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De, Santis Paola. "Contagious bovine pleuropneumonia (CBPP) : studies on the disease and causative agent (Mycoplasma mycoides subsp. mycoides SC)." Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.425092.
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Mtui-Malamsha, Niwael Jesse. "Contagious bovine pleuropneumonia (CBPP) in the Maasai ecosystem of south-western Kenya : evaluation of seroprevalence, risk factors and vaccine safety and efficacy." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4379.
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Contagious bovine pleuropneumonia (CBPP) is a bovine bacterial disease of major economic importance in sub-Saharan Africa. Vaccination has been recommended to control the disease in endemic areas such as the Maasai ecosystems of Kenya and Tanzania; however, the currently used live attenuated vaccine has been reported to have poor vaccine safety and efficacy. To compare standard (current) and an improved (buffered) version of the live CBPP-vaccine, several epidemiological studies were carried out in Maasai cattle in Kenya between 2006 and 2008. Specifically, the aims were to estimate CBPP seroprevalence at herd and animal level; to identify risk factors for seroprevalence at both levels; to investigate the spatial distribution of seroprevalence; to compare post vaccination adverse events in cattle vaccinated with a standard and a buffered vaccine, and finally to compare efficacy of the two vaccines to induce seroconversion and to prevent development of clinical signs suggestive of CBPP. A cross-sectional study was carried out in 6872 cattle in 175 randomly selected herds from Loita and Mara divisions. A competitive ELISA revealed that 85% of the herds in the area had at least one seropositive animal and that seropositive herds were harbouring 11% seropositive cattle. A complement fixation test revealed that 46% of the herds had at least one seropositive animal and that seropositive herds were harbouring 4% seropositive cattle. A multivariable logistic regression analysis of the seroprevalence indicated that previous vaccination against CBPP, a history of CBPP outbreaks in the herd, animal age and the location of the herd in the division of Mara were positively correlated to seroprevalence. To investigate the observed difference in herd seroprevalence between the two divisions further, a spatial analysis was conducted. A SatScan test revealed clusters in Mara in areas identified by veterinary personnel as CBPP ‘hot spots’. A logistic regression using spatial information identified that location in the midland agro-ecological zone or close to a river and vaccination were positively associated with seroprevalence. To compare safety and efficacy of a standard and a buffered vaccine, two cohorts of approximately 40,000 cattle were used. The study showed that within 100 days post vaccination, 6.2 cattle per 1000 vaccinates developed adverse events, 4.1 of which were specifically attributable to vaccination and ranging from swelling of the tail to the tail sloughing off. This study revealed a slightly higher incidence of adverse events in cattle vaccinated with the buffered vaccine compared to the standard vaccine. A comparison of the efficacy of the two vaccines revealed that cattle vaccinated with the buffered vaccine had higher odds of seroconversion and lower odds of developing symptoms of CBPP, three and twelve months post vaccination respectively. The epidemiological studies conducted clearly show wide spread seroprevalence in the Maasai cattle. Given the (spatial) heterogeneity observed, control measures should probably be targeted in areas of increased risk (clusters). However, positive association of vaccination and seropositivity call for better diagnostics tests that can differentiate vaccinated from infected animals. Vaccination with buffered vaccine resulted in increased seroconversion, decreased clinical signs indicative of CBPP post vaccination and low seroprevalence post ‘outbreak’. Nevertheless, the increase in adverse events related to the buffered vaccine calls for further research into safer CBPP vaccines.
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Mulongo, Musa Matsanza. "Evaluation of lipoprotein Q and L-a-glycerol-3-phosphate oxidase of mycoplasma mycoides subs. mycoides (small colony) as virulence factors in contagious bovine pleuropneumonia (CBPP) infections." Thesis, Royal Veterinary College (University of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558979.
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Malafosse, Maxime. "La blockchain en support aux communs." Electronic Thesis or Diss., Aix-Marseille, 2022. http://www.theses.fr/2022AIXM0455.
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La blockchain et les communs sont deux concepts qui suscitent de plus en plus d’intérêt. Par des approches différentes, on prête à ces deux notions beaucoup d’espoir pour transformer notre société et répondre aux enjeux actuels de transition sociale et écologique. Pourtant peu de recherches les mettent en lien. D’autant plus que les travaux qui rapprochent la blockchain et les communs restent essentiellement théoriques. Nos recherches visent à mieux cerner comment la blockchain peut s’inscrire en support aux communs en situation réelle. Nous avons exploré plusieurs terrains qui incarnaient, de différentes manières, le rôle d’une technologie comme un outil au service d’une finalité collective. Nous avons commencé par observer la place centrale de la blockchain dans un dispositif sociotechnique de communs qui vise à produire et à autogérer la création monétaire (essai 1). Pour investir ce premier terrain de recherche, nous avons réalisé une étude de cas. Dans l’essai suivant, nous avons cherché à éclairer le rôle de la blockchain comme outil intégré dans un dispositif plus large d’expérimentation de communs de la donnée à l’échelle d’une ville (essai 2). Cette deuxième étude de cas a été murie par la réalisation d’une mission d’expertise de deux années dans un tiers lieu et s’est finalement focalisé sur le projet Européen DECODE. Enfin, notre dernier essai permet d’approfondir comment la blockchain pourrait permettre de soutenir économiquement les communs puisqu’elle bouleverse les perspectives de la monnaie par la démocratisation de ses formes alternatives, la facilitation de sa création et la complexification de son design (essai 3)Blockchain and the commons are two concepts that are attracting more and more interest. Through different perspectives, these two notions raise a lot of hopes to transform our society and to answer the current challenges of social and ecological transition. However, there is little research linking them. Especially since the work that brings blockchain and the commons together remains essentially theoretical. Our work aims to better understand how blockchain can support the commons in real life situations. We explored several fields that embodied, in different ways, the role of a technology as a tool in the service of a collective purpose. We began by observing the key role of the blockchain in a commons that aims to produce and self-manage monetary creation (essay 1). To invest this first research field, we conducted a case study. In the following essay, we aimed to shed light on the role of blockchain as a tool integrated in a larger device for experimenting the data commons at the scale of a city (essay 2). This second case study was matured by the realization of a two-year expertise mission in a third place and finally focused on the European project DECODE. Finally, our last essay builds on the results of the first essay and explores how blockchain could economically support the commons as it disrupts the prospects of money through democratizing its alternative forms, facilitating its creation, and increasing the complexity of its design (essay 3)
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Sidibe, Cheick Abou Kounta. "Epidémiologie de la Péripneumonie Contagieuse bovine(PPCB) dans les régions du Delta Central du Mali : évaluation des performances de deux tests de diagnostic pour analyser la dynamique de transmission et développement d'outils d'aide à la décision pour la surveillance et le contrôle." Thesis, Montpellier 2, 2012. http://www.theses.fr/2012MON20019/document.
