymes that add glucose moieties to a carbon or hydroxyl group of natural products. The function of a putative secondary product GT clone was tested. In previous research, putative GT 4 was cloned into a pCD1 modified pET expression system, heterologously expressed in E.coli, and screened for activity with a few substrates; little GT activity was found. Issues of protein localized to inclusion bodies in bacteria were addressed. PGT 4 is being heterologously expressed in yeast (Pichia pastoris) to allow for protein production and analysis. PGT 4 was screened for GT activity with different flavonoid subclass representatives and simple phenolics.

L'A.D.N. détermine toute fonction nécessaire à la VIe humaine. Les tests d'A.D.N. peuvent identifier presque tous les êtres humains. Exacts et fiables, ces tests ne nécessitent qu'un échantillon minime d'A.D.N. Ils ont chamboulé, non seulement la science, mais aussi le droit. Lorsque ces tests sont utilisés dans un but d'identification génétique (contrairement à un but médical), ceux-ci peuvent établir définitivement des liens filiaux. Comment le droit civil québécois détermine le meilleur intérêt de l'enfant lorsque des tests de paternité sont utilisés comme moyens de preuve de la filiation d'un enfant? Le meilleur intérêt de l'enfant est un concept-clé dans le droit civil québécois. Les règles régissant la filiation légale et la hiérarchie des moyens de preuve pour cette filiation sont aussi affectées. Une étude du droit civil québécois révèle différentes approches afin de déterminer le meilleur intérêt de l'enfant dans les cas de paternité: 1) l'approche de la primauté de la stabilité socio-affective de l'enfant, 2) celle de la primauté de la vérité biologique de l'enfant, et 3) celle dite «personnalisée». L'approche personnalisée pourrait être la plus adaptée puisqu'elle traite chaque enfant comme une personne à part, considère tous les facteurs dans sa vie et pèse les différentes relations entre les parties. L'approche semble répondre aux besoins et à la situation de chaque enfant comme personne unique. / DNA determines all functions necessary to human life. DNA tests can identify almost every human being. Accurate and reliable, these tests need only a minimal quantity of DNA. They have changed radically not only science, but also the law. When used for genetic identification purposes (as opposed to medical), they can establish definitely filial links. How does Québec's civil law determine the best interests of the child when DNA paternity tests are offered as proof of the filiation of a child? The best interests of the child are a key concept in the civil law of Québec. The rules establishing legal filiation and the hierarchy of proof within are also affected. A study of Québec case law reveals different approaches in determining the best interests of the child in paternity cases: 1) the approach preferring the primacy of socio-affective stability of the child, 2) the approach preferring the primacy of biological truth, and, 3) the personalized approach. The personalized approach may be the most appropriate since it treats each child as unique, considers every factor in his or her life and weighs aIl the different relationships between parties. This approach seems to provide for the needs and situation of every child as an individual. / "Mémoire présenté à la Faculté des études supérieures en vue de l'obtention du grade de maîtrise en Droit option Droit, Biotechnologies et Société"