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1
Moore, Sandra. "Dynamics of cholera epidemics in Haiti and Africa." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5505/document.
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Le cholera est une maladie diarrhéique aiguë due à la consommation d’eau ou d’aliments contaminés par des souches toxigéniques de Vibrio cholerae. Selon le “paradigme du choléra”, la maladie est provoquée par une exposition à un réservoir environnemental de V. cholerae avec des épidémies directement modulées par des facteurs environnementaux. Cependant, comme divers arguments plaident contre ce dogme, nous avons voulu élucider les mécanismes de la dynamique des épidémies de cholera dans trois foyers situés en Haïti, en République Démocratique du Congo (RDC) et en Afrique de l’Ouest. Nous avons associé une analyse temporo-spatiale des épidémies à une étude génétique des isolats de V. cholerae. En Haïti, nous avons cherché à savoir si les épidémies actuelles étaient dues à des souches toxigéniques de V. cholerae O1 durablement implantées dans l’environnement aquatique. En Afrique de l’Ouest, notre étude a révélé qu’Accra, la capitale du Ghana, était le principal foyer de choléra pour l’ensemble des pays d’Afrique de l’Ouest situés à l’Ouest du Nigeria. Le réseau d’eau d’Accra a probablement joué un rôle dans la propagation rapide de V. cholerae vers la majorité des quartiers de la ville. Les épidémies de choléra ont diffusé vers les autres pays sous la forme de vagues épidémiques et plusieurs épidémies ont été liées à la migration de populations à risque comme certains pêcheurs. En conclusion, notre réflexion globale sur les épidémies de choléra dans ces trois foyers distincts nous donne une vision cohérente des mécanismes d’émergence et de diffusion du choléraCholera is an acute diarrheal disease caused by consumption of water or food contaminated with toxigenic Vibrio cholerae. According to the "cholera paradigm", the disease is contracted by exposure to environmental reservoirs of V. cholerae, with outbreaks driven directly by climatic factors. However, as recent findings argue against this dogma, we aimed to elucidate the dynamics of cholera outbreaks in three global foci: Haiti, Democratic Republic of the Congo (DRC) and West Africa. We combined spatiotemporal analysis of epidemics with genetic assessment of V. cholerae isolates. In Haiti, we assessed whether outbreak re-emergence during the rainy season was due to toxigenic V. cholerae O1 strains that have settled into the aquatic environment. Instead, we found that the re-emergence of outbreaks was likely due to persisting outbreaks during the dry season that were insufficiently controlled, rather than an environmental reservoir of V. cholerae O1. In West Africa, our study revealed that Accra, Ghana was the hotspot of cholera in the entire region of West Africa, west of Nigeria. The Accra water network likely played a role in rapid diffusion of V. cholerae throughout the city. Cholera outbreaks spread from Accra into other countries in a wave-like fashion. Distinct outbreaks were linked via migration of at-risk populations, such as certain fishermen. In conclusion, our global reflection of cholera epidemics in these three distinct foci provides a coherent vision of the mechanisms of cholera emergence and diffusion
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Nygren, Erik. "A mouse model for direct evaluation of cholera vaccines /." Göteborg : Dept. of Microbiology and immunology, Institute of Biomedicine, The Sahlgrenska Academy at University of Gothenburg, 2009. http://hdl.handle.net/2077/19376.
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Le, Roux Wouter Jacobus. "Population dynamics of Vibrio cholerae in the Vaal Barrage." Pretoria : [s.n.], 2005. http://upetd.up.ac.za/thesis/available/etd-02162007-175110.
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Occhino, Deborah Ann. "Vibrio cholerae iron transport : characterization of two tonB systems and components of a heme transport system /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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Falklind, Jerkérus Susanna. "Vibrio cholerae O139 : identification, characterization and vaccine strategies /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-696-0/.
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Mitchell, Daniel David. "Cholera toxin inhibition and EpsF from its secretion system /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/9210.
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Zo, Young-Gun. "Phylogenomic and structural analyses of Vibrio cholerae populations and endemic cholera." College Park, Md. : University of Maryland, 2005. http://hdl.handle.net/1903/3090.
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Thesis (Ph. D.) -- University of Maryland, College Park, 2005.Thesis research directed by: Marine-Estuarine-Environmental Sciences. Title from t.p. of PDF. Includes bibliographical references. Published by UMI Dissertation Services, Ann Arbor, Mich. Also available in paper.
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Bougoudogo, Fiabou. "Contribution à l'étude de l'immunité protectrice contre le choléra : rôle des anticorps vibriocides reconnaissant le polysaccharide spécifique du lipopolysaccharide de "Vibrio cholerae" O:1." Paris 11, 1994. http://www.theses.fr/1994PA114831.
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Lee, Jason J. "Neutrophil responses to Vibrio cholerae autoinducer-1 and structural analogues." Thesis, Griffith University, 2021. http://hdl.handle.net/10072/404172.
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Vibrio cholerae is a pathogen responsible for cholera, an infectious disease that usually manifests as severe diarrhea. V. cholerae cells can regulate population-wide gene expression changes in a density-dependent manner, in a process known as quorum sensing (QS). QS involves communication between bacterial cells using secreted signalling molecules. V. cholerae autoinducer-1 (CAI-1) is the dominant signalling molecule in the V. cholerae QS circuit and has roles in regulating biofilm formation/degradation and expression of virulence genes.
Interactions between bacterial-produced QS molecules and eukaryotic cells have been documented. This is known as interkingdom or cross-kingdom signalling. CAI-1 has been reported to act as a chemoattractant for the nematode, Caenorhabditis elegans which feeds on V. cholerae cells as a food source. Legionella autoinducer-1 (LAI-1), which is structurally similar to CAI-1, is a signalling molecule produced by Legionella pneumophila. LAI-1 has been reported to impede the migration of Dictyostelium discoideum amoebae and macrophage-like RAW 264.7 cells, and has also been shown to destabilise the cytoskeleton of RAW 264.7 cells. Structural analogues of CAI-1 with more potent activity within the V. cholerae QS circuit have been developed as potential novel therapeutics against cholera. These QS agonists would force the bacterial cells to express high cell density behaviours, impairing colonisation and promoting detachment, therefore reducing pathogenesis.
These previous findings led to the hypothesis that CAI-1 and structural analogues may have immunomodulatory effects on host cells during V. cholerae infection, particularly recruited immune cells which may be exposed to CAI-1 during cholera. There are several lines of evidence the neutrophil recruitment is prominent during cholera and that these granular leukocytes play a role in controlling infection.
Thus, the key aims of this study were to characterise interactions between CAI-1, as well as structural analogues of CAI-1, and neutrophils. In vitro HL-60 cell culture revealed an upregulation of CD11b expression when cells were differentiated with DMSO in the presence of CAI-1. This increased differentiation marker expression was at the expense of both cell viability and total cell count. Additionally, two 3-acyl pyrrole analogues of CAI-1 also increased CD11b expression greater than CAI-1, when cells were differentiated with DMSO in the presence of either analogue. Again, this resulted in significantly reduced cell viability and total cell count, although at similar levels to CAI-1. HL-60 cells differentiated in the presence of CAI-1 or either analogue were generally more granular than cells differentiated with DMSO alone.
