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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

Characterization and expression of the multicatalytic proteasesubunit(26S proteasome) during the reproductive cycle of the Shrimp(Metapenaeus ensis)

Shek, Wing-kit., 石永結. January 2004 (has links)
published_or_final_version / abstract / toc / Zoology / Master / Master of Philosophy
32

Novel inhibitors of human leukocyte proteinase 3

Du, Bingfan 05 1900 (has links)
Chronic obstructive pulmonary disease (COPD) is a multifactorial disorder that is associated with an influx of macrophages, neutrophils and T-lymphocytes to the lungs and the extracellular release of several proteases, including serine (proteinase 3, elastase, cathepsin G), cysteine (cathepsin S) and metallo- (macrophage metalloelastase, MMP-12) proteases, leading to a protease/antiprotease imbalance. The pathogenesis of COPD arises from an imbalance between the levels of proteases and their endogenous protein inhibitors. Poor regulation of the activity of the released proteases results in the degradation of elastin, the major component of lung connective tissue. Agents capable of suppressing the activity of these enzymes are of potential therapeutic value. Furthermore, the availability of highly selective inhibitors of these enzymes can help delineate the precise role the aforementioned proteases play in COPD. The work described in this thesis is focused on the use of the benzisothiazolin-3-one scaffold in the design of selective inhibitors of PR 3. The synthesized inhibitors are intended to interact with the S' subsites of the enzyme. The results of these studies have demonstrated that highly selective inhibitors of PR 3 over HLE can be realized using this heterocyclic scaffold. / Thesis (M.S.)--Wichita State University, Dept. of Chemistry. / "May 2006." / Includes bibliographic references (leaves 56-61).
33

Design, synthesis, and evaluation of cysteine protease inhibitors

Bridges, Sylvia Shadinger 09 June 2008 (has links)
Proteases are enzymes that cleave protein amide bonds. Proteases are involved in a myriad of biological processes and are considered good targets for drug design. The proteases described herein are cysteine proteases, which utilize a cysteine residue thiol to attack the amide carbonyl, leading to amide bond cleavage. Irreversible inhibitors of cysteine proteases react with the active site cysteine, forming a covalent bond and rendering the enzyme inactive. The first project involved the design and synthesis of aza-peptide epoxide inhibitors for calpain, a clan CA, ubiquitous, calcium-activated human enzyme involved in neurodegeneration. These inhibitors proved to be poor inactivators of calpain, demonstrating that the aza-peptide epoxide is a warhead specific to clan CD cysteine proteases (caspases, gingipains). Subsequently, a known epoxide inhibitor of calpain was optimized to create a more potent inhibitor. Several of these inhibitors were more potent than the parent, and all were demonstrated to inhibit calpain in a breast cancer cell line which was treated with paclitaxel to spike calpain activity. The second project involved the design and solid phase synthesis of aza-peptide Michael acceptor caspases inhibitors. The two goals of this project were to develop a solid phase method for synthesis of inhibitors that are tedious to synthesize in solution phase, and to use a variety of amino acid residues to determine the optimal interactions in the P3? position for various caspases. The synthesis was successful, and the optimal P3? residues were determined. The third project involved the kinetic evaluation of aza-peptide epoxide and Michael acceptor inhibitor designed for the gingipains. Gingipains K and R are virulence factors in the pathology of Porphyromonas gingivalis involved in gingivitis and periodontal disease. These inhibitors proved to be extremely potent inactivators of gingipains, with some of the highest rates of inhibition measured in the Powers laboratory. Gingipain K preferred larger, aromatic moieties in the P1? position, while gingipain R preferred the Michael acceptor inhibitors, with the P1? substituent having less of an impact on potency.
34

High-resolution structures of the proteins human kallikrein 6 and human fibroblast growth factor-1 structure and function relationships /

Bernett, Matthew John. Blaber, Michael. January 2004 (has links)
Thesis (Ph. D.)--Florida State University, 2004. / Advisor: Dr. Michael Blaber, Florida State University, College of Arts and Sciences, Dept. of Chemistry and Biochemistry. Title and description from dissertation home page (viewed June 1, 2005). Document formatted into pages; contains xiii, 110 pages. Includes bibliographical references.
35

Análise da eficácia da polpa do fruto e do extrato das folhas de amoreira (Morus nigra l.) sobre a modulação de marcadores metabólicos e marcadores do estado redox celular em um modelo experimental de diabetes tipo 1.