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Deux tests sérologiques (test de fixation de complément (CFT) et l'ELISA de compétition (cELISA)) sont recommandés par l'OIE et utilisés couramment au Laboratoire Central Vétérinaire de Bamako parfois en parallèle dans le diagnostic et le dépistage de la péripneumonie contagieuse bovine (PPCB). La performance de ces tests a été estimée différemment par plusieurs auteurs dans des contextes épidémiologiques différents à partir de méthodes statistiques standards avec un statut sanitaire réel des animaux partiellement ou totalement connu. Dans un milieu où la PPCB est endémique avec différents stades d'évolution de la maladie, sachant que les tests sérologiques sont non parfaits (non gold standards), l'utilisation d'une approche bayésienne semblait appropriée pour une appréciation précise des paramètres de performance de tests qui sont la sensibilité et la spécificité, afin de mieux apprécier la prévalence de la maladie dans le cheptel bovin du delta central du Niger au Mali. Les résultats d'analyse de laboratoire des échantillons de terrain ont servi de bases de données importantes pour une analyse descriptive de la situation épidémiologique par appréciation des patrons de variations des principaux paramètres pouvant exercer une influence majeure sur la propagation de la PPCB. Ceci, dans le but d'aider à la réflexion sur la recherche d'outils et stratégies nouvelles dans le processus de prévention et d'éradication de la PPCB par le développement des modalités d'implantation d'une méthodologie innovante, pratique et efficace comme la qualification sanitaire troupeau concernant la PPCB dans un environnement d'élevage extensif. Cette thèse a permis de mieux définir les corrélations entre les deux tests, d'observer une meilleure sensibilité de cELISA par rapport à CFT permettant de justifier son utilisation seule dans un programme de dépistage à large échelle de la PPCB dans un milieu endémique. La démonstration dans l'étude de l'existence d'agrégation des animaux séropositifs à l'échelle du troupeau et aussi géographique montre qu'un système de qualification sanitaire troupeau pourrait jouer en collaboration avec le réseau national de surveillance épidémiologique vétérinaire, un rôle prépondérant dans la lutte ciblée et la maîtrise de la propagation de la PPCB au Mali. Mots clefs : PPCB-cELISA-CFT-Approche bayésienne-Agrégation-qualification sanitaire-BovinTwo serological tests (complement fixation test (CFT) and competitive ELISA (cELISA)) are recommended by the OIE and commonly used in Central Veterinary Laboratory of Bamako sometimes in parallel, in the diagnosis and screening for contagious (CBPP). The performance of these tests has been estimated differently by several authors in different epidemiological settings using standard statistical methods with a real status of animals partially or completely known. In an environment where CBPP is endemic and where different stages of disease are available, given that serological tests are not perfect (not gold standard), the use of Bayesian approach seemed appropriate for an accurate assessment of the performance parameters of tests which are the sensitivity, specificity and predictive values to better assess the prevalence of the disease in cattle in the central Niger delta in Mali. The results of laboratory analysis of field samples were used as large database for epidemiological analysis of the geographical distribution of seroprevalence and the influence of major risk factors for the spread of CBPP. This, in order to aid reflection on tools research and new strategies in the process of prevention and eradication of CBPP by developing for implementation of an innovative, practical and effective methodology as sanitary qualification of cattle. This thesis has helped define the correlations between the two tests, observing a better sensitivity of cELISA compared to CFT to justify its use only in a program of widespread testing of CBPP in an endemic environment. In this study, the proof of the existence of aggregation of seropositive animals across herds and geographical level shows that a sanitary qualification system of cattle can play in collaboration with the national network of veterinary epidemiological surveillance a leadership role in targeted control and mastery of the spread of CBPP in Mali.Keys words: CBPP- cELISA - CFT- Bayesian approach -Aggregation- Sanitary qualification –Bovine
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Hamsten, Carl. "Protein based approaches to understand and prevent contagious bovine pleuropneumonia." Doctoral thesis, KTH, Proteomik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-11108.
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Contagious bovine pleuropneumonia (CBPP) is a severe infectious disease caused by Mycoplasma mycoides subsp. mycoides small colony type (M. mycoides SC) and is a vast problem in Africa. Current CBPP prevention is based on attenuated live strain vaccines, but these are limited by factors such as short-term immunity, cold-chain dependence and retained virulence. CBPP can be diagnosed using post-mortem examination, identification of the agent using culture and PCR based methods as well as serological diagnostic methods, but the latter are generally not sensitive enough and there is also demand for an inexpensive, pen side field test.The research presented in this thesis was focused on using recombinantly expressed surface proteins from M. mycoides SC to characterize humoral immune responses to CBPP. Thereby candidate proteins to be used in development of serological diagnostic methods and possibly subunit vaccines could be identified. As a first step, five putative variable surface proteins of M. mycoides SC were expressed and purified from E. coli in Paper I. These proteins were analyzed using immunoblotting techniques and results showed that one protein, MSC_0364, was variably expressed on the surface of M. mycoides SC in vitro. Paper II presents expanded efforts including cloning and expression of 64 recombinant surface proteins and an assay for high throughput analysis of protein-specific IgG, IgA and IgM titers in hundreds of sera using a bead-based screening assay. The assay was evaluated by protein-specific inhibition experiments, comparisons to Western blotting and monitoring of immune responses over time in a study with sera taken from eight animals over 293 days from a previous vaccine trial.Papers III and IV present applications using the recombinant proteins and bead-based screening assay wherein proteins for diagnostic and vaccine development were identified. In Paper III, the assay was used to screen 61 proteins using well-characterized serum samples from cattle with CBPP and healthy controls, resulting in selection of eight proteins suitable for diagnostic use. These proteins were combined and evaluated in a proof-of-concept ELISA with a discriminative power that enabled 96% correct classification of sera from CBPP-affected and CBPP-free bovines. Paper IV reports the results and protein-specific analyses of a vaccine trial using the recombinant putative variable surface proteins presented in Paper I as a subunit vaccine. The vaccine conferred no protection, but a weak vaccine response could not be excluded as the cause of failure. In an effort to identity other protein candidates to be used in a subunit vaccine, protein-specific analysis of humoral immune responses elicited by the currently approved live strain vaccine, T1/44, were investigated. Here, five proteins with high IgG titers associated to immunity were identified: LppQ, MSC_02714, MSC_0136, MSC_0079 and MSC_0431. These proteins may be important in the development of a novel subunit vaccine against CBPP.QC 20100719
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Kronekova, Zuzana. "Assembly of mitochondrial ubiquinol-cytochrome c oxidoreductase complex in yeast Saccharomyces cerevisiae: The role of Cbp3p and Cbp4p assembly factors." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2005. http://nbn-resolving.de/urn:nbn:de:swb:14-1122027648324-54732.
