Master of Science / Division of Biology / Revathi Govind / Toxigenic Clostridium sordellii causes uncommon but highly lethal infections in humans and animals. Recently, an increased incidence of C. sordellii infections has been reported in women undergoing obstetric interventions. Pathogenic strains of C. sordellii produce numerous virulence factors, including sordellilysin, phospholipase, neuraminidase, and two large clostridial glucosylating toxins, TcsL and TcsH. Recent studies have demonstrated that TcsL toxin is an essential virulence factor for the pathogenicity of C. sordellii. In this study, we identified and characterized TcsR as the toxin gene (tcsL) regulator in C. sordellii. High-throughput sequencing of two C. sordellii strains revealed that tcsR lies within a genomic region that encodes TcsL, TcsH, and TcsE, a putative holin. By using ClosTron technology, we inactivated the tcsR gene in strain ATCC 9714. Toxin production and tcsL transcription were decreased in the tcsR mutant strain. However, the complemented tcsR mutant produced large amounts of toxins, similar to the parental strain. Expression of the Clostridium difficile toxin gene regulator tcdR also restored toxin production to the C. sordellii tcsR mutant, showing that these sigma factors are functionally interchangeable.

<p>Abstract</p><p>G-protein coupled receptors (GPCRs) are having the high medical importance since almost half of the medicinal drugs are designed as modulators of receptor molecules. Crystal structure or NMR structures of GPCRs are very difficult to determine because all GPCRs are typically bound to the cell membrane and thus their molecular activation mechanism is still unclear. The recent publication of the crystal structure of the 2-adrenoreceptor will provide new insights in the field of GPCR research.</p><p>Ghrelin is a peptide growth hormone which binds to the growth hormone secretagogue receptor (GHS-R) and stimulates the release of growth hormone. Based on the known ghrelin receptor binding core sequences wFwLL (upper letter and lower letter representative for L-form and D-form of the amino acids respectively), we prepared two novel peptide analogs with terminal S-(2-aminoethylsulfenyl) cysteine residues. These peptides were tested for their ability to suppress the binding of ghrelin to transfected COS7 cell-line (Kidney fibroblast line from the green African monkey) cells expressing the ghrelin wild-type receptor or certain mutants thereof. As a result we observed a significant reduction of the total number of binding sites accessible for ghrelin, which increased with the time the cells were incubated with our test compounds. This observations support our hypothesis that the peptides we tested form a covalent bond with free thiols located closely to the ligand binding-site of the receptor protein by disulfide thiol exchange which is an interesting target for development of anti-obesity drugs.</p>

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Abstract G-protein coupled receptors (GPCRs) are having the high medical importance since almost half of the medicinal drugs are designed as modulators of receptor molecules. Crystal structure or NMR structures of GPCRs are very difficult to determine because all GPCRs are typically bound to the cell membrane and thus their molecular activation mechanism is still unclear. The recent publication of the crystal structure of the 2-adrenoreceptor will provide new insights in the field of GPCR research. Ghrelin is a peptide growth hormone which binds to the growth hormone secretagogue receptor (GHS-R) and stimulates the release of growth hormone. Based on the known ghrelin receptor binding core sequences wFwLL (upper letter and lower letter representative for L-form and D-form of the amino acids respectively), we prepared two novel peptide analogs with terminal S-(2-aminoethylsulfenyl) cysteine residues. These peptides were tested for their ability to suppress the binding of ghrelin to transfected COS7 cell-line (Kidney fibroblast line from the green African monkey) cells expressing the ghrelin wild-type receptor or certain mutants thereof. As a result we observed a significant reduction of the total number of binding sites accessible for ghrelin, which increased with the time the cells were incubated with our test compounds. This observations support our hypothesis that the peptides we tested form a covalent bond with free thiols located closely to the ligand binding-site of the receptor protein by disulfide thiol exchange which is an interesting target for development of anti-obesity drugs.