Araújo, Carolina Morais January 2015 (has links)
Programa de Pós-Graduação em Ciências Biológicas. Núcleo de Pesquisas em Ciências Biológicas, Pró-Reitoria de Pesquisa de Pós Graduação, Universidade Federal de Ouro Preto. / Submitted by giuliana silveira (giulianagphoto@gmail.com) on 2015-12-11T15:36:22Z No. of bitstreams: 1 TESE_AnáliseEficáciaPolpa.pdf: 2506548 bytes, checksum: 2ae77445e1580b08b376827af48f45f7 (MD5) / Approved for entry into archive by Oliveira Flávia (flavia@sisbin.ufop.br) on 2015-12-14T17:29:38Z (GMT) No. of bitstreams: 1 TESE_AnáliseEficáciaPolpa.pdf: 2506548 bytes, checksum: 2ae77445e1580b08b376827af48f45f7 (MD5) / Made available in DSpace on 2015-12-15T12:18:53Z (GMT). No. of bitstreams: 1 TESE_AnáliseEficáciaPolpa.pdf: 2506548 bytes, checksum: 2ae77445e1580b08b376827af48f45f7 (MD5) Previous issue date: 2015 / Diabetes Mellitus (DM) é uma doença metabólica caracterizada por hiperglicemia crônica e alterações no metabolismo de carboidratos, lipídeos e proteinas. Esta desordem leva a uma diminuição na atividade das enzimas antioxidantes, induz danos às células β-pancreáticas e a elevação da atividade de metaloproteinases de matriz tipo 2 (MMP-2) pelo aumento do estresse oxidativo, prejudicando a produção de insulina e, consequentemente, a manutenção da normoglicemia. A Morus nigra L. possui altas concentrações de metabólitos secundários e, principalmente, possui altas concentrações de fenólicos totais e flavonoides. Com base na composição química da Morus nigra, o seu potencial antioxidante pode ser um fator importante para modular o estresse oxidativo induzido pelo diabetes. Neste contexto, nossa meta principal foi avaliar a eficácia da polpa e do extrato das folhas de amoreira na modulação de parâmetros bioquímicos, atividade de MMP e enzimas antioxidantes em um modelo experimental de diabetes tipo 1. Para tal, este estudo foi subdividido em ensaios in vitro e in vivo. In vitro, objetivou-se caracterizar o perfil fitoquímico e antioxidante da polpa e do extrato das folhas de amoreira. In vivo, objetivamos verificar o potencial hipoglicemiante da polpa e extrato das folhas de amoreira bem como a modulação de parâmetros bioquímicos e enzimas relacionadas ao estresse oxidativo em um modelo experimental de diabetes tipo 1. Os resultados da caracterização fitoquímica sugeriram que a polpa de amora apresenta um conteúdo de flavonoides distinto daqueles encontrados no extrato das folhas. Também, observamos que o extrato das folhas apresentou uma maior quantidade de compostos fenólicos e uma maior capacidade de neutralização do radical DPPH quando comparado à polpa de amora. Para a realização dos ensaios in vivo, 32 ratas Fischer, fêmeas, albinas foram distribuídas em quatro grupos experimentais: controle, diabético, diabético tratado com polpa e diabético tratado com extrato das folhas da amoreira. O DM foi induzido por injeção intraperitoneal de aloxano na concentração de 135 mg/kg. Os animais foram tratados durante 30 dias com a polpa ou extrato das folhas de Morus nigra L.. Ao final do tratamento as ratas foram eutanasiadas e as amostras de fígado e de sangue foram coletadas para as análises de parâmetros bioquímicos e metabólicos. Nossos resultados mostraram que o tratamento de ratas diabéticas com o extrato das folhas diminuiu a hiperglicemia induzida pelo diabetes e aumentou as concentrações séricos de insulina. Este efeito não foi observado no tratamento com a polpa de amora. Além disto, o tratamento com a polpa e extrato das folhas de amora foi responsável pela diminuição na atividade de superóxido dismutase (SOD) e um aumento na atividade de catalase (CAT), restabelecendo a razão SOD/CAT aas concentrações do