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Ubiquinol-cytochrome c reductase (complex III) is a central component of the respiratory chain of the inner mitochondrial membrane. It transfers electrons from reduced ubiquinone to ferricytochrome c. Correctly assembled and functional complex III is an essential prerequisite for oxidative energy metabolism. Complex III deficiency has been reported to be associated with several neurodegenerative diseases. Formation and assembly of complex III requires a multitude of specific nuclearly encoded proteins. For example, gene specific translational activators for cytochrome b synthesis as well as three non-subunit proteins, which are important for assembly and/or stability have been detected. The role of Bcs1p in assembly of Rieske FeS protein and Qcr10p into complex III has been clasified recently. The role of the two putative chaperones, Cbp3p and Cbp4p, is not known. In spite of the similar phenotype of cbp3D and cbp4D strains, that suggests the role of both proteins in the same step of complex III assembly, we were able for the first time to demonstrate differences on the molecular level between both deletion mutants. We show by BN-PAGE that cbp3D and cbp4D mutants are disturbed in complex III assembly and accumulate intermediate-sized forms of the complex. Moreover deletion of CBP3 interferes with the formation of complex III/IV supracomplexes. Our studies show that Cbp3p and Cbp4p interact and are present in high molecular weight complexes, some of which might represent intermediates of complex III assembly. Overexpression of Cbp4p cannot substitute for the function of Cbp3p, but high level expression of Cbp3p can partially compensate for the lack of Cbp4p. Because lipids play an important role for complex III assembly and stability, we analysed the mitochondrial lipid composition of cbp3D and cbp4D mutants. Our data show that mitochondria of both mutants exhibit a wild type-like lipid composition, that favors the idea that Cbp3p and Cbp4p are specific assembly factors for complex III rather than components of the mitochondrial lipid metabolism. By complementation studies we have shown that Cbp3 proteins of S. cerevisiae, S. pombe and human are (partially) functional homologues. A yeast model based on chimeric constructs of S. cerevisiae and human proteins was constructed, which allows to test the pathogenicity of human mutations. To define the role/s of Cbp3p and Cbp4p in the assembly pathway of complex III, interactions of selected subunits with both assembly factors were analysed by TAP- or co-immunoprecipitation. Based on the results of Cbp3p and Cbp4p topologies, BN-PAGE analysis of null mutant strains and interaction studies a model for complex III assembly and the roles of Cbp3p and Cbp4p in this process are proposed. I present a hypothesis, according to which Cbp3p and Cbp4p form a ?scaffold? for the assembly of all three putative sub-complexes, may act independently in the first steps of bc1 complex assembly (e. g. the formation of sub-complexes) and interact together to assist the final assembly of sub-complexes into a mature enzymeDer Ubiquinol-Cytochrom c Reductase (Komplex III) ist eine zentrale Komponente der Atmungskette der inneren Mitochondrienmembran. Er transferiert Elektronen von reduziertem Ubiquinon auf Ferricytochrom c. Der korrekt assemblierte und funktionale Komplex III ist eine essenzielle Voraussetzung für den oxidativen Energiemetabolismus. Komplex III Defizienz ist assoziiert mit verschiedenen neurodegenerativen Krankheiten
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Gruschke, Steffi. "Early steps in the biogenesis of the bc1 complex in yeast mitochondria : The role of the Cbp3-Cbp6 complex in cytochrome b synthesis and assembly." Doctoral thesis, Stockholms universitet, Institutionen för biokemi och biofysik, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-81033.
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The inner membrane of mitochondria harbors the complexes of the respiratory chain and the ATP synthase, which perform the key metabolic process oxidative phosphorylation. These complexes are composed of subunits from two different genetic origins: the majority of constituents is synthesized on cytosolic ribosomes and imported into mitochondria, but a handful of proteins, which represent core catalytic subunits, are encoded in the organellar DNA and translated on mitochondrial ribosomes. Using yeast as a model organism, I investigated the mitochondrial ribosomal tunnel exit, the region of the ribosome where the nascent chain emerges and that in cytosolic ribosomes serves as a platform to bind biogenesis factors that help the newly synthesized protein to mature. This study provided insights into the structural composition of this important site of mitochondrial ribosomes and revealed the positioning of Cbp3 at the tunnel exit region, a chaperone required specifically for the assembly of the bc1 complex. In my further work I found that Cbp3 structurally and functionally forms a tight complex with Cbp6 and that this complex exhibits fundamental roles in the biogenesis of cytochrome b, the mitochondrially encoded subunit of the bc1 complex. Bound to the ribosome, Cbp3-Cbp6 stimulates translation of the cytochrome b mRNA (COB mRNA). Cbp3-Cbp6 then binds the fully synthesized cytochrome b, thereby stabilizing and guiding it further through bc1 complex assembly. The next steps involve the recruitment of the assembly factor Cbp4 to the Cbp3-Cbp6/cytochrome b complex and presumably acquisition of two redox active heme b cofactors. During further assembly Cbp3-Cbp6 is released from cytochrome b, can again bind to the ribosome and activate further rounds of COB mRNA translation. The dual role of Cbp3-Cbp6 in both translation and assembly allows the complex to act as a regulatory switch to modulate the level of cytochrome b synthesis in response to the bc1 complex assembly process.At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 4: Manuscript.
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Cummings, Cory R. "The Anatomy of CBPR: A Case Study of CBPR Implementation for Health Promotion with the Peer Community." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4966.
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This case study is a qualitative examination of a health promotion project conducted in collaboration with members of the mental health peer community. More specifically, it explores the community based participatory research (CBPR) implementation process used to conduct this health promotion project to gain a deeper understanding of the mechanisms at work in the implementation process. While there has been considerable attention to the principles that guide CBPR (Braun et al., 2012; Israel et al., 2008; LaVeaux & Christopher, 2009), there remains important work to be done in bridging these principles to implementation; what processes or mechanisms translate these principles to action. Four mechanisms were initially proposed by this writer, derived from extant literature in this area (Wallerstein & Duran, 2003). These provided the initial framework for analyzing the data gathered throughout the case study. The case report discusses the findings of how these initially proposed mechanisms have been transformed and redefined in the context of this case. The resultant mechanisms, knowledge sharing, power sharing, task sharing, resource sharing, and shared purpose (there are five, as one additional new mechanism emerged in the analysis), are described with examples of how they were reflected in this case. Implications for these findings for CBPR research, collaborative health promotion with the mental health peer community, and the social work profession are shared.
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Islas-Osuna, Maria A. "Genetic analysis of the Cbp1-COB mRNA interaction and the role of Cbp1 in translation of COB RNAs." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/279945.