The effects of CAI-1 and structural analogues on neutrophil effector functions were assessed, namely chemotaxis and oxidative burst. CAI-1 did not act as a chemoattractant for DMSO-differentiated HL-60 cells, nor did it reduce or enhance migration towards fMLP, a known chemoattractant. Pre-treatment of differentiated HL-60 cells with CAI-1 or one of the 3-acyl pyrrole analogues for 3 h resulted in decreased reactive oxygen species production. However, concomitant reduction in cell viability was observed over 3 h.
Preliminary experiments assessed the effect of CAI-1 on primary human neutrophils. Isolated neutrophils appeared larger and less round with CAI-1 treatment. In contrast, CAI-1 treatment of whole blood resulted in apparent reductions in cell size as assessed by flow cytometry. Expression of activation markers (CD11b, CD64, CD66b) on granulocytes in whole blood appeared unaffected by CAI-1.
Overall, the results within this study shed light onto the cross-kingdom interactions that may exist between host cells and bacterial signalling molecules. Identifying these interactions may lead to a deeper understanding of additional mechanisms that may be involved in V. cholerae pathogenesis. Additionally, these interactions may be important in revealing off-target effects that developing novel therapies, which interfere with bacterial QS, may have on host cells.
These data highlight an advance that reveals many opportunities for further investigations surrounding host-microbe interactions.Thesis (Masters)
Master of Medical Research (MMedRes)
School of Medical Science
Griffith Health
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Salmon, François. "Le choléra au Pérou : leçon pour un continent à risque." Paris 5, 1994. http://www.theses.fr/1994PA05P013.
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Henze, Charlotte E. "Cholera in Saratov, 1892-1910." Thesis, University of Cambridge, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436743.
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Fonseca, Ana Glória Rodrigues Sanches da. "Seroprevalência de cólera em área endémica : estudo." Master's thesis, Faculdade de Ciências Médicas. Universidade Nova de Lisboa, 2007. http://hdl.handle.net/10362/4842.
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Ao longo da história, a cólera tem assolado populações sob a forma de epidemias e pandemias com elevada morbimortalidade, que condicionam o desenvolvimento das regiões atingidas (120.000 óbitos estimados por ano a nível mundial). Em 2001, 94% (173.359 casos) dos casos de cólera foram notificados no continente africano (OMS). A cidade da Beira é considerada área de endemo-epidemicidade de cólera.
Na cidade da Beira foi realizado um estudo de seroprevalência de cólera (serogrupo O1), em período inter-epidémico, através do doseamento de anticorpos vibriocida, numa amostra de conveniência de 136 indivíduos adultos sem história de vacinação prévia contra a cólera. Obteve-se uma seroprevalência de 2,2%, que não pode ser extrapolada para a população em geral. Ambas as estirpes do serogrupo O1 (Inaba e Ogawa) foram identificadas.
A metodologia utilizada é exequível em regiões com suporte laboratorial básico e pode ter interesse como ferramenta de vigilância epidemiológica da cólera na cidade da Beira, dado que a seroprevalência em anticorpos vibriocida traduz a imunidade de grupo da população. A monitorização da seroprevalência pode contribuir para orientar as estratégias de intervenção no sentido do controlo da cólera, nomeadamente na implementação de uma campanha de vacinação.
De facto, tendo em conta o impacto da cólera na população e as limitações da estratégia existente, urge equacionar de forma objectiva o papel da vacinação oral na estratégia de controlo da cólera na cidade da Beira.
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Selamolela, S. D. "A retrospective study on the geographical distribution of cholera in Limpopo Province, South Africa." Thesis, University of Limpopo, 2016. http://hdl.handle.net/10386/2420.
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Thesis (MPH.) -- University of Limpopo, 2016Introduction: During mid-November 2008, eleven acute watery diarrhoea cases with the suspicion of cholera like symptoms were detected by a diarrhoea surveillance system at Musina Hospital in Vhembe district - Limpopo Province, South Africa. These cases included eight Zimbabwean and three South African citizens. Laboratory test performed on stool specimens confirmed Vibrio cholerae serogroup 01 Ogawa as the causative pathogen for these reported acute watery diarrhoea cases. Within eight weeks of its onset, the outbreak spread to all the five districts of Limpopo. So far between 15 November 2008 and 01 June 2009, the cumulative number of cases of acute watery diarrhoea reported from five districts of Limpopo Province stands at 4634 including 30 confirmed cholera deaths with an overall case fatality rate of 0.65%. Of these reported cases, Vibrio cholerae has been laboratory confirmed in 656 samples. Methodology: A database was received from the Limpopo Department of Health having all reported cholera cases during the 2008 and 2009 outbreak in Limpopo Province. The data was analysed using STATA statistical software version 12 for windows (STATA Corporation, College Station, Texas). Results: The cholera affected all ages, but the geographic distribution of the disease was very heterogeneous in Limpopo Province. The highest and lowest numbers of cases were reported in Capricorn and Mopani districts, respectively. The majority of the cases 55% (N=2 542) were females. Children less than five years of age 14.2% (N=652) were less affected by the disease. About 73.8% of the cases were aged between O and 44 years. The first four weeks of cholera outbreak strictly included a day-to-day admixture of Zimbabweans and South Africans presenting in the health facilities. The outbreak then affected most South Africans after week five of the epidemic. Conclusion: The cholera outbreak has affected all the five districts of Limpopo Province in South Africa, and new cases continued to be reported until first week of June 2009. There was a link between the Zimbabwean and South African cholera outbreak in Limpopo province.
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Mann, Maretta Clare, and n/a. "Sialylmimetics as Potential Inhibitors fo Vibrio Cholerae Sialidase." Griffith University. Institute for Glycomics, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20061006.083947.