controle. Observamos também que o tratamento com a polpa e o extrato das folhas de amora diminuiu as concentrações de proteina carbonilada em relação ao grupo diabético não tratado. Em relação às metaloproteinases, não encontramos diferenças significativas na atividade de metaloproteinase de matriz tipo 9 (MMP-9), mas houve uma diminuição na expressão e atividade de MMP-2 em ratas diabéticas tratadas com o extrato das folhas de amora. Estes resultados, analisados em conjunto, sugerem que o extrato das folhas da amoreira é mais eficaz no controle glicêmico e na modulação de MMP-2 do que a polpa de amora em modelo experimental de diabetes tipo 1. _____________________________________________________________________________________________ / ABSTRACT: Diabetes mellitus (DM) is a metabolic disease characterized by a chronic disorder of hyperglycemia and alterations in metabolism of carbohydrate, lipid and protein. This disorder decreases antioxidant enzyme activities, damages pancreatic β-cells and induce the elevation of activities's matrix metalloproteinase type 2 (MMP-2) by increases oxidative stress, consequently reducing insulin production and impacting negatively in the maintenance of normoglycemia. Morus nigra L. contains high levels of secondary metabolites, mainly phenolics and flavonoids. Based on the chemical composition of Morus nigra L., its antioxidant potential, may be an important factor for modulating the oxidative stress induced by diabetes. This work was subdivided in assays in vitro and in vivo. The objective in vitro, was characterize the phytochemical and antioxidant profile of pulp and leaves extract of mulberry. The assay in vivo, verified the potential hypoglycemic of leaves extracts and of mulberries's pulp and analyze the modulation of biochemical parameters and enzymes related with the stress oxidative in an experimental model of diabetics type 1. The results of phytochemical characterization suggested that the pulp and the extract of leaves have distinct phenolic compounds, the leaves has more phenolic compounds than the pulp of mulberry. The results also show that the leaves extract has a neutralization capacity bigger than a pulp of mulberry. In the assays in vivo were used 32 Fischer rats.In the experiment 32 rats, female, albino were distributed in four experimental groups: control, diabetic, diabetic treated with pulp and diabetic treated with Morus nigra leaf extract. The DM was induced by introperitoneal injection of aloxano monohidratano (135 mg/kg). The animals were treated during 30 days with Morus nigra pulp or leaf extract. In the end of treatment the rats were euthanized, and the samples of liver and blood were collected for analysis of biochemical and metabolic parameters. The results suggests that treatment of diabetics rats with leaf extract reduced the hyperglycemia induced by diabetes and increased the serum levels of insulin. The treatment with pulp and leaf extract of Morus nigra was responsible for decrease in activity of superoxide dismutase (SOD) and a increase in catalase (CAT) activity, reestablishing the reason SOD/CAT to levels of control animals (animals nondiabetic). We observed that the treatment with Morus nigra pulp and leaf extract decreased the carbonyl protein. In relation to metalloproteinase, there wasn't difference significantly in matrix metalloproteinase type 9 (MPP-9) activity, but there was a decrease in expression and activity of MPP-2 in diabetics rats treated with Morus nigraeaf extract. These results indicate that Morus nigraeaf extract is more efficient in glycemic control and in modulation of MPP-2 than pulp of Morus nigra when applied in an experimental model type 1 diabetes.
36