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Mitochondria are the organelles where respiration occurs. The yeast mitochondrial genome encodes only 8 proteins, therefore the organelle depends on the nuclear genome for many proteins required in different steps of mitochondrial gene expression. Regulation of mRNA stability, processing and translation are important steps in gene expression within the mitochondrion. Cbp1, a protein encoded by the nuclear gene CBP1, is required specifically for stabilization of precursor and mature cytochrome b (COB) RNA, which is encoded in the mitochondrial genome. Previous work identified a cis-element, CCG, in the 5' untranslated region (UTR) of COB, that is critical for the Cbp1-dependent stability of COB mRNA. Mutation of any single nucleotide resulting in an A̲CG, CA̲G or CCU̲ triplet causes destabilization of COB mRNA and concomitant loss of respiratory capability. In the present study, suppressors were selected in the CCU strain in an effort to define important sites in Cbp1 for protection of COB mRNA. The mitochondrial mutant strain CCU is conditional; it grows slowly at 25°C but does not grow at 18°C or 33°C on the non-fermentable carbon source glycerol. Twelve dominant suppressors in CBP1 were obtained. They define two main groups, based on the pattern of growth on glycerol at different temperatures. The CBP1-encoded suppressors make strains containing the mitochondrial CCU̲ mutation respiratory competent at 33°C by allowing accumulation of mature COB mRNA. Suppressors that map to the carboxyl half of Cbp1, such as S289G, S330R, Q358K, Q358R, L489W, K532M, D533Y and I638M, rescue the temperature-sensitive (ts) phenotype caused by the CCU̲ mutation. The suppressors that map to the amino half of Cbp1, such as K205R, E241G, I249T, N281D and I293L, rescue the ts phenotype to a lesser extent than the suppressors that map to the carboxyl half of Cbp1. These results suggest that the two halves of Cbp1 have different functions in the processing and stability of COB transcripts. The hypothesis that Cbp1 has a role in translation of cytochrome b (COB) mRNA was not testable previously, since disruption of CBP1 results in instability and degradation of COB mRNA. In a Δpet127 strain, COB precursor mRNA is not processed to the mature 5' site and thus accumulates to levels equivalent to that of the wild-type mature mRNA (Wiesenberger and Fox, 1997). Null alleles of pet127 were selected as suppressors of A̲CG and CCU̲ mutations in COB. COB precursor mRNA levels in these strains were similar to the Δpet127 strain with a wild-type mitochondrial genome (Chen et al., 1999). In the present study, the effect of deleting CBP1 in a Δpet127 strain was measured. Strain Δcbp1 Δpet127 accumulated no mature COB mRNA but high levels of COB precursor mRNA. The levels of precursor mRNA in the Δcbp1 Δpet127 strain were 3-fold higher than in wild-type strain and approaching 60% of wild-type mature levels (wild-type COB precursor is 18% of mature COB mRNA). Absolutely no apocytochrome b protein was detected in the Δcbp1 Δpet127 strain. This result suggests that Cbp1 is required for translation of the COB message. Future experiments to determine the role of Cbp1 in the translation of COB mRNA are described.
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Joshi, Kaushal V. "Novel Neuroprotectants for Sarin plus CBDP induced convulsions." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1253321185.
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Corral, Rego Lía. "Validación del Cuestionario de Sesgos Cognitivos para la Psicosis (CBQp): Relación con sintomatología, insight y neurocognición." Doctoral thesis, Universitat Rovira i Virgili, 2019. http://hdl.handle.net/10803/670511.
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Introducció: Els biaixos cognitius són clau en la formació i manteniment dels deliris en la psicosi. El Cognitive Biases Questionnaire for Psychosis (CBQp) avalua cinc tipus de biaixos cognitius en la psicosi. L'objectiu d'aquest treball es validar la versió espanyola del CBQp, i estudiar la relació d'aquests biaixos cognitius amb la simptomatologia psicòtica, l’insight i la neurocognició. Material i mètode: La versió espanyola autoritzada del CBQp va ser obtinguda segons el procés de traducir-retrotraducció. La mostra va estar composta per 171 subjectes amb diagnòstics de psicosis. Una anàlisi factorial confirmatòria (AFC) va testar tres models alternatius del constructe. Es van dur a terme comparacions entre pacients amb psicosis i un grup control (N = 30) en relació a les subescales del CBQp. L'associació entre els biaixos del CBQp, les escales d’insight clínic (SUMD) i cognitiu (BCIS), les avaluacions de la simptomatologia psicòtica (PANSS i PDI) i la bateria neurocognitiva MATRICS va ser estudiada mitjançant correlació, diferència de mitjanes i regressions lineals. Resultats: En l’AFC, el CFI va mostrar valors entre 0.94 i 0.95 per als models de 1, 2 i 5 factors, amb valors de RMSEA de 0.031 i 0.029. La fiabilitat del CBQp va ser de 0.87. Els subjectes amb psicosis van puntuar significativament més alt en tots els biaixos cognitius, a excepció de Catastrofisme i Salt a conclusions, en comparació amb el grup control. Es van obtenir associacions entre els biaixos cognitius i les escales d'auto-certesa i insight cognitiu de la BCIS, les escales de malestar, preocupació, convicció i total del PDI, així com amb la simptomatologia positiva avaluada mitjançant la PANSS. El CBQp es va relacionar amb el rendiment cognitiu general avaluat mitjançant la MATRICS, més concretament, amb Velocitat de processament, Solució de problemes i Cognició social. Conclusions: La versió espanyola del CBQp ha mostrat una adequada fiabilitat i validesa. Un model d'1 factor podria ser més adequat per a explicar el constructe de l'escala, suggerint que el CBQp avalua un biaix de pensament general. Els biaixos avaluats pel CBQp implicarian major presència de deliris, malestar, convicció i preocupació respecte a aquests, major simptomatologia positiva, així com un pitjor insight cognitiu i un pitjor rendiment neurocognitiu general.Introducción: Los sesgos cognitivos son clave en la formación y mantenimiento de los delirios en la psicosis. El Cognitive Biases Questionnaire for Psychosis (CBQp) es un cuestionario que evalúa cinco tipos de sesgos cognitivos en la psicosis. El objetivo de este trabajo es validar la versión española del CBQp, y estudiar la relación de dichos sesgos con la sintomatología psicótica, el insight y la neurocognición. Material y método: La versión española autorizada del CBQp fue obtenida mediante traducción-retrotraducción. La muestra estuvo compuesta por 171 sujetos con diagnósticos de psicosis. Un análisis factorial confirmatorio (AFC) testó tres modelos alternativos del constructo. Se llevaron a cabo comparaciones entre pacientes con psicosis y un grupo control (N = 30) en relación a las subescalas del CBQp. La asociación entre los sesgos del CBQp, el insight clínico (SUMD) y cognitivo (BCIS), la sintomatología psicótica (PANSS y PDI) y la batería neurocognitiva MATRICS fue estudiada mediante correlación, diferencia de medias y regresiones lineales. Resultados: En el AFC, el CFI mostró valores entre 0.94 y 0.95 para los modelos de 1, 2 y 5 factores, con valores de RMSEA de 0.031 y 0.029. La fiabilidad del CBQp fue de 0.87. Los sujetos con psicosis puntuaron significativamente más alto en todos los sesgos cognitivos, a excepción de Catastrofismo y Salto a conclusiones, en comparación con el grupo control. Se obtuvieron asociaciones entre los sesgos cognitivos y las escalas de auto-certeza e insight cognitivo de la BCIS, las escalas de malestar, preocupación, convicción y total del PDI, así como con la sintomatología positiva evaluada mediante la PANSS. El CBQp se relacionó con el rendimiento cognitivo general evaluado mediante la MATRICS, y más concretamente con Velocidad de procesamiento, Solución de problemas y Cognición social. Conclusiones: La versión española del CBQp ha mostrado una adecuada fiabilidad y validez. Un modelo de 1 factor podría ser más adecuado para explicar el constructo de la escala, sugiriendo que el CBQp evalúa un sesgo de pensamiento general. Los sesgos evaluados por el CBQp implicarían mayor presencia de delirios, malestar, convicción y preocupación respecto a éstos, mayor sintomatología positiva, así como un peor insight cognitivo y peor rendimiento neurocognitivo general.