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Cholera is an epidemic infectious diarrhoeal disease that for centuries has proven its frightening ability to cause rapid and widespread loss of human life. All symptoms associated with cholera are a result of rapid dehydration due to infection by pathogenic strains of the bacterium Vibrio cholerae. The damaging effects associated with cholera are mainly attributed to the toxin, which is secreted by the bacterium and infects cells lining the gastrointestinal tract. A sialidase, also secreted by the bacterium, is believed to facilitate toxin uptake by the gastrointestinal epithelium. V. cholerae sialidase is therefore a potential target for therapeutic intervention. A survey of the literature reveals that sialidases from different species share common features with respect to their structure, substrate specificity and catalytic mechanism. The unsaturated sialic acid, Neu5Ac2en, inhibits most exosialidases with a dissociation constant of inhibitor of -10-4 to-10-6 M and has frequently been used as a template in the design of more potent sialidase inhibitors. In the case of V. cholerae sialidase, there have been no inhibitors reported to date that are significantly more potent than Neu5Ac2en itself The present research aimed to develop a range of mimics of Neu5Ac2en, which contain various substituents to replace the C-6 glycerol side chain, as potential inhibitors of V cholerae sialidase. The x-ray crystal structure of V cholerae sialidase was used to explore potential interactions between active site residues and C-6 modified Neu5Ac2en mimetics of known inhibitory potency. Opportunities for interactions within the glycerol side chain pocket in the active site of V cholerae sialidase are discussed. A novel synthetic strategy was developed for the synthesis of a series of glucuronidebased Neu5Ac2en mimetics starting from readily available GIcNAc. This approach was employed for the preparation of Neu5Ac2en mimetics that contained an ether or thioether substituent as replacement of the glycerol side chain of Neu5Ac2en. Progress was also made towards the synthesis of a series of C-6 acylamino Neu5Ac2en mimetics. Analysis by 1H NMR spectroscopy showed that the acylamino derivatives adopted a half-chair conformation that was similar to the conformation of Neu5Ac2en but different to the conformation adopted by the ether and thioether derivatives prepared. The inhibitory activity of the C-6 ether and thioether Neu5Ac2en mimetics prepared was evaluated in vitro using an enzyme assay. It was found that most of the derivatives inhibited V. cholerae sialidase with a K1 of approximately 1O-4 M. The derivatives containing a hydrophobic side chain were found to be slightly more potent compared to derivatives with more hydrophilic side chains. A more detailed study of binding interactions between the C-6 thioether Neu5Ac2en mimetics and V cholerae sialdiase was carried out using STD 1H NMR spectroscopy and computational molecular modelling.
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Mann, Maretta Clare. "Sialylmimetics as Potential Inhibitors fo Vibrio Cholerae Sialidase." Thesis, Griffith University, 2004. http://hdl.handle.net/10072/367187.
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Cholera is an epidemic infectious diarrhoeal disease that for centuries has proven its frightening ability to cause rapid and widespread loss of human life. All symptoms associated with cholera are a result of rapid dehydration due to infection by pathogenic strains of the bacterium Vibrio cholerae. The damaging effects associated with cholera are mainly attributed to the toxin, which is secreted by the bacterium and infects cells lining the gastrointestinal tract. A sialidase, also secreted by the bacterium, is believed to facilitate toxin uptake by the gastrointestinal epithelium. V. cholerae sialidase is therefore a potential target for therapeutic intervention. A survey of the literature reveals that sialidases from different species share common features with respect to their structure, substrate specificity and catalytic mechanism. The unsaturated sialic acid, Neu5Ac2en, inhibits most exosialidases with a dissociation constant of inhibitor of -10-4 to-10-6 M and has frequently been used as a template in the design of more potent sialidase inhibitors. In the case of V. cholerae sialidase, there have been no inhibitors reported to date that are significantly more potent than Neu5Ac2en itself The present research aimed to develop a range of mimics of Neu5Ac2en, which contain various substituents to replace the C-6 glycerol side chain, as potential inhibitors of V cholerae sialidase. The x-ray crystal structure of V cholerae sialidase was used to explore potential interactions between active site residues and C-6 modified Neu5Ac2en mimetics of known inhibitory potency. Opportunities for interactions within the glycerol side chain pocket in the active site of V cholerae sialidase are discussed. A novel synthetic strategy was developed for the synthesis of a series of glucuronidebased Neu5Ac2en mimetics starting from readily available GIcNAc. This approach was employed for the preparation of Neu5Ac2en mimetics that contained an ether or thioether substituent as replacement of the glycerol side chain of Neu5Ac2en. Progress was also made towards the synthesis of a series of C-6 acylamino Neu5Ac2en mimetics. Analysis by 1H NMR spectroscopy showed that the acylamino derivatives adopted a half-chair conformation that was similar to the conformation of Neu5Ac2en but different to the conformation adopted by the ether and thioether derivatives prepared. The inhibitory activity of the C-6 ether and thioether Neu5Ac2en mimetics prepared was evaluated in vitro using an enzyme assay. It was found that most of the derivatives inhibited V. cholerae sialidase with a K1 of approximately 1O-4 M. The derivatives containing a hydrophobic side chain were found to be slightly more potent compared to derivatives with more hydrophilic side chains. A more detailed study of binding interactions between the C-6 thioether Neu5Ac2en mimetics and V cholerae sialdiase was carried out using STD 1H NMR spectroscopy and computational molecular modelling.Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Biomolecular and Physical Sciences
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Kazaji, Dieudonne KA'ngweji. "Factors contributing to the prevalence of cholera during 2008 to 2009 in Vhembe District of Limpopo Province, South Africa." Thesis, University of Limpopo, 2015. http://hdl.handle.net/10386/1616.
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Thesis (MPH.) -- University of Limpopo, 2015Cholera is an acute enteric infection caused by the ingestion of bacterium Vibrio cholerae present in faecally contaminated water or food. Primarily linked to insufficient access to safe water and proper sanitation, its impact can be even more dramatic in areas where basic environmental infrastructures are disrupted or have been destroyed. The aim of the study was to investigate the factors contributing to the prevalence of cholera and the environmental risk factors associated with cholera in the Vhembe district of Limpopo province between 2008 and 2012. The objectives of the study were to identify environmental risk factors for cholera and to determine the number of cholera cases in the Vhembe district. The study used a quantitative, retrospective and cross-sectional research method. The records of 317 patients who met the study criteria were reviewed using an audit tool. The Statistical Package for Social Sciences (SPSS) version 22 was used to analyze the data. The results revealed that lack of adequate hygiene practices, limited access to safe drinking water, lack of safe food preparation and handling, and inadequate sanitation system are risk factors associated with cholera. The study recommends prevention, control of cholera outbreak and case management. Keywords: Cholera, outbreak, Vibrio cholerae 01 and 0139, Watery diarrhea (ricewater), Prevalence, Risk factors.
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Sendzik, Walter. "The 1832 Montreal cholera epidemic : a study in state formation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ37236.pdf.
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Yáñez, Marissa Elena. "Structural and functional studies of minor pseudopilins from the type 2 secretion system of Vibrio cholerae /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/8086.
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Edwin, Aaron. "Structural and functional studies of the secreted metalloprotease PrtV from Vibrio cholerae." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-84553.