Estudo das manifestações de varias proteinases do Trypanossoma cruzi

Orsi, Maria Angela 20 November 1995 (has links)
Orientador: Julia Keiko Sakurada / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-20T23:40:43Z (GMT). No. of bitstreams: 1 Orsi_MariaAngela_M.pdf: 4219517 bytes, checksum: 3b74fc60bfe20e7919cb4ebd6130a066 (MD5) Previous issue date: 1995 / Resumo: Os estudos sobre as protease do Trypanosoma cruzi foram realizados utilizando-se as formas epimastigota do parasita. Embora a enzima SH-dependente tenha sido detectada nas diferentes formas evolutivas do parasita (RANGEL et alli,1981 b). No entanto existem poucos estudos das enzimas presentes nas formas tripomastigota e amastigota. Neste trabalho, procuramos investigar através da eletroforese em gel de poliacrilamida, a expressão da proteinase nas formas tripomastigota e amastigota com capacidade de degradara gelatina e obtenção de anticorpos monoclonais reati vos com aproteinase de epimastigota. Os resultados obtidos, no presente trabalho mostram que as formas tripomastigota e amastigota expressam o mesmo pOlipeptideo de 48 kDa com atividade enzimática em pH ácido. Entretanto em pH neutro foi detectada uma banda de 35 kDa, e esse polipeptideo não apresentou nenhuma correlação antigênica com aproteinase de epimastigota.O efeito dos anticorpos monoclonais com especificidade para a proteinase na invasão e multiplicação do T. cruzi nas células hospedeiras mostrou um aumento da infectividade, sugerindo que as proteinase do T.cruzi interferem negativamente na penetração e multiplicação do parasita nas células hospedeiras / Mestrado / Imunologia / Mestre em Ciências Biológicas
37

Ação dos inibidores plasmaticos humanos sobre a atividade da proteinase do Trypanosoma cruzi (Chagas, 1909)

Atta, Ajax Merces 14 July 2018 (has links)
Orientador: Humberto de Araujo Rangel / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-07-14T03:06:24Z (GMT). No. of bitstreams: 1 Atta_AjaxMerces_D.pdf: 4025928 bytes, checksum: 7566d65143049ff5d9262a12d5c07092 (MD5) Previous issue date: 1982 / Resumo: No presente trabalho procuramos obter informações sobre as proteínas responsáveis pela atividade inibitória dos soros humanos normais sobre a atividade proteolltica da proteinase do Trypanosoma Cruzi. Na investigaçio destas proteínas foram realizados testes de inibição da atividade proteinásica com amostras de soros fracionados por eletroforese em gel de agarose e por cromatografia em coluna de Sephadex G-200. Através destes testes foi demonstrado que a atividade inibitória dos soros era mediada por proteínas como mobilidade eletroforética nas regiões das alfa-globulinas,que por sua vez foram eluidas em diferentes volumes da gel-filtração do soro, indicando que possuiam diferentes pesos moleculares. Realizando-se testes imunoquímicos com as frações correspondentes às zonas de inibição obtidas com esta gel-filtração, através do emprego de antissoros monoespecíficos para inibidores plasmáticos de proteinases, foi sugerido que a alfa2-macroglobulina, o inativador de cI, a antitrornbina 111 e a alfal-antitripsina poderiam participar do bloqueio da ação enzimática da proteinase do parasito. A remoção da alfa2-macroglobulina das frações correspondentes à primeira zona de inibição, situada no volume de exclusão da gel-filtração do soro, através da precipitação imune desta proteína com a fração IgG de antissoro de coelho específico para este inibidor, aboliu completamente a atividade inibitória. ...Observação: O resumo, na íntegra, poderá ser visualizado no texto completo da tese digital / Abstract: Not informed. / Doutorado / Imunologia / Doutor em Ciências Biológicas
38

