Дисертації з теми "Host-directed"
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Jordan, Brian J. "Directed assembly host-guest chemistry, nanowires, and polymeric templates /." Amherst, Mass. : University of Massachusetts Amherst, 2009. http://scholarworks.umass.edu/dissertations/AAI3359899/.
Повний текст джерелаSüss, Heike Ingrid. "Property directed inclusion formation by channel forming host compounds /." [S.l.] : [s.n.], 2004. http://www.zb.unibe.ch/download/eldiss/04suess_hi.pdf.
Повний текст джерелаPaudyal, Bhesh Raj [Verfasser]. "Small lipid mediators in experimental tuberculosis as target for host-directed therapy / Bhesh Raj Paudyal." Lübeck : Zentrale Hochschulbibliothek Lübeck, 2017. http://d-nb.info/1147619638/34.
Повний текст джерелаPathi, Krishna [Verfasser]. "Establishment of maize resistance to fungal diseases by host-induced gene silencing and site-directed mutagenesis / Krishna Pathi." Hannover : Gottfried Wilhelm Leibniz Universität, 2021. http://d-nb.info/1235138437/34.
Повний текст джерелаLaughery, Zachary. "Synthesis of Molecular Baskets and Introduction of Inward Facing Functionality." ScholarWorks@UNO, 2006. http://scholarworks.uno.edu/td/328.
Повний текст джерелаSmyth, Robin. "Role of Protein Kinase R in the Immune Response to Tuberculosis." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41842.
Повний текст джерелаHlaka, Lerato. "Investigation of minor groove binders (MGB), non-ionic surfactant vesicles (NIV) delivery systems and IL-4i1 as novel pathogen- and host-directed drug therapy for tuberculosis." Doctoral thesis, Faculty of Health Sciences, 2019. http://hdl.handle.net/11427/31054.
Повний текст джерелаMarzo, Escartín Elena. "Tuberculosi pulmonar: com evitar el pas de granuloma a cavitat. Estudi de la inflamació en la patogènesi de la malaltia tuberculosa i desenvolupament de noves estratègies terapèutiques." Doctoral thesis, Universitat Autònoma de Barcelona, 2014. http://hdl.handle.net/10803/285649.
Повний текст джерелаLa tuberculosis (TB) es una epidemia global causada por Mycobacterium tuberculosis (Mtb) con 8,6 millones de enfermos y 1,3 millones de muertes cada año. El tratamiento actual con antibióticos es muy largo, caro i presenta efectos adversos. Cuando una persona se infecta con Mtb puede controlar la infección en el 90% de los casos (infección latente), desarrollando solamente lesiones microscópicas en el pulmón: granulomas de 0,5mm de diámetro invisibles en una radiografía. En el 10% restante la infección no se controla y se desarrollan lesiones mayores, típicamente cavidades de unos 20mm en adultos inmunocompetentes. La clave para comprender la patogénesis de la TB activa es el paso de granulomas de 0,5mm a cavidades de gran tamaño. En esta tesis se ha desarrollado un modelo murino mediante la infección endovenosa de ratones C3HeB/FeJ con la cepa virulenta H37Rv de Mtb, que desarrolla lesiones con necrosis granulomatosa central y licuefacción, muy similares a las lesiones previas a la cavitación en humanos. Las lesiones crecen de forma exponencial debido en parte a la infiltración neutrofílica masiva, y en parte a la coalescencia de las lesiones vecinas. Los estudios comparativos con la cepa resistente C3H/HeN y el uso de antiinflamatorios no esteroideos (AINEs) en el modelo han confirmado que la inflamación es un factor clave en el desarrollo de la TB activa, y también que los AINE podrían utilizarse como tratamiento coadyuvante en la TB pulmonar en adultos inmunocompetentes, dado que en frenar la inflamación ayudan a controlar la enfermedad. Por otro lado se ha desarrollado un método profiláctico que mediante la administración oral de dosis bajas de micobacterias inactivadas induce tolerancia al Mtb, y en consecuencia una respuesta inmunitaria más equilibrada, conteniendo la respuesta Th17, resultando en una mejora de la supervivencia, la carga bacilar y la histopatología de los ratones. Conclusiones: Se ha desarrollado un modelo murino de TB activa, se ha caracterizado el papel de la inflamación en el desarrollo de cavidades, concretamente de la infiltración masiva de neutrófilos, se ha propuesto el uso de AINEs como tratamiento coadyuvante para la tuberculosis activa en adultos inmunocompetentes, y se ha desarrollado un nuevo método profiláctico que podría evitar la enfermedad mediante la inducción de tolerancia oral al Mtb que se consigue con la administración oral de bajas dosis de micobacterias inactivadas.