Submitted by Viviane Lima da Cunha (viviane@biblioteca.ufpb.br) on 2017-07-18T12:41:11Z No. of bitstreams: 1 arquivototal.pdf: 2094299 bytes, checksum: 783d6f9949086fb75e4a51fc3adbd48a (MD5) / Made available in DSpace on 2017-07-18T12:41:11Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2094299 bytes, checksum: 783d6f9949086fb75e4a51fc3adbd48a (MD5) Previous issue date: 2016-04-22 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this work, new solutions based on the Boundary Element Method (BEM) are established for the linear analysis of bending and stability problems of Reddy-Bickford beams. All mathematical steps to write the BEM representation are properly presented: transformation of governing differential equations into equivalent integral equations, deduction of fundamental solutions, formation and solution of algebraic representation.In addition, elastic foundations (winkler and pasternak’s types) attached to Reddy-Bickford beams are solved by BEM as well. It is also addressed a convenient strategy for discontinuities in the area such as abrupt change in geometry of the cross section (stepped beam), intermediate axial load, intermediate supports (continuous beam). Numerical examples incorporating various types of discontinuities and boundary conditions in the field are presented to validate the solutions proposed BEM. / Neste trabalho, novas soluções, baseadas no Método dos Elementos de Contorno (MEC), são estabelecidas para a análise linear de problemas de flexão e estabilidade de barras de Bickford-Reddy. Todos os passos matemáticos para estabelecer a representação do MEC são apresentados: transformações das equações diferenciais governantes em equações integrais equivalentes, dedução das soluções fundamentais, obtenção e solução do sistema alébrico. Além disso, fundações elásticas (Winkler e Pasternak) em barras de Bickford-Reddy também são analisados pelo MEC. É também abordada uma conveniente estratégia para de discontinuidades no domínio tais como: mudança abrupta de geometria da seção transversal (viga escalonada), carga axial intermediária, apoios rígidos no domínio (viga contínua). Exemplos numéricos incorporando vários tipos de condições de contorno e discontinuidades no domínio são apresentadas para validar as soluções do MEC propostas.

The present research is carried out from the viewpoint of primarily space applications where human lives may be in danger if they are to work under these conditions. This work proposes to develop a one-degree-of-freedom (1-DOF) force-reflecting manual controller (FRMC) prototype for teleoperation, and address the effects of time delays commonly found in space applications where the control is accomplished via the earth-based control stations. To test the FRMC, a mobile robot (PPRK) and a slider-bar were developed and integrated to the 1-DOF FRMC. The software developed in Visual Basic is able to telecontrol any platform that uses an SV203 controller through the internet and it allows the remote system to send feedback information which may be in the form of visual or force signals. Time delay experiments were conducted on the platform and the effects of time delay on the FRMC system operation have been studied and delineated.

M.A. / This study attempts to trace the interrelationship between literature and its historical contexts in six stories by South African women writers. Six South African writers have been selected because their work foregrounds the theme of oppression and because they are representative of the different groupings of the South African population. In her story "The Sisters", Pauline Smith explores the silencing effects of gender oppression in a patriarchy. In "The Apostasy of Carlina", Bertha Goudvis writes of women-on-women oppression between the white and black races. Jayapraga Reddy explores the complexities of intercultural relationships in "Friends". In "Let Them Eat Pineapples", Lizeka Mda explores the oppressive effects of industrial-development on the tribal system in Transkei. In "Last Look at Paradise Road", Gladys Thomas, like Goudvis before her, focuses on the racial discrimination practised by whites against blacks. Gcina Mhlope reveals women-on-women oppression practised both by white-on-black and black-on-black. A chronological ordering of these short stories reveals certain changes in the extent to which attitudes to oppression are revealed and criticized. This study suggests that while there has not been a significant decrease in the degree of oppression to which South African women have been subjected, the increasing awareness and exposure of gender oppression suggests the promise of self-actualization in the struggle for democracy in South Africa.