Introduction: Cognitive biases are key factors in the development and maintenance of delusions in psychosis. The Cognitive Biases Questionnaire for Psychosis (CBQp) evaluates five types of cognitive biases that are relevant in psychosis. The aim of this study is to validate the Spanish version of the CBQp, and to study the relationship between these biases and psychotic symptoms, insight and neurocognition. Materials and methods: The Spanish authorized version of the CBQp was obtained by a translation and back-translation procedure. A sample of 171 patients with different diagnoses of psychosis was included. A confirmatory factorial analysis (CFA) tested three different models of the construct. Comparisons of CBQp scales were analysed between patients with psychosis and a control group (N = 30). Associations between the CBQp biases, clinical and cognitive insight (SUMD and BCIS), symptoms (PANSS and PDI) and neurocognition (MATRICS), were studied by correlation and means differences and linear regressions. Results: CFA showed CFI values of 0.94 and 0.95 for the models with 1, 2 and 5 factors, with RMSEA values of 0.031 and 0.029. The reliability of the CBQp was 0.87. When compared with the group of healthy subjects, patients with psychosis scored significantly higher in all cognitive biases, except in Catastrophising (Cat) and Jumping to conclusions (JTC). Associations between cognitive biases and the self-certainty and the total cognitive insight scale of the BCIS were found. In the same way, associations between conviction, distress, preoccupation and total scales of the PDI and cognitive biases were found. The CBQp was also related with positive symptoms evaluated with the PANSS, and with general cognitive performance, specifically with Processing speed, Problem solving and Social cognition. Conclusions: The Spanish version of the CBQp shows high reliability and adequate internal consistency. A one-factor model might be more appropriate for explaining the construct of the scale, suggesting that the CBQp evaluates a general thinking bias rather than different cognitive errors. Cognitive biases involved a greater frequency of delusions, distress, conviction, and preoccupation, and more positive symptoms, as well as worse cognitive insight and worse global neurocognitive performance.
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ARVELO, FRANCISCO. "Approche biologique du cancer bronchique a petites cellules (cbpc)." Paris 6, 1990. http://www.theses.fr/1990PA066381.
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Dans ce travail nous avons essaye de definir de marqueurs tumoraux qui pourraient avoir une signification clinique dans le pronostic et la prediction de la sensibilite au traitement antitumoral a partir de lignees tumorales etablies sur souris nude. Dans la premiere partie, nous avons procede a l'analyse des marqueurs tumoraux par l'expression des oncogenes et de genes. Les resultats montrent que les cbpc sont heterogenes quant a l'expression des oncogenes et de genes. Dans la deuxieme partie, nous avons aussi etudie la chimiosensibilite de cbpc aux drogues antitumorales. Les tumeurs cbpc ont montre une grande chimiosensibilite aux traitements therapeutiques, mais ne sont pas chimiocurables lorsqu'ils sont implantes chez la souris nude, reproduisent ainsi les observations faites chez les patients d'ou les tumeurs ont ete obtenus. Finalement, nous avons etabli 5 lignees cellulaires in vitro a partir de cbpc etablis sur souris nude. Les cellules in vitro gardent des caracteristiques similaires aux tumeurs dont elles sont originaires
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Weber, Eric Renato. "Partial purification and biochemical characterization of CBP1 from Saccharomyces cerevisiae." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185644.
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The product of the yeast nuclear gene CBP1 is a mitochondrial protein which is necessary for the stability of the mitochondrial-encoded cytochrome b (cob) messenger RNA. In this dissertation I describe the partial purification, and the biochemical characterization of the CBP1 protein. Using a monoclonal antibody directed against CBP1, I have shown that CBP1 is a mitochondrial protein. I found that CBP1 was undetectable in a crude mitochondrial fraction isolated from a wild-type strain. However, a 66 kDa immunoreactive peptide was detected in a purified mitochondrial fraction, and was not present in a control strain. That CBP1 is a mitochondrial protein and contains an amino terminal leader peptide which is removed during import was confirmed by in vitro import of ³⁵S-labeled CBP1 into isolated mitochondria. I found that the mature protein product was 66 kDa, whereas the precursor protein migrated with the mobility of a 68 kDa polypeptide. This was in contrast to the published DNA sequence from which one can derive a molecular weight of 76 kDa for CBP1. It was determined from electrophoretic analysis of a nested group of carboxyl-terminal truncated peptides which were translated in vitro, that this aberrant electrophoretic mobility is due to a property of the carboxyl terminal region of the primary sequence which contains numerous basic residues. Having identified the CBP1 gene product in wild-type yeast, I wanted to determine the role of CBP1 in stabilizing the cob transcript. Using wild-type mitochondrial extracts containing CBP1, and extracts from a bacterial strain overexpressing CBP1, I tested different substrates derived from the 5'-untranslated leader of cob in three different types of assays; gel retardation, RNA-protein UV-crosslinking, and in scission assays in which I examined the possibility that CBP1 is responsible for generating the mature 5'-end of the cob mRNA. I was unable to show a direct interaction between CBP1 and the 5'-untranslated leader of cob mRNA in vitro. However, I was able to identify an exonuclease activity in a purified mitochondrial fraction from a wild-type yeast strain, which was not present in a control strain which harbored a deletion in the CBP1 gene.
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Mayer, Stephen Armond. "Carbon catabolite repression of yeast CBP1 mRNA 3' end formation." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185336.