Tuberculosis (TB) is a global epidemic caused by Mycobacterium tuberculosis (Mtb). In 2012 an estimated 8,6 million of people developed TB and 1,3 million died from the disease. The current treatment with antibiotics is expensive, long-lasting and presents adverse effects. When people are infected with Mtb the infection is controlled in the 90% of the cases, developing microscopic lesions in the lungs, 0,5mm of size granulomas, invisibles to the X-rays. In the other 10% the infection is not controlled and bigger lesions are developed: in immunocompetent adults the most characteristic lesion is a cavity sized about 20mm of diameter. The clue to understand active TB pathogenesis must be the development of 20mm cavities from 0,5mm granulomas. In this work a murine model has been developed through the endovenous infection of C3HeB/FeJ mice with H37Rv virulent strain of Mtb, which develops lesions presenting central granulomatous necrosis and further liquefaction, very similarly to the lesions previous to cavity formation in human patients. The lesions grow exponentially due to massive neutrophilic infiltration and coalescence of neighbour lesions. The comparative studies with the resistant mice strain C3H/HeN and the use of non-steroidal anti-iflammatory drugs (NSAIDs) in the model confirmed that inflammation is clue in the active TB development, and also that NSAIDs could be use as adjunctive therapy in the treatment of pulmonary TB in immunocompetent adults, through control of excessive inflammation. On the other hand, a prophylactic method has been developed consisting on induction of tolerance to Mtb through oral administration of low doses of heat-killed mycobacteria, driving to a more balanced immune response, limiting Th17 development and resulting in a better outcome of mice in terms of survival, histopathology and bacillary load in lungs. Conclusions: A murine active TB model has been developed, and the role of inflammation in cavity formation characterized, namely the role of massive neutrophilic infiltration. The use of NSAIDs has been proposed as an adjuvant treatment of active TB in immunocompetent adults, and a new prophylactic method has been developed that could avoid the disease by induction of oral tolerance to Mtb through the administration of heat killed micobacteria at low doses.
Matsui, Yusuke. "Defining HIV-1 Vif residues that interact with CBFβ by site-directed mutagenesis". Kyoto University, 2015. http://hdl.handle.net/2433/199190.
Повний текст джерелаChiu, Chia-I., and 邱嘉儀. "Evaluation of Host-Directed Anti-Bacterial Agents Against Intracellular Salmonella Typhimurium." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/w39y38.