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Cholera, an acute diarrheal diseases caused by the intestinal infection of the pathogenic bacterium Vibrio cholerae, continues to be a global killer in the world today. PrtV, a secreted zinc metalloprotease, is a potent cytotoxic virulence factor of V. cholerae. The 102 kDa full length multi-domain PrtV protein undergoes several N and C terminal modifications before being secreted as a 81 kDa pro-protein. The activation of the pro-protein is calcium dependent. The removal of calcium triggers auto-proteolysis to give a stable active protease with the catalytic zinc binding domain. The aim of the thesis was to study the structure and function of the PrtV protein. The results from paper I, identified the end product of the maturation of PrtV as the stable 37 kDa M6 active domain, and not a 55 kDa complex as reported earlier. Results also showed the this 37 kDa active M6 domain alone was sufficient for catalytic activity. A revised model for the maturation of PrtV was proposed. Individual domains were isolated from the PrtV protein by domain phasing methods. This included the N-terminal domain (residues 23-103), the PKD1 domain (residues 755-839), and a 25 kDa fragment (residues 589-839). The isolated domains were recombinantly over expressed as fusion proteins to increase expression and solubility. The PKD1 domain was purified to homogeneity and crystallized. The structure of the PKD1 domain reported in paper II, was solved by X-ray crystallography at an atomic resolution of 1.1 Å. From the structure, a previously unknown calcium binding site was identified at the N-terminal of the PKD1 domain. The structure also revealed two conformations for the PKD1 domain depending on free or bound calcium. From the structure, a function of the PKD1 domain as a protector of the cleavage site in the linker region between the M6 domain and the PKD1 domain in the presence of calcium was elucidated. A new model for the activation of PrtV was given. In paper III, the structure of the N-terminal domain solved by NMR spectroscopy was reported. The structure revealed two well defined helices but a third predicted helix was found to be unstructured.
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Hopkins, Brett A. "Fowl cholera in turkeys : vaccination, pathogenicity, and DNA analysis /." free to MU campus, to others for purchase, 1999. http://wwwlib.umi.com/cr/mo/fullcit?p9962544.
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Wehinger, Krafft Richard. "Cholera in Yemen post COVID-19 : A Case Study on the Challenges Humanitarian organizations Face in Ending Cholera." Thesis, Uppsala universitet, Statsvetenskapliga institutionen, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-432710.
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Rebaudet, Stanislas. "Etude dynamique des épidémies de choléra en Afrique et en Haïti et application à la mise en place de stratégies d'élimination." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5055/document.
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Le choléra est une diarrhée hydrique sévère volontiers épidémique causée par des Vibrio cholerae O1 toxinogènes. Ses déterminants environnementaux ont donné naissance à un paradigme influent sur les stratégies de lutte, qui sont se sont avérées peu efficientes en Afrique comme en Haïti. Elles pourraient être améliorées par une meilleure compréhension de la dynamique des épidémies. La synthèse bibliographique des influences de l'environnement sur les épidémies de choléra en Afrique y montre les limites du paradigme environnemental. L'étude multidisciplinaire des origines de l'épidémie de choléra en Guinée en 2012 suggère fortement qu'elle fut importée par voie humaine depuis la Sierra Leone voisine. Une description spatio-temporelle du choléra au Mozambique démontre l'hétérogénéité de sa transmission et amène à questionner le concept d'endémicité du choléra. Depuis son importation en Haïti en octobre 2010, l'épidémie de choléra présente également une répartition spatiale et temporelle très hétérogène. Son importante rétractation en saison sèche et son absence d'enracinement significatif dans l'environnement laissent espérer la possibilité d'une élimination rapide à condition d'apporter une réponse ciblée à tous les foyers épidémiques du pays. Une stratégie d'élimination basée sur nos recommandations y est actuellement menée par le Ministère de la Santé, l'UNICEF et leurs partenaires. Après des résultats spectaculaires en 2013 et au premier semestre 2014, la situation s'est à nouveau dégradée pendant la saison des pluies. Une élimination du choléra dans saison sèche à venir demeure cependant réaliste si nous parvenons à convaincre et remobiliser les acteurs de terrainCholera is an epidemic acute watery diarrhea caused by toxigenic bacteria Vibrio cholerae O1. Its environment determinants have been at the source of a popular paradigm. Many recent control strategies have shown little efficiency in Africa or in Haiti, but they could be improved by a better comprehension of the epidemics dynamic. The bibliographic synthesis of environment influences on cholera in Africa highlights the limits of the environmental paradigm on this continent. A multidisciplinary study of the origin of cholera epidemic in Guinea in 2012 strongly suggests it was humanly imported from nearby Sierra Leone. A space-time description of cholera in Mozambique demonstrates heterogeneous transmission patterns and challenges the concept of cholera endemicity. Since its importation in Haiti in October 2010, cholera transmission also exhibits a marked spatio-temporal heterogeneity. Cholera important retraction during the dry season and its absence of significant establishment in the Haitian environment suggest it may be possible to rapidly eliminate cholera in the country, provided that every outbreak focus receives a targeted response. An elimination strategy based on our recommendations is currently implemented by Haitian Ministry of Health, UNICEF and their partners. After spectacular results in 2013 and during the first half of 2014, the situation has slowly deteriorated during the rainy season. However, cholera elimination during the coming dry season remains realistic provided that we succeed in persuading and remobilizing the partners present on the field
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Robb, Rhonda Rae. "Risk Factors for Pre-Post Monsoon Cholera Epidemics in Bangladesh from 1992-1994." PDXScholar, 2004. https://pdxscholar.library.pdx.edu/open_access_etds/1691.
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The primary objective of this thesis is to differentiate between the risk factors for pre-and post-monsoon cholera epidemics in rural Bangladesh by analyzing the complex interaction between select environmental, cultural/behavioral, and socioeconomic variables over space and time. In rural Bangladesh, cholera epidemics correspond with the annual monsoon: the first, and smallest, occurs between March and June, while the larger cholera peak occurs between September and December. The differences between the spatial and temporal patterns of seasonal cholera are analyzed, and the risk factors are calculated for pre-and post-monsoon cholera epidemics.
The theoretical approach that underlies this medical geographical study is disease ecology, which espouses that risk of disease is caused by an interaction between people and their environment. This thesis is structured around a holistic understanding that human-environment interactions are inseparable.
In Bangladesh, the monsoon season typically starts between May and June. The 1992 and 1993 cholera peaks occurred just before the monsoon in April and March respectively, while the 1994 cholera peak occurred between April and June. In 1992 and 1993 cholera incidence increased in the post-monsoon period, and peaked in October. The 1994 post-monsoon cholera peak occurred in November. There is a regular temporal pattern to cholera, as the peaks followed a seasonal pattern with the smaller epidemic occurring in the pre-monsoon period and the larger epidemic occurring in the post-monsoon period.
This study shows that there are different risks associated with pre-monsoon cholera epidemics and post-monsoon cholera epidemics. The two main risk factors associated with cholera incidence pre-monsoon were bari population (i.e., crowding) and a house located within the flood controlled area. These two variables were even more strongly associated with post-monsoon cholera incidence to a greater degree, along with a number of other variables including water use, sanitation practices, and socioeconomic status.
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Hayes, Edward. "Fragment based design of cholera toxin inhibitors." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.534749.
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Scobie, Tamara Susan. "The structure and function of cholera toxin." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/19281.
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COLUCCI, MANUELA. "Immunomodulatory properties of cholera toxin B subunit." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/1019.