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CBP1 is a yeast nuclear gene encoding a mitochondrial protein that stabilizes the 5' end of cytochrome b (cob) pre-mRNA. Cytochrome b is the only mitochondrially synthesized component of the respiratory chain Complex III. Since the nuclearly-encoded subunits of this complex are regulated at the transcriptional level by catabolite repression, we hypothesized that CBP1 might be similarly regulated. To test the idea that transcriptional regulation of CBP1 could coordinate an increase in cytochrome b mRNA stability with an increase in nuclearly-encoded Complex III subunit production, we characterized the change in abundance of CBP1 mRNA during derepression on a non-fermentable carbon source. Poly A⁺ RNA from derepressed yeast was examined by Northern analyses with cRNA probes from CBP1. Both 2.2 kb and 1.3 kb transcripts were detected. The 1.3 kb mRNA lacks approximately 900 base-pairs of the 3'-end of the 2.2 kb mRNA, which encodes the carboxyl-terminal 250 amino acid residues of the CBP1 coding sequence. Northern analyses of RNA isolated from deletion/insertion mutants of CBP1 and from strains which overexpress CBP1 mRNA demonstrated that both mRNAs are transcribed from the CBP1 gene. Furthermore, we have demonstrated that the levels of the two CBP1 mRNAs are reciprocally regulated by the carbon source in the growth medium. Having proposed that regulation of 3' end formation dictates the amount of each CBP1 transcript we now show that a 146 bp fragment from the middle of CBP1 is sufficient to direct carbon source-regulated production of two transcripts when inserted into the yeast URA3 gene. This fragment contains seven polyadenylation sites for the wild-type 1.2 kb mRNA, as mapped by sequence analysis of CBPl cDNA clones. Deletion mutations upstream of the polyadenylation sites abolished formation of the 1.2 kb transcript, whereas deletion of three of the sites only led to a reduction in abundance of the 1.2 kb mRNA. Though none of the experiments showed whether the 1.2 kb mRNA is formed solely by 3' processing, or if processing at this site is coupled to premature transcription termination, our results do indicate that regulation of the abundance of both CBP1 transcripts is contro11ed by elements in a short segment of the gene that directs 3' end formation of the 1.2 kb transcript, a unique case in yeast.
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Delvecchio, Manuela. "Mécanisme de régulation de l'acétyltransférase p300/CBP." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00631344.
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Le p300/CBP acétyltransférase est un co-activateur transcriptionnel très important qui est impliqué dans la régulation d'un grand nombre de processus biologiques, comme la transcription d'ADN, le développement et l'immunité innée. Jusqu'à présent, le rôle de p300/CBP dans la régulation de l'expression des gènes a été largement étudiée, mais les mécanismes qui régulent son activité enzymatique sont encore peu connus. Des études ont montré que le dysfonctionnement de p300/CBP est associé à plusieurs formes de cancer et de maladies neurodégénératives. Dés lors, chaque progrès concernant les mécanismes de régulation de p300/CBP est devenu primordial pour le développement de nouvelles thérapies. Le 'noyau' de p300/CBP contient deux domaines pour la reconnaissance des modifications post-traductionnelles (MPTs), un bromodomaine et un PHD finger (le module BP), adjacent à un domaine HAT (ou domaine histone acétyltransférase). Plusieurs enzymes, modifiant la chromatine, contiennent des domaines de reconnaissance des MPTs. Fréquemment des groupements particuliers de ces domaines sont très conservés et liés, au sein de la même protéine ou du même complexe protéique, suggérant qu'ils réalisent des fonctions coordonnées. Ces domaines adjacents peuvent agir en concertation dans la reconnaissance simultanée de différents MPTs ou peuvent exercer des fonctions différentes de celles qui sont effectuées par ces deux domaines particuliers, tels que les fonctions de régulation enzymatique. Plusieurs études suggèrent que les cycles acétylation/désacétylation dans la boucle d'auto-inhibition, à l'intérieur du domaine HAT, jouent un rôle important dans la régulation de l'activité enzymatique de p300/CBP. La proximité du module BP et du domaine HAT suggère que la spécificité de liaison, appartenant au module BP, peut être intrinsèquement liée à la régulation de l'activité du domaine HAT. L'objectif de ma thèse est de déterminer le rôle du module BP dans la régulation de l'activité du domaine HAT. Je propose que le module BP soit impliqué dans la régulation de p300/CBP de deux façons. La première consiste à établir un lien avec le domaine HAT qui stabilise la conformation auto-inhibée de l'enzyme. La deuxième exige que le module BP joue un rôle dans le choix des substrats de p300/CBP. J'ai été en mesure de montrer que BP peut se lier au domaine HAT et à la chromatine modifiée et qu'il peut reconnaître les modifications effectuées par p300/CBP lui-même. Les données obtenues indiquent que le module BP peut être impliqué dans la régulation de l'activité de p300/CBP et dans son ciblage à la chromatine.
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Klein, Fabrice. "Etudes structurales des interactions CBP-récepteurs nucléaires." Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13241.