Повний текст джерела國立臺灣大學
醫學檢驗暨生物技術學研究所
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Some bacteria pathogens that can reside in host cells, for example: Salmonella spp. and will lead to chronic infection. These pathogens will invade host cells to evade external antibiotics’ attack and continue to survive in the cell, thus they are difficult to completely eradicated with antibiotics and often lead to drug resistance. Host-directed therapies have been proposed in many studies for the treatment of intracellular bacterial infections. AR-12 (a.k.a. OSU-03012), was originally used as an anti-cancer drug and have been showed in our previous studies that AR-12 combined with aminoglycoside antibiotics can significantly clear intracellular bacteria, making AR-12 as a potential drug for the treatment of intracellular bacterial infections. As the half-lethal dose (IC50) of AR-12 is close to half-effective concentration, we decided to conduct AR-12 structure optimization. In addition, we previously found that an antipsychotic drug - loxapine in combined with aminoglycoside antibiotics showed antimicrobial efficacy and significantly cleared intracellular bacteria with a high half-lethal dose (IC50), however, loxapine cannot prolong the survival of mice. Therefore, we hope to obtain potential drugs by synthesis of loxapine derivatives. In this study, we obtained 167 AR-12 derivatives and 5 loxapine derivatives. We tested the anti-bacterial activity against intracellular Salmonella Typhimurium of all compounds and simultaneously tested toxicity towards host cells to identify more effective and low toxicity drugs. At the same time, we used loxapine as the representative to explore its antibacterial mechanism. First, we performed AR-12 derivative screening. We found that seven compounds have lower toxicity and equal antibacterial activity to AR-12. Another seven compounds showed better antibacterial activity but equal toxicity to AR-12. We further evaluated the efficacy of these 14 compounds in combination with aminoglycoside antibiotics for the treatment of intracellular S. Typhimurium. The results of the cell infection experiments showed that 4 of 14 compounds had no significant antibacterial activity. Subsequent test of the three compounds with highest selectivity for antibacterial activity against multidrug-resistant strains also demonstrated the same effect. In the cell infection test and toxicity test of loxapine, three compounds showed better antibacterial ability than loxapine, but with high toxicity, thus there was no high selectivity. At present, the synthesis and test of AR-12 derivatives and loxapine derivatives are ongoing. The above findings demonstrated that the antibacterial activity of AR-12 can be dissociated from its antiproliferative activity via structure optimization and that hit compounds are potential to be served as antibiotic adjuvants for MDR Salmonella Typhimurium infection.
Truong, David Minh. "Mobile group II intron : host factors, directed evolution, and gene targeting in human cells." Thesis, 2014. http://hdl.handle.net/2152/30349.
Повний текст джерелаtext
Huang, Hong Ming. "Complex roles ankyrin-1 plays in malaria infections." Phd thesis, 2016. http://hdl.handle.net/1885/117238.
Повний текст джерелаSmith, CM. "An Investigation of novel host-directed antimalarial therapeutics through genetic and pharmacological targeting of haem biosynthetic enzymes." Thesis, 2012. https://eprints.utas.edu.au/22700/1/Clare_Smith_whole_thesis_2012.pdf.
Повний текст джерелаVeloso, Paulo Rúben Fernandes. "Enzyme engineering for improved xylanase applicability and characterization of a xylan metabolizing Saccharomyces cerevisiae." Master's thesis, 2017. http://hdl.handle.net/1822/45831.
Повний текст джерелаA xylanase (pXyl) isolated from the Antarctic bacterium Pseudoalteromonas haloplanktis is being commercialized worldwide for use in the baking industry. pXyl is a highly active coldadapted enzyme belonging to glycoside hydrolase family 8. It maintains high activity at low temperatures, is resistant to xylanase inhibitors and is highly specific for long chain unsubstituted xylan. However, a low stability and activity at acidic pHs, due mainly to precipitation, prevents the use of this enzyme in other industrial activities. In this study, the protein engineering techniques of random mutagenesis and site directed mutagenesis were investigated in an attempt to overcome the instability and loss of activity of pXyl at acidic pHs. Initially, random mutagenesis was investigated as this offers a powerful tool for identification of novel positive mutations in the absence of any knowledge of the protein involved. A critical limitation with this approach is the availability of a high throughput screening method for facile identification of positive mutants. We investigated an in-house strain of Saccharomyces cerevisiae for use in genetic complementation screening. This host has been engineered to enable growth on xylose and here it was attempted to develop this for growth on xylan by inclusion of both a β-xylosidase gene and the gene for pXyl. Unfortunately, following multiple attempts we were unable to isolate a strain capable of growth with xylan as the sole carbon source. We next turned our attention to site-directed mutagenesis. It is proposed that the strong precipitation of pXyl at low pHs may be related to its highly hydrophobic surface, as well as to negative surface amino acids which become protonated and more hydrophobic and hence more prone to precipitation at these lower pHs. Therefore, the highly exposed negative residues which do not participate in stabilising interactions in pXyl were identified (D70, E94, E95, E342 and E377) and mutated to the highly polar residue serine in an attempt to reduce acidic pH precipitation. Only E94S and E342S were successfully produced, purified and characterised. Both mutants showed minor increases in solubility at both acidic and basic pHs as compared to the wild-type enzyme, as well as an improvement in thermal stability, albeit being accompanied by alterations in the conformation. This preliminary study indicates the potential of the approach used in overcoming pXyl precipitation at acidic pHs.