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L'immunità innata antigene-non-specifica e l'immunità adattativa antigene-specifica collaborano per debellare i patogeni che invadono l'organismo tramite l'intervento delle cellule del sistema immunitario e delle loro molecole effettrici, che includono le proteine del complemento, gli anticorpi, le citochine e i fattori deputati alla lisi cellulare. Le risposte immunitarie adattative vengono indotte, coordinate e regolate dalle cellule dendritiche (DC). Le DC avviano le risposte immunitarie attivando i linfociti B e T naïve – che sono le cellule effettrici dell'immunità adattativa – e stimolando le cellule natural killer, che sono le principali cellule effettrici dell'immunità innata. Accanto al loro ruolo di collegamento tra immunità innata e adattativa, le DC hanno il delicato compito di limitare le risposte infiammatorie eccessive, che potrebbero causare danni tissutali, con lo scopo di prevenire l'insorgenza di reazioni indesiderate contro antigeni autologhi o innocui. A questo scopo, le DC inducono nei linfociti uno stato di “non-responsività” contro gli antigeni sia negli organi linfoidi primari che in quelli secondari, attraverso meccanismi che includono la delezione e l'induzione di cellule T regolatorie (Tregs). Dal momento che presentano questo ruolo centrale sia nell'immunità che nella tolleranza, le DC dimostrano di essere un candidato ideale come bersaglio di farmaci immunomodulanti.
Nel presente studio abbiamo esaminato la possibilità che la CTB ricombinante (rCTB) possa influenzare le funzioni delle DC in risposta alla stimolazione tramite toll-like receptors (TLR), rendendo le DC capaci di indurre il differenziamento di Tregs.
La CTB – la subunità B della tossina colerica – è un'efficace proteina trasportatrice a livello mucosale, in quanto facilita l'internalizzazione degli antigeni ad essa legati tramite l'interazione con il proprio recettore di membrana GM1, e favorisce l'attivazione delle risposte immunitarie dirette contro tali antigeni.
Inoltre è stato dimostrato che la CTB agisce come un immunosoppressore, dal momento che è in grado di inibire l'attivazione delle linee cellulari monocito-macrofagiche e di sopprimere le risposte di tipo Th1.
Le nostre ricerche dimostrano che la rCTB previene parzialmente la maturazione di DC derivanti da monociti (MDDC) indotta da lipopolisaccaride (LPS) e ne diminuisce la produzione di IL-12p70 senza influenzarne la produzione di IL-10. Le DC pretrattate con CTB e stimolate con LPS sono così in grado di promuovere l'induzione di cellule T scarsamente proliferanti che mostrano un'aumentata produzione di IL-10 associata ad una ridotta produzione di interferon-γ (IFN-γ) e ad analoghi elevati livelli di trasforming growth factor-b (TGF-β), quando paragonati a quelli delle cellule di controllo.
Le cellule T così indotte sono capaci di sopprimere la proliferazione di cellule T autologhe attivate, tramite la produzione di fattori solubili, come dimostrano gli esperimenti effettuati mediante Transwell o con anticorpi bloccanti il recettore dell'IL-10 (IL-10R) ed il TGF-β. Tutte queste caratteristiche rendono le cellule T indotte da DC condizionate con rCTB simili alle Tregs di tipo 1 (Tr1) producenti IL-10.Antigen-non-specific innate immunity and antigen-specific adaptive immunity synergize to eradicate invading pathogens through the actions of immune cells and their effector proteins, including complement, antibodies, cytokines and cytolytic factors. Adaptive immune responses are induced, coordinated and regulated by dendritic cells (DC). DC initiate immunity by the activation of naïve B and T cells - the effector cells of the adaptive immune system - and by the stimulation of natural killer cells - the crucial cellular instigators of innate resistance. Besides linking innate and adaptive immunity, DC limit excessive, tissue-damaging immune responses in order to prevent autoimmunity and non-essential reactions to innocuous agents through their ability to induce antigen-specific unresponsiveness of lymphocytes in primary and secondary lymphoid tissues by mechanisms that include deletion and induction of regulatory T cells (Tregs). Given the central role of these antigen presenting cells in immunity and tolerance, they are ideal therapeutic targets for pharmacological modulation of immune responses. In the present study, we examined the possibility that recombinant CTB (rCTB) may affect human DC functions in response to toll-like receptor (TLR) stimulation and may induce the generation of DC with the capacity to generate Tregs. CTB - cholera toxin B subunit - is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens, since it facilitates entry into the cell of the CTB-antigen complex by ligation of its surface receptor GM1. There is also good evidence that CTB acts as an immunosuppressant, as it is able to down-modulate human monocyte/macrophage cell line activation and to suppress Th1-type responses. Our findings show that rCTB partially prevents the lipopolysaccharide (LPS)-induced maturation process of monocyte-derived DC (MDDC) and decreases their interleukin-12p70 (IL-12p70) production with no relevant effect on IL-10 production. LPS-stimulated MDDC pre-treated with rCTB are able to promote the induction of low proliferating T cells, which show an enhanced IL-10 production associated with a reduced interferon-γ (IFN-γ) production and the same high levels of trasforming growth factor-β (TGF-β) as the control. These T cells suppress proliferation of activated autologous T cells. Transwell experiments and blockade of IL-10R and TGF-β showed that the immunomodulatory effect is mediated by soluble factors. Thus, T cells induced by rCTB-conditioned MDDC acquire a regulatory phenotype and activity similar to those described for IL-10 producing type 1 Tregs (Tr1).
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Balmforth, Matthew Royce. "Piggybacking on the cholera toxin : using cholera toxin B chain for the targeted delivery of proteins to motor neurones." Thesis, University of Leeds, 2017. http://etheses.whiterose.ac.uk/20115/.
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A significant unmet need exists for the delivery of biologics to the central nervous system for the treatment and understanding of neurodegenerative diseases. Naturally occurring toxoids such as the non-toxic B subunit of the cholera toxin have been considered as tools to meet this need. However, due to the complexity of tethering macromolecular drugs to toxins, and the inherent dangers of working with large quantities of recombinant toxin, no such route has been successfully exploited. Developing a method where toxoid and drug can be assembled immediately prior to administration could therefore be extremely useful. Using phage-display, two cholera toxin-binding antibody mimetics (Affimers) were identified that non-covalently associate with the non-GM1 binding face of the cholera toxin B subunit (CTB). The two unique interactions were characterised using a range of techniques to dissect the Affimer-CTB assembly process. Internalisation of the complex was demonstrated in tissue culture, and the system was used to deliver GFP to mammalian cells. Finally, the complex was shown to be successfully internalised into the motor neurones of the brainstem in a mouse model. A second route to modular assembly of a protein delivery system was also explored. By using a high affinity peptide staple, a cholergenoid-botulinum toxin chimera was produced that could be assembled in vitro and used to deliver the functional catalytic domain of botulinum neurotoxin to cultured neuronal cells.