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Les récepteurs nucléaires (NRs) forment une famille de facteurs de transcription dont l'activité est contrôlée par la fixation de ligands. La liaison à un ligand agoniste permet le recrutement de coactivateurs transcriptionnels, comme les p300/CREB‑BindingProtein (p300/CBP) et les p160/Steroid‑Receptor‑Coactivator (p160/SRC). Ces protéines possèdent plusieurs motifs LxxLL (L = Leucine ; X = n'importe quel acide aminé), responsables de l'interaction aux NRs. Nous avons caractérisé le domaine de CBP interagissant aux LBDs et co‑cristallisé un complexe de l'extrémité Nterminale de CBP (Nter‑CBP) et du LBD du Peroxisome Proliferator‑Activated Receptor gamma (lbd‑PPARg). La mauvaise qualité des cristaux de Nter‑CBP/lbd‑PPARg n'a pas permis de déterminer la structure du complexe. L'étude de Nter‑CBP par résonance magnétique nucléaire (RMN) montre que ce fragment isolé est peu structuré. Son interaction aux LBDs de trois NRs - PPARg, Retinoid X Receptor alpha (RXRa) et Estrogen Related Receptor gamma (ERRg) - a été étudiée par RMN. En raison d'une forte atténuation du signal des résidus impliqués dans l'interaction aux LBDs, la structure du fragment de mCBP en complexe à un LBD n'a pu être résolue, mais la zone d'interaction a été cartographiée : les résidus de CBP impliqués dans l'interaction représentent deux fragments discontinus, délimités par les acides aminés (31 à 38) et (61 à 80), la zone (61 à 80) contenant un LxxLL. L'interaction de fragments de CBP ou de SRCs aux LBDs de PPARg et RXRa a été étudiée de façon comparative par résonance plasmonique de surface (SPR) et par électrophorèse en conditions natives (N‑PAGE). Les résultats montrent l'existence d'interactions préférentielles entre RXRa et les SRCs, et entre PPARg et CBP. Les conclusions de nos travaux suggèrent que CBP puisse être recruté directement par l'hétérodimère PPARg/RXRa, ce qui pourrait jouer un rôle dans la permissivité de cet hétérodimèreNuclear receptors form a large family of transcription factors, whose activities are often controled by the fixation of small ligands. Binding to an agonist ligand allows the recruitment of transcriptional coactivators, like the p300/CREB‑BindingProtein (p300/CBP) or the p160/Steroid‑Receptor‑Coactivator (p160/SRC). Those coactivators possess several LxxLL motifs (L = Leucine ; X = any aminoacid), mainly responsible for the interaction with NRs. We characterized the aminoterminal (Nter) domain of CBP responsible for the interaction with NR Ligand Binding Domains (LBDs) and cocrystallized it together with the Peroxisome Proliferator‑Activated Receptor gamma LBD (lbd‑PPARg). The poor diffraction properties of the crystals did not allow us to solve the structure of this (Nter-CBP/lbd-PPARg) complex. Nuclear Magnetic Resonance (NMR) experiments demonstrate that Nter-CBP is poorly structured on its own. Its interaction with the LBDs of 3 different NRs - PPARg, Retinoid X Receptor alpha (RXRa) and Estrogen Related Receptor gamma (ERRg) – was studied by NMR. The structure of CBP in complex with any of these LBDs could not be solved, because of a strong signal attenuation of the residues implied in the interaction. Nevertheless, the aminoacids of CBP that interact with those 3 NRs could be mapped by this technique : they correspond to 2 discontinuous zones, delimited by the aminoacids (31 to 38) and (61 to 80), the latter containing the LxxLL motif. We also studied the interaction between CBP or SRCs fragments with lbd-PPARg and lbd-RXRa, in a comparative manner, by surface plasmon resonance and native electrophoresis. Our results show that CBP interacts preferentially with PPARg, whereas SRCs show a better affinity towards RXRa. We suggest that CBP might be directly recruited by PPARg/RXRa, which could play a role in the permissivity of this heterodimer
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Levy, Paul Blain. "Call-by-push-value." Thesis, Queen Mary, University of London, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369233.
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Roberts, Lindsey T. "Youth Views of Neighborhood Needs: A Photovoice Collaboration." Bowling Green State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1556617768952258.
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Pun, Jason. "The regulation of expression of the cbpA gene during Dictyostelium development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ39222.pdf.
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Chen, Wei 1969. "The mechanism of Cbp1 protein-dependent COBmRNA stability in yeast mitochondria." Diss., The University of Arizona, 1998. http://hdl.handle.net/10150/288848.
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It has been one hundred years since mitochondria were first observed and recorded by Altman in 1890, when they were named bioblasts. Ten years later, "mitochondrion", which means threadlike granule, started to be used. It is still an unanswered question where this organelle originated. More and more evidence and enthusiasm favor the hypothesis that mitochondria have evolved from engulfed prokaryotic symbionts (Martin and Muller, 1998). An opposing idea proposed that mitochondria just represent another kind of intracellular membrane system, like Golgi (Cavalier-Smith, 1987). Whichever is true, it is known today that mitochondria are well-defined and ubiquitous cellular structures compartmentalized by double membranes. They not only provide some of their own genetic information, but also are the site of cellular lipid synthesis and oxidative phosphorylation. Since mitochondria are such complex functional units, the study of mitochondrial biogenesis (a process to produce a respiratory competent organelle) is a combined issue of genetics, biochemistry and chemistry. It aims to answer questions regarding mitochondrial morphology, continuity, protein and phospholipid syntheses, protein transport, etc. This study is concentrated on a since regulatory step of a single mitochondrial gene in yeast, i.e. the stabilization of the cytochrome b (COB) mRNA, which requires the nuclear-encoded Cbp1 protein. The results of my study support that the nuclear-encoded Cbp1 protein stabilizes COB messages in two different ways: First, it processes the 5'-untranslated region (UTR); second, it is required after formation of the mature 5'-end of COB mRNA. Evidence is provided that Cbp1 physically interacts with a CCG element in the COB 5'-UTR, and the maintenance of this interaction is critical for COB mRNA accumulation. Suppressor analysis of COB 5'-UTR mutations identified factors in general mitochondrial mRNA turnover pathways. Thus, in addition to studying the mechanism of Cbp1-dependent COB mRNA stabilization, the further analysis of genes identified by mutation in this work may reveal previously uncharacterized components in the general pathways of yeast mitochondrial mRNA decay.
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Xu, Lan. "Integration of signal-induced transcriptional activation by CBP /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1998. http://wwwlib.umi.com/cr/ucsd/fullcit?p9911841.
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Sudwell, Mark Ian. "Chronic back pain : a narrative analysis." Thesis, University of Exeter, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.367457.
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Sabbir, Md Ahsan. "Corrosion Degradation Mechanism of CBPC Coating System for Highway Bridge Steel Components." FIU Digital Commons, 2017. http://digitalcommons.fiu.edu/etd/3179.
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Coatings are widely used to mitigate corrosion of structural steel in aggressive humid environments. However, the service life is often diminished in aggressive environments. Repair of coatings can be costly due to materials, labor and environmental controls. So, in search for novel coatings, Chemically Bonded Phosphate Ceramic (CBPC) coating was investigated for marine bridge application. The research on CBPC coating considered various exposure environments such as inland, beach, salt-fog, wet and alternate wet and dry exposure to identify the degradation mechanism. To assess the corrosion damage, the coating was evaluated by visual inspection, thickness, adhesion, microscopy and X-ray diffraction.
The CBPC coating degraded initially due to alternate wet and dry exposure. The unreacted coating constituent reacted further in moist environment to form magnesium phosphate hydrate and enhanced bulk coating porosity. That facilitated moisture to the coating substrate and formed apparent protective iron phosphate hydrate by interaction with steel substrate to the coating constituents. Passive-like conditions were observed in wet test of chloride-free solutions for the formation of hydration product of magnesium but that type of hydrate was not identified in chloride solution for the apparent high solubility. The resolved coating impedance parameters were introduced to characterize the bulk ceramic degradation. The solution resistance did show a decrease for all samples due to leaching of minerals from the bulk material. The resolved pore resistance did not show any distinct change, though there was an indication of bulk coating degradation by MIP. Water saturation level during exposure was also calculated from the resolved capacitance. An approach was proposed to transfer the pre-exponential term, Yo to coating capacitance, CC for ceramic coating. The estimated value of the coating capacitance from the developed technique indicated early saturation with water during exposure due to the porosity. So, the extent of CBPC coating permeability and degradation could not be resolved only by conventional analysis approaches. However, the formation of iron hydrogen phosphate hydrate and iron phosphate hydrate from reaction of unreacted coating constituents was thought to provide apparent enhanced corrosion protection but there is a probability of steel substrate corrosion in extended exposure in humid environment.