A enzima xilanase (pXyl) isolada da bactéria antártica Pseudoalteromonas haloplanktis está mundialmente a ser comercializada como aplicação na indústria de panificação. A pXyl é uma enzima extremamente ativa e adaptada a baixas temperaturas, pertencendo à glycoside hydrolase family 8. Esta mantém uma elevada atividade a baixas temperaturas, é resistente a inibidores de xilanases e é específica para xilanos de cadeia longa não substituídos. No entanto, a baixa estabilidade e atividade a pHs ácidos, devido principalmente à sua precipitação nesta condição, impede a utilização desta enzima noutras áreas industriais. Neste estudo, as técnicas de engenharia de proteínas, mutagénese aleatória e mutagénese dirigida, foram utilizadas com o objetivo de superar a instabilidade e a perda de atividade da pXyl a pHs ácidos. Inicialmente, foi investigada a mutagénese aleatória, uma vez que esta técnica oferece uma estratégia poderosa para a identificação de novas mutações positivas nos casos em que a proteína envolvida não é totalmente conhecida. Uma limitação preponderante no uso desta abordagem é a disponibilidade de um método de rastreio de alto rendimento para a fácil identificação de mutantes positivos. Por isso, uma estirpe de Saccharomyces cerevisiae construída no nosso laboratório foi investigada para o seu uso no rastreio de complementações genéticas. Neste trabalho, este hospedeiro, previamente geneticamente manipulado para crescer em xilose, foi também adaptado para poder crescer em xilano. Para isso, os genes que codificam para uma β - xilosidase e para a pXyl foram expressos nesta estirpe. Infelizmente, após várias tentativas, não foi possível isolar uma estirpe capaz de crescer em xilano como única fonte de carbono. A segunda parte do trabalho focou-se na mutagénese dirigida. Estudos relacionados propõe que a forte precipitação da pXyl a pH baixos pode estar relacionada com a sua superfície altamente hidrofóbica, assim como com os aminoácidos negativos superficiais que se tornam protonados e mais hidrofóbicos e, portanto, mais propensos à precipitação nestes pHs. Por conseguinte, os resíduos negativos mais expostos ao solvente que não participam em interações de estabilização na pXyl foram identificados (D70, E94, E95, E342 e E377) e mutados por serina, um resíduo fortemente polar, numa tentativa de reduzir a precipitação a pH ácido. Apenas os mutantes E94S e E342S foram produzidos, purificados e caraterizados com sucesso.Ambos os mutantes apresentaram um ligeiro aumento na solubilidade tanto a pHs ácidos como básicos em comparação com a enzima selvagem assim como um aumento na estabilidade térmica, embora acompanhados por alterações na conformação. Este estudo preliminar indica o potencial da abordagem utilizada na diminuição da precipitação da pXyl a pHs ácidos.
Shee, Somnath. "Manipulating Bacterial and Host Reactive Oxygen Species (ROS)- based mechanisms to potentiate killing of Mycobacterium tuberculosis (Mtb)." Thesis, 2021. https://etd.iisc.ac.in/handle/2005/5680.
Повний текст джерелаWelcome-DBT