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Чемич, Микола Дмитрович, Николай Дмитриевич Чемич, Mykola Dmytrovych Chemych, Андрій Олегович Сніцар, Андрей Олегович Сницарь, Andrii Olehovych Snitsar, Ірина Олександрівна Троцька, et al. "Випадок завезеної холери, викликаної V. cholerae О139, у Сумській області." Thesis, Видавництво СумДУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/3802.
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Said, Bengu. "Vibrio cholerae non-O1 and V. mimicus in diarrhoeal disease : a study of virulence factors." Thesis, Open University, 1995. http://oro.open.ac.uk/57564/.
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Saul-McBeth, Jessica. "Characterization of SipA, A Protein Important for Stress Responses in Vibrio cholerae." University of Toledo Health Science Campus / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=mco1544540466901883.
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Jablonski, Lynn McGonagle. "Development of a cloning system for gene expression in Pasteurella multocida." Diss., This resource online, 1993. http://scholar.lib.vt.edu/theses/available/etd-05042006-164516/.
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Giebultowicz, Sophia H. Emch Michael. "Cholera transmission in Bangladesh social networks and neighborhoods /." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2010. http://dc.lib.unc.edu/u?/etd,2956.
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Thesis (M.A.)--University of North Carolina at Chapel Hill, 2010.Title from electronic title page (viewed Jun. 23, 2010). "... in partial fulfillment of the requirements for the degree of Master of Arts in the Department of Geography." Discipline: Geography; Department/School: Geography.
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O'Neal, Claire J. "Structural studies of the cholera toxin catalytic subunit /." Thesis, Connect to this title online; UW restricted, 2005. http://hdl.handle.net/1773/8592.
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Chan, Wai-man, and 陳渭雯. "Development of edible vaccines against hog cholera virus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2003. http://hub.hku.hk/bib/B31227181.
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Vely, Frédéric. "Préparation et caractérisation d'anticorps monoclonaux anti-"Vibrio cholerae" O:1. Contributions à l'étude des bases moléculaires de la vibriocidie et à l'amélioration du diagnostic." Paris 5, 1993. http://www.theses.fr/1993PA05P215.
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Pandit, Kalyan Kumar. "Detection of serotype and potential virulence determinants in Pasteurella multiocida of different host origin." Thesis, University of Surrey, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306277.
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Webb, Jeanette Helen. "The role of ubiquitin during African swine fever virus infection." Thesis, University of Hertfordshire, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.363507.
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Jones, Huw Dylan. "The role of G-proteins in intracellular signalling mechanisms of wild oat (Avena fatua) aleurone." Thesis, University of Bristol, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337173.
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Caplet, Nathalie. "Cloning and characterisation of EpsD, a protein required for toxin secretion from Vibrio cholerae." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302104.
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Bonderup, Gerda. ""Cholera-Morbro'er" og Danmark : billeder til det 19. århundredes samfunds- og kulturhistorie /." Aarhus : Aarhus universitetsforlag, 1994. http://catalogue.bnf.fr/ark:/12148/cb36180664x.
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Hof, Suzanne Michelle. "Synthesis of inhibitors for the cholera family of toxins." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0011/NQ59600.pdf.
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Machin, Darren Christopher. "Engineering cholera toxin for the targeted delivery of oligonucleotides." Thesis, University of Leeds, 2016. http://etheses.whiterose.ac.uk/16635/.
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Half of the 20 best-selling prescription drugs of 2014 were large biologic therapeutics, however to date there have only been two licensed non-aptamer oligonucleotide drugs. Oligonucleotides have proven highly successful at modification of gene expression in the laboratory, but the lack of a robust delivery vehicle has largely prevented their transferal to clinical use. That role could be filled by cholera toxin, a protein produced by Vibrio cholerae, responsible for the diarrhoeal symptoms of cholera infection. Cholera toxin targets cells presenting GM1 ganglioside on their surface for endocytosis and carries a toxic payload to the endoplasmic reticulum (ER) by retrograde translocation. Several non-toxic variants of cholera toxin have been produced which are capable of carrying a cargo into cells, but to date it has not been tested for oligonucleotide delivery. The non-toxic subunit of cholera toxin responsible for endocytosis, CTB, was expressed in the absence of the toxic A subunit. CTB was site-specifically labelled with fluorescein using sortase A and shown to carry the payload into Vero cells. The endocytic pathway was able to be altered through modification of the protein sequence. Subsequently, a short RNA duplex was delivered to different locations in Vero cells by two subtly different CTB variants. Several strategies were then trialled to promote oligonucleotide release from CTB and export to the cytosol. While oligonucleotides conjugated via a disulfide bond were released in the ER, and a short hydrophobic peptide mediated export of an oligonucleotide-CTB complex from the ER, a combination of both was not observed. This study showed CTB has the potential to function as an effective delivery vehicle for therapeutic oligonucleotides, but also that there remains work to do and are hurdles to overcome to achieve this goal. It provides a platform for the development of CTB, or other similar proteins, for clinical use.
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Carrel, Margaret A. Emch Michael. "Relationships between flood control and cholera in Matlab, Bangladesh." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2007. http://dc.lib.unc.edu/u?/etd,1945.
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Thesis (M.A.)--University of North Carolina at Chapel Hill, 2007.Title from electronic title page (viewed Dec. 11, 2008). "... in partial fulfillment of the requirements of the degree of Master of Arts in the Department of Geography." Discipline: Geography; Department/School: Geography.
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SCIARAFFIA, ESTER. "Effects of cholera toxin on cells of immune system." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/1070.
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In questa tesi sono stati analizzati gli effetti della Tossina Colerica (CT) sulle cellule del sistema immunitario. In particolare, sono stati studiati i meccanismi di inibizione della proliferazione dei linfociti T CD4+ e CD8+ umani da parte della CT. E’ stato osservato che la CT è in grado di prevenire l’attivazione dei linfociti T nelle fasi precoci e tale inibizione coinvolge la modulazione dell’espressione delle molecole CTLA-4 e CD28. E’ stato osservato che la CT up-regola l’espressione delle molecole inibitorie CTLA-4 e down-modula le molecole costimolatorie CD28 sui linfociti T CD4+ e CD8+ resting. L’incremento dell’espressione delle molecole CTLA-4 da parte della CT gioca un ruolo nel controllare l’attivazione e la proliferazione dei linfociti T, infatti, abbiamo osservato che anticorpi bloccanti anti-CTLA-4 F(ab’)2 sono in grado di prevenire, anche se parzialmente, tale inibizione. I nostri studi hanno valutato, inoltre, la funzione di linfociti T pre-trattati con la CT e abbiamo osservato che essi sono in grado di inibire la proliferazione di linfociti T autologhi stimolati con anti-CD3. Abbiamo inoltre osservato che questo fenomeno è mediato dal rilascio di cAMP all’esterno delle cellule.