Mast cell recruitment and activation as measures of cyathostomin burden

Clements, Ruth Jocelyn Muriel January 2015 (has links)
Cyathostomins are potentially life threatening parasitic nematodes of adult horses and are highly prevalent worldwide. Infected animals may be asymptomatic or show clinical signs of weight loss, diarrhoea and colic. Third and fourth stage larvae spend a large proportion of their lifecycle encysted in the large intestinal wall where they cannot currently be detected ante mortem. Mast cells are commonly found at interfaces to the external environment, such as the rectum, and these cells and the proteinases they produce have been implicated in protective host immune responses against nematode infection in animals. Previous studies have demonstrated an increase in caecal mast cell proteinase expression during cyathostomin infection. Prior to this study, there were two known equine mast cell proteinases, which had been purified and characterised from a mastocytoma (equine tryptase [eqTRYP] and equine mast cell proteinase-1 [eqMCP-1]). However, as many mammalian species express multiple closely-related chymases it was hypothesised that other equine mast cell proteinases exist that have not yet been characterised and which may be more closely associated with the level of worm burden. The primary objective of this study was to investigate the recruitment of mast cells to the large intestine in cyathostomin infected horses and the expression of mast cell proteinases in response to infection. A further aim was to evaluate the potential of associated mast cell proteinase assays or rectal biopsy mast cell enumeration for utility in diagnostic tests to estimate cyathostomin mucosal burden. A secondary objective was to explore the existence of further mast cell proteinases and the relationship of these enzymes to cyathostomin mucosal burden. Optimised sampling protocols, parasitological, histological and immunohistochemistry techniques were performed to enumerate cyathostomin mucosal burden and to characterise the mast cell populations in the caecum, right ventral colon (RVC) and rectum of naturally infected horses (n=28). Mast cell populations correlated throughout the intestine, providing further evidence of the common mucosal system. EqMCP-1 and eqTRYP labelled mast cells were identified throughout the large intestine. Significant positive linear relationship existed between rectal proteinase-labelled mucosal mast cell populations and both the combined total cyathostomin mucosal burden (CTMB; eqMCP-1, p=0.018; eqTRYP, p=0.048) and the combined total luminal burden (CTLB; eqMCP-1, p=0.009; eqTRYP, p=0.007). Concentrations of eqMCP-1 and eqTRYP in (i) serum, (ii) local serum from venous blood draining the large intestine, and (iii) large intestinal tissue homogenates were assessed using ELISA. There was no significant correlation identified between local and peripheral serum proteinase concentrations suggesting that peripheral serum proteinase levels are not representative of the local proteinase response. There was however a significant negative relationship between peripheral serum eqMCP-1 concentrations and the CTMB, which could relate to the activation and sequestering of proteinases within the gut lumen. Concentrations of eqMCP-1 and eqTRYP measured in local serum did not significantly positively correlate with cyathostomin mucosal burden. There was a significant association observed between intestinal tissue levels of eqMCP-1 and eqTRYP and the CTMB in the RVC (p < 0.023), providing support for their role in the immune response. Four proteinase sequences, equine tryptase (TLP1), Granzyme B-like (GZMBL), putative equine Mast Cell Proteinase-1 (CLP1) and Granzyme(BGH)-like (GZM(BGH)L), were sequenced and the local transcription levels of each of these enzymes assessed using quantitative reverse-transcription PCR. The expression of TLP1 was closely correlated with GZMBL expression, and there was a significant positive relationship observed between TLP1 and GZMBL transcript levels and combined total mucosal burden in the RVC. Both GZM(BGH)L and CLP1 transcript levels were also positively correlated with each other, but the levels of these transcripts were not statistically correlated to any of the cyathostomin parasitological measures assessed here. This work has provided the basis for further rectal biopsy studies to examine the important dynamics of the mast cell response to cyathostomin infection. The results from this thesis, with the demonstration of novel proteinases, are encouraging for further investigation into equine mast cell proteinases and their role in cyathostomin infections.
39

Establishment of a transformation procedure to study the role of trypsin inhibitors in soybean

Mokoena, Tinyiko 12 August 2010 (has links)
The major serine proteinase inhibitors Kunitz and Bowman-Birk-type trypsin are key anti-nutrients responsible for the low nutritional value of raw soy cake, the by product of oil expression from soybean. Traditionally, proteinase inhibitors are eliminated from soy cake through intensive heating, which is highly costly. The long term goal is to generate soybean seeds devoid of trypsin inhibitors through tissue culture and genetic modification of soybean. The RNAi technology has been selected in this study as a technique for down-regulation or silencing these two major serine trypsin inhibitors. Conserved regions, which have been identified by searching NCBI and EMBL database, were targeted for down regulation. Seed specific promoters were also isolated to drive the expression of hairpin constructs designed to down-regulate selected conserved regions of the inhibitors in soybean seeds. RNAi silencing constructs were designed for use in soybean transformation. Ultimately, a tissue culture and transformation protocol for a local soybean variety PAN 512 was established for transformation with two designed RNAi constructs. Suitability of selected promoters was tested by attaching promoters to the gus gene and evaluating specificity of seed expression after soybean transformation using the Agrobacterium tumefaciens strain EHA101. Future work will focus on further optimisation of the transformation protocol and generation of transformed plants carrying the designed silencing vectors. Copyright / Dissertation (MSc)--University of Pretoria, 2010. / Plant Science / unrestricted
40

Molecular biological approaches to the analysis of C1-inhibitor function

Bacon, Louise January 1994 (has links)
No description available.

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