Abstract Lysyl hydroxylase (LH) catalyzes the post-translational formation of hydroxylysines in collagens and collagenous proteins. Three lysyl hydroxylase isoforms, LH1, LH2 and LH3, have been identified from different species. In addition, LH2 has two alternatively spliced forms, LH2a and LH2b. The hydroxylysines have an important role in the formation of the intermolecular collagen crosslinks that stabilize the collagen fibrils. Some of the hydroxylysine residues are further glycosylated. In this thesis the substrate amino acid sequence specificities of the LH isoforms were analyzed using synthetic peptide substrates. The data did not indicate strict amino acid sequence specificity for the LH isoforms. However, there seemed to be a preference for some sequences to be bound and hydroxylated by a certain isoform. Galactosylhydroxylysyl glucosyltransferase (GGT) catalyzes the formation of glucosylgalactosylhydroxylysine. In this study, LH3 was shown to be a multifunctional enzyme, possessing LH and GGT activities. The DXD-like motif, characteristic of many glycosyltransferase families, and the conserved cysteine and leucine residues in the N-terminal part of the LH3 molecule were critical for the GGT activity, but not for the LH activity of the molecule. The GGT/LH3 protein level was found to be decreased in skin fibroblasts and in the culture media of cells collected from members of a Finnish epidermolysis bullosa simplex (EBS) family, which was earlier reported to have a deficiency of GGT activity. In this study, we showed that the reduction of enzyme activity is not due to a mutation or lower expression of the LH3 gene. Our data indicate that the decreased GGT/LH3 activity in cells has an effect on the deposition and organization of the key extracellular matrix components, collagen types VI and I and fibronectin, and these changes are transmitted to the cytoskeletal network. These findings underline LH3 as an important extracellular regulator.

of thesis Diagnostics of neuroinfection caused by human herpesviruses using nucleic acid amplification methods author: MUDr. Klára Labská supervisor: doc. MUDr. Vilma Marešová, CSc. In recent years, the diagnosis of neuroinfections has undergone a shift towards molecular biology methods. Our research focused on the predictive value of the capture of herpesvirus (HV) DNA in cerebrospinal fluid. In the first study, we examined the presence of DNA neurotropic herpes viruses (HSV1, HSV2, VZV and HHV6) in cerebrospinal fluid in immunocompetent patients with laboratory-confirmed tick-borne meningoencephalitis and enterovirus meningitis and meningoencephalitis. The control group consisted of patients with proven absence of an inflammation in the cerebrospinal fluid. Patients were followed for 6 months. The course of the disease and its consequences, including laboratory tests, were compared between groups of patients with and without the presence of HV DNA. In the second study, we tried to demonstrate the presence of HSV1 DNA in cerebrospinal fluid during its symptomatic reactivation in patients with purulent meningitis. In our group of immunocompetent patients with non-purulent inflammation in the cerebrospinal fluid, the proportion of HV DNA positive patients reached 7.5% (13 out of 173), we also...

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Master‘s thesis deals with the theory of distributed optimization programs (next time just DOP), the suggestion and programme sample solver DOP and verification of the functionality of DOP ideas, principles and system architecture.

Orientador: João Peres Vieira / Resumo: A Programação Linear é usada na Pesquisa Operacional para resolução de problemas cujo objetivo é encontrar a melhor solução para aqueles problemas que tenham seus modelos representados por expressões lineares. A Álgebra Linear vai ser a ferramenta para a Programação Linear, resolvendo problemas de maximização ou minimização. Vamos utilizar o Método Simplex e, no caso de duas variáveis, apresentaremos também o método gráfico. / Abstract: Linear Programming is used in Operational Research to solve problems resolution whose goal is to find the best solution for those problems that have their models represented by linear expressions. Linear Algebra will be the tool for Linear Programming, solving maximization or minimization problems. We will use the Simplex Method and, in the case of two variables, we will also present the graphical method. / Mestre

Purpose of Review: Recent technological developments have vastly improved our ability to study the host microbiome and its role in many disease states. Numerous other reviews have contributed to our understanding of single viruses and gut microbiota or immunological outcomes. Here, we report, in aggregate, the newest data on genital microbiota interactions with the three most common viral STIs. Recent Findings: Four themes emerge: (1) the repeatability of specific community state types corresponding with infection risk, (2) a role for the microbiota as both therapeutic target and major player in treatment efficacy, (3) a need for models in which to study the mechanisms at play in microbiota/virus interactions, and (4) the impact of microbiota populating external genitalia on viral transmission. Summary: The studies reviewed herein suggest a convoluted interplay between host microbiota and viral STIs. More mechanistic studies are needed in order to leverage these interactions to improve prevention and treatment strategies.

The purpose of this investigation was to observe changes induced by types 1 and 2 herpes simplex viruses (HSY 1 and HSY 2) when these viruses were cultivated in fish 2 cells. The possibility of attempting to use human strains of herpesviruses in order to transform normal fish tissue culture preparations was considered. Three different fish cell cultures were tested: CHSE-214 cell lines were derived from embryonic chinook salmon (Oncorhynohus tshawytscha), and STE-137 cell lines were obtained from embryonic steelhead trout (Salmo gairdneri). Cells isolated from immature ovaries of rainbow trout (Salmo gairdneri) were propagated by the investigator in these studies. Both HSV 1 and HSV 2 demonstrated cytopathic effects on the 3 different cell types described above when these cells were observed during the exponential growth phase. If virus was added before cells were dividing actively, or when the cells were maintained in a stationary phase of growth, no effect was observed. Several methods were employed in an attempt to trans- form fish cells grown in tissue culture. Different quantities of live virus, preparations of ultraviolet light in- activated virus and purified viral DNA were used in these studies but malignant conversion by known viral components was not achieved. In these experiments, the 2B strain of cells obtained originally from immature ovaries of rainbow trout appeared to undergo spontaneous transformation thereby becoming established as a permanent cell line. To date tissue cultures designated 2B have undergone 25 transfers in this laboratory.

京都大学 / 0048 / 新制・課程博士 / 博士(情報学) / 甲第19417号 / 情博第596号 / 新制||情||104(附属図書館) / 32442 / 京都大学大学院情報学研究科知能情報学専攻 / (主査)教授 山本 章博, 教授 黒橋 禎夫, 教授 鹿島 久嗣, 准教授 Cuturi Marco / 学位規則第4条第1項該当 / Doctor of Informatics / Kyoto University / DFAM

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