Alla luce di questi risultati, abbiamo analizzato gli effetti esercitati dall’cAMP extracellulare come primo messaggero su diversi tipi cellulari. L’cAMP extracellulare è in grado di inibire la proliferazione dei linfociti T ed è in grado di interferire con il differenziamento dei monociti in cellule dendritiche (DCs). Infatti, monociti differenziati in presenza di cAMP esogeno, non esprimono molecole CD1a e mantengono l’espressione di molecole CD14, acquisendo un fenotipo simile ai macrofagi. Tuttavia, le cellule generate in presenza di cAMP esogeno esprimono alti livelli di molecole MHC di classe II e di classe I e molecole costimolatorie CD86, mostrando un fenotipo attivato in grado di stimolare risposte T allogeniche. Inoltre, tali cellule non sono in grado di produrre TNF-α e IL-12, ma rilasciano quantità elevate di IL-6 e di IL-10. Monociti trattati con cAMP extracellulare hanno una capacità ridotta di indurre il differenziamento di linfociti T CD4+ che producono IFN-γ.
Infine, è stato investigato il meccanismo attraverso il quale il cAMP extracellulare interagisce con le cellule. Utilizzando diversi antagonisti dei recettori dell’adenosina, abbiamo osservato che gli effetti mediati dal cAMP extracellulare possono essere prevenuti. Tali risultati suggeriscono che l’cAMP sia trasformato in adenosina e che tale molecola, attraverso l’interazione con i suoi recettori, sia responsabile degli effetti mediati dal cAMP esogeno.In this study, we analysed the effects of Cholera Toxin (CT) on cells of immune system. In particular, the mechanisms underling the inhibition of T cell proliferation mediated by CT on human CD4+ and CD8+ T lymphocytes were analysed. We observed that CT prevents the early activation steps of T lymphocytes and that these effects involve the modulation of costimulatory molecules CTLA-4 and CD28. We observed that CT up-regulates the expression of the inhibitory molecule CTLA-4 in resting CD4+ and CD8+ T lymphocytes. The regulation of CTLA-4 expression by CT is at the transcriptional level. Indeed, in cells treated with CT we observed an increase of two mRNA variants coding for the membrane and the soluble CTLA-4 molecules. In parallel with the up-regulation of the inhibitory molecule CTLA-4, CT down-modulates the costimulatory molecule CD28 on CD4+ and CD8+ resting T cells. The increased expression of CTLA-4 plays a role in controlling T cell activation and function as blocking anti-CTLA-4 F(ab’)2 mAbs partially prevents the inhibition mediated by CT. We evaluated the function of CT-pre-treated CD4+ T lymphocytes and we observed that they are able to inhibit the proliferation of autologous T lymphocytes stimulated with anti-CD3 mAbs. It is interesting that this phenomenon is, at least in part, a result of the release of extracellular cAMP. Therefore, by analysing the direct effects exerted by extracellular cAMP as a primary messenger on different cell types, we found that extracellular cAMP inhibits T cell proliferation and that it is able to interfere with the differentiation of monocytes into DCs. Monocytes induced to differentiated into DCs in the presence of extracellular cAMP, do not express CD1a molecules and retain the expression of CD14 acquiring a macrophages-like phenotype. Furthermore, they strongly up-regulate MHC class I and class II and CD86 costimulatory molecules giving rise to an activated population able to stimulate allogeneic T cell response. In addition, they produce a distinct pattern of cytokines upon maturation stimuli, they are unable to produce TNFα and IL-12 and they release high amount of IL-6 and IL-10. Furthermore, monocytes differentiated in the presence of cAMP show a reduced capacity of inducing the differentiation of IFNγ producing CD4+ T lymphocytes. Finally, the mechanisms through which extracellular cAMP can be sensed by the cells were studied. By using different adenosine receptors antagonists, we found that an extracellular cAMP-adenosine pathway is involved in the effects mediated by exogenous cAMP, suggesting that extracellular cAMP acting as primary messenger can be sensed by the cells of immune system and can modulate their functions.
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Chow, Kwok-ming. "Cholera prevention as social control? : Hong Kong in the late 1960s /." Hong Kong : University of Hong Kong, 1997. http://sunzi.lib.hku.hk/hkuto/record.jsp?B18649981.
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Jahan, Nasrin. "Structural studies of Vibrio cholerae quorum sensing proteins." Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/2565.
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The spread of cholera is always associated with contaminated food or water and this is the reason this disease has been endemic in developing countries for centuries due to their lack of proper sanitation facilities and poor or no infrastructure for sewage systems. Cholera can spread quickly and sporadically after any natural disaster that destroys the sewage system or safe drinking water supply of both developed and undeveloped countries. In Southeast Asia in December 2004 and in Pakistan and Haiti 2010, cholera outbreaks followed the natural disasters; with most of the cholera victims being children. Although it is known that the best way to prevent cholera outbreak is the development of the infrastructure, provision of a safe drinking water supply and proper sanitation, this is a very long-term process, and most of the developing countries cannot afford such improvements. These situations can be made worse by natural disasters. Therefore there is a pressing need for the development of a cholera vaccine and there have been numerous research projects working towards this end for several decades. A few of them have been successful to date but because of the severe side effects and narrow range of protection, more effective and wider range vaccine development is still ongoing. In this study, crystallographic and enzymatic studies have been carried out on several novel proteins involved in the control of the production of the factors required for quorum sensing. Quorum sensing is a process in which bacterial cells communicate among themselves by the synthesis, release and detection of small chemical compounds called autoinducers. In this work, structural analysis was carried out on proteins involved in the synthesis and detection of the major autoinducer of Vibrio cholerae, named CAI-1. The crystal structure of CqsA involved in CAI-1 synthesis has been successfully solved and its enzymatic properties have been characterized. The structure of one domain of the cytoplasmic region of the CAI-1 receptor CqsS was also elucidated, and other domains were expressed. The crystal structure of another enzyme (VCA0859, an aldo-keto reductase) thought to have been involved in the synthesis of CAI-1 was also determined. Another protein named VCA0939 was also studied, due to its importance in biofilm development, and its ability to control quorum-sensing in an alternative pathway in the mutated version of pathogenic strains of V. cholerae that were responsible for the seventh cholera pandemic. The aim of this project was to understand the three dimensional structure of some proteins that are involved in quorum sensing and control of the expression of virulence genes for the pathogenesis of V. cholerae. Understanding the three dimensional structure of the proteins and the mode of autoinducer binding to its specific receptor could be highly valuable in the development of a chemical compound that could lead to the discovery of a novel drug with the ability to target cross species specification.
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Torres, Andre L. "An inexpensive, plant-derived, dual vaccine for rotavirus and cholera." Honors in the Major Thesis, University of Central Florida, 2009. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1333.
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This item is only available in print in the UCF Libraries. If this is your Honors Thesis, you can help us make it available online for use by researchers around the world by following the instructions on the distribution consent form at http://library.ucf.edu/Systems/DigitalInitiatives/DigitalCollections/InternetDistributionConsentAgreementForm.pdf You may also contact the project coordinator, Kerri Bottorff, at kerri.bottorff@ucf.edu for more information.Bachelors
Medicine
Biotechnology
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Burress, Helen. "Modulation of cholera toxin structure and function by host proteins." Doctoral diss., University of Central Florida, 2014. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/6251.
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Cholera toxin (CT) moves from the cell surface to the endoplasmic reticulum (ER) where the catalytic CTA1 subunit separates from the holotoxin and unfolds due to its intrinsic thermal instability. Unfolded CTA1 then moves through an ER translocon pore to reach its cytosolic target. Due to the instability of CTA1, it must be actively refolded in the cytosol to achieve the proper conformation for modification of its G protein target. The cytosolic heat shock protein Hsp90 is involved with the ER-to-cytosol translocation of CTA1, yet the mechanistic role of Hsp90 in CTA1 translocation remains unknown. Potential post-translocation roles for Hsp90 in modulating the activity of cytosolic CTA1 are also unknown. Here, we show by isotope-edited Fourier transform infrared (FTIR) spectroscopy that Hsp90 induces a gain-of-structure in disordered CTA1 at physiological temperature. Only the ATP-bound form of Hsp90 interacts with disordered CTA1, and its refolding of CTA1 is dependent upon ATP hydrolysis. In vitro reconstitution of the CTA1 translocation event likewise required ATP hydrolysis by Hsp90. Surface plasmon resonance (SPR) experiments found that Hsp90 does not release CTA1, even after ATP hydrolysis and the return of CTA1 to a folded conformation. The interaction with Hsp90 allowed disordered CTA1 to attain an active state and did not prevent further stimulation of toxin activity by ADP-ribosylation factor 6, a host cofactor for CTA1. This activity is consistent with its role as a chaperone that refolds endogenous cytosolic proteins as part of a foldosome complex consisting of Hsp90, Hop, Hsp40, p23, and Hsc70. A role for Hsc70 in CT intoxication has not yet been established. Here, biophysical, biochemical, and cell-based assays demonstrate Hsp90 and Hsc70 play overlapping roles in the processing of CTA1. Using SPR we determined that Hsp90 and Hsc70 could bind independently to CTA1 at distinct locations with high affinity, even in the absence of the Hop linker. Studies using isotope-edited FTIR spectroscopy found that, like Hsp90, Hsc70 induces a gain-of-structure in unfolded CTA1. The interaction between CTA1 and Hsc70 is essential for intoxication, as an RNAi-induced loss of the Hsc70 protein generates a toxin-resistant phenotype. Further analysis using isotope-edited FTIR spectroscopy demonstrated that the addition of both Hsc70 and Hsp90 to unfolded CTA1 produced a gain-of-structure above that of the individual chaperones. Our data suggest that CTA1 translocation involves a ratchet mechanism which couples the Hsp90-mediated refolding of CTA1 with extraction from the ER. The subsequent binding of Hsc70 further refolds CTA1 in a manner not previously observed in foldosome complex formation. The interaction of CTA1 with these chaperones is essential to intoxication and this work elucidates details of the intoxication process not previously known.Ph.D.
Doctorate
Molecular Biology and Microbiology
Medicine
Biomedical Sciences
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LIMA, BEATRIZ DE SOUZA. "LOVE IN THE TIME OF CHOLERA: AGGRESSIVENESS, SUBJECTIVITY AND CULTURE." PONTIFÍCIA UNIVERSIDADE CATÓLICA DO RIO DE JANEIRO, 2007. http://www.maxwell.vrac.puc-rio.br/Busca_etds.php?strSecao=resultado&nrSeq=9985@1.
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COORDENAÇÃO DE APERFEIÇOAMENTO DO PESSOAL DE ENSINO SUPERIORA presente tese tem como tema uma investigação sobre a participação da agressividade e da cultura nos processos de subjetivação e do tornar-se pessoa. Em um primeiro momento buscou-se estabelecer a distinção entre agressividade e violência no contexto da cultura, da teoria psicanalítica e na obra D.W. Winnicott. Em seguida efetuou-se um estudo sobre a teoria winnicottiana da agressividade que procurou compreender a sua evolução situando-a em relação à três contextos teóricos distintos: o inicial, o da teoria do desenvolvimento emocional e o dos objetos e fenômenos transicionais. Por fim, a partir do trabalho realizado pela ONG - Casa da Árvore, e dos conceitos de provisão ambiental, falha ambiental e tendência anti-social, elaborou-se uma reflexão sobre as manifestações agressivas e destrutivas, no âmbito de um dispositivo terapêutico que promove o atendimento coletivo de crianças de 6 a 12 anos, na comunidade do Morro do Chapéu Mangueira, na cidade do Rio de Janeiro. Defende-se a tese de que a promoção de uma política de atenção à infância resulta em um trabalho efetivo de prevenção em saúde mental, principalmente, no tocante à prevenção da violência, da delinqüência, dos distúrbios de conduta de caráter compulsivo e das doenças psicóticas.
The present thesis has as subject an inquiry on the participation of the aggressiveness and the culture in the processes of becoming a person. At a first moment was established the distinction between aggressiveness and violence in the context of the culture, the psychoanalysis theory and also considering the work of D.W. Winnicott. After that a study was done on the Winnicott´s theory of the aggressiveness that tries to understand its evolution pointing it out in relation to the three theoretical contexts: the initial context, the context of the emotional development theory and the context of the transicional objects and phenomena. Finally, from the experience of the non-governmental organization - Casa da Árvore - , and from the concepts of environmental provision and fails and of antisocial tendency, a reflection was elaborated on the manifestations of aggressiveness development disturbs, in the scope of a therapeutic device that promotes the collective assistance to children from 6 to 12 years old, in the community of the Morro do Chapéu Mangueira, in the city of Rio de Janeiro. We support that the promotion of politics of attention to childhood results in an extraordinary mental health prevention, mainly in regards to the prevention of the anti-social behavior and of the psychotic illnesses.
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Eckhoff, Grace. "Evaluation of a Novel Inaba Cholera Conjugate Vaccine in Mice." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:17295897.
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Vibrio cholerae is a non-invasive Gram-negative enteric pathogen that causes cholera, a severe dehydrating diarrheal illness of humans. Cholera is responsible for substantial morbidity and mortality in both endemic and epidemic settings. Current oral killed vaccines do not provide protection that lasts as long as natural cholera infection, and current cholera vaccines have greatly reduced efficacy in children, the population most affected by cholera in endemic areas. Protection against cholera appears to be mediated by immune responses that target the O-specific polysaccharide (OSP) of V. cholerae. Here we report analysis of the immunogenicity and protective efficacy in mice of a cholera conjugate vaccine containing V. cholerae O1 Inaba OSP conjugated to a recombinant immunogenic fragment of tetanus toxoid heavy chain (rTTHc). OSP-rTTHc induced prominent anti-OSP responses in these animals. Serum from vaccinated mice also provide protection in the infant mouse model of cholera infection. Our results suggest that a cholera conjugate might have development potential for evaluation in humans.