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Youssef, Ibrahim. "Contribution à la mise en place d'un système de génétique inverse pour le virus de la paralysie chronique de l'abaille." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4037/document.
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Le virus de la paralysie chronique de l’abeille (CBPV) est responsable d’une maladie infectieuse et contagieuse de l’abeille domestique. c'est un virus anisométrique et non enveloppé. Les premières études ont décrit son génome étant constitué de cinq segments d’ARN simple brin de polarité positive : deux ARN majoritaires et trois ARN minoritaires. Cependant, ces derniers n’ont pas été observés lors de récentes études. L’ARN 1 coderait pour les protéines non structurales et L’ARN 2 coderait pour deux protéines structurales.Les ARN totaux du CBPV sont infectieux chez l’abeille par inoculation intra-thoracique. Toutefois, les éléments génétiques essentiels à la réplication du virus n’étaient pas encore déterminés. Néanmoins, cette information est cruciale pour la mise en place du système de génétique inverse pour le CBPV afin de mieux caractériser ce virus. Lors de ce travail, nous avons montré le pouvoir infectieux des ARN majoritaires du CBPV. Ces résultats nous ont permis d'accomplir la première étape de la mise du système de génétique inverse pour le CBPV: le clonage des ARN majoritaires. Les résultats préliminaires montrent que les ARN transcrits in vitro à partir des plasmides recombinants sont répliqués in vivo après leur inoculation aux abeilles, mais ne conduisaient à aucun signe clinique de la maladie. Le système de génétique inverse du CBPV développé offrira la possibilité, par mutagenèse dirigée, de définir les fonctions des ORF et des protéines voire de permettre la production de protéines purifiées nécessaires à la production d’anticorps monoclonaux afin de développer un test rapide de diagnostic de la paralysie chroniqueChronic bee paralysis virus (CBPV) causes an infectious and contagious disease of adult honeybees. CBPV is an anisometric and non-enveloped virus. First studies described its genome as composed of five positive single-stranded RNAs: two major RNAs and three minor RNAs. However, these latest were not observed during recent studies. CBPV RNA 1 encodes for the non-structural proteins and RNA 2 encodes for two structural proteins. The total RNAs of CBPV are infectious by intra-thoracic inoculation of bees. However, the essential genetic elements for CBPV replication are still unknown. Besides, this information is crucial to develop a reverse genetic system in order to better characterize this virus.In this work, we showed the infectivity of CBPV major RNA. These results allowed us to accomplish the first step of the implementation of the reverse genetics system for CBPV: cloning of major RNA. Our preliminary results showed that RNA transcribed in vitro from recombinant plasmids replicated in vivo after inoculation to bees, but did not led to any clinical signs of the disease.The reverse genetics system developed for CBPV facilitate the study of CBPV genome, by site directed mutagenesis, the determination of its proteins functions. Moreover, it allows the expression of purified proteins necessary for production of monoclonal antibodies to develop a rapid diagnostic test for CBPV
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Kanko, Ivonne G. "Perceptions of Community-Based Participatory Research from Community and Academic Members." ScholarWorks, 2017. https://scholarworks.waldenu.edu/dissertations/3396.
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Community-based participatory research (CBPR) is an increasingly popular form of public health research. However, little is known about the application of CBPR and the levels of involvement for partners in specific phases of the partnership. This phenomenological study addressed the application of CBPR from the perspectives of 7 academic researchers and 6 community members experienced in CBPR. Arnstein's ladder of citizenship participation and the community coalition action theory provided the framework for the study. Semi-structured interviews addressed participants' levels of involvement in the CBPR process, as well as challenges, concerns, successes, and recommendations for improvement. Interview transcripts were analyzed by identifying recurrent themes relevant to the experience of being a CBPR partner. These themes were then used to develop descriptions of their experience. Results indicated that participants knew the term CBPR and had experienced it, but not all participants understood the depth of CBPR and how much bargaining power they could have for their community. Sustainability of partnerships and programs was a major concern. Ethical problems were also raised regarding the long-term commitment to projects and the need for CBPR partnership evaluation. Results may be used to strengthen awareness of the principles of CBPR to advance culturally tailored public health interventions.
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Kang, Hyun-Seo. "Structural foundation for transcriptional regulation by Ets1 and CBP." Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/28866.
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Using cell-based assays and biophysical measurements, we have defined the mechanism by which Ras/MAP kinase signaling enhances Ets1 regulated gene expression via phosphorylation-enhanced recruitment of the transcriptional co-activator CBP. As confirmed by ³¹P/¹³C-NMR experiments, the MAP kinase ERK2 phosphorylates Thr38 and Ser41 within the unstructured region of Ets1, immediately N- terminal to the PNT domain. The NMR-derived structure of residues 29-138 of Ets1 revealed that the PNT domain is composed of a core four-helix bundle (H2-H5), also known as the SAM fold, appended with two additional helices (H0-H1). Most importantly, helix H0 is only marginally stable as shown by various NMR methods, including chemical shift, amide hydrogen exchange, and ¹⁵N relaxation analyses.
Dual phosphorylation of Ets1 perturbs a "closed-open" conformational equilibrium of the PNT domain, displacing the dynamic helix H0 from the core bundle. These modifications increase the affinity of Ets1 for the TAZ1 (or CH1) domain of CBP by ~30 fold as measured with isothermal titration calorimetry (Kd ~ 60 to 2 μM). NMR-monitored titration experiments mapped the interaction surfaces of the TAZ1 domain and Ets1, the latter encompassing both the phosphoacceptors and PNT domain, also showing sensitivity to ionic strength. Charge complementarity of these surfaces indicates that electrostatic forces act in concert with the conformational equilibrium to mediate phosphorylation effects.
We conclude that the dynamic helical elements of Ets1, appended to a conserved structural core, constitute a "phospho-switch" to direct Ras/MAPK signaling to downstream changes in gene expression. This detailed structural and mechanistic information illustrates an evolutionary development within a gene family to increase the capacity for biological regulation.
We also discovered that the CBP TAZ1 domain associates intramolecularly with residues 28-82 in its N-terminal nuclear receptor interacting domain (NRID). NMR studies indicated that the NRID undergoes a coil-helix conformational transition upon binding the same interface on TAZ1 as recognized by many transcription factor partners. This led us to hypothesize that CBP is regulated by an auto-inhibitory mechanism. In support of this model, affinity of the hypoxia inducible factor HIF-1α for TAZ1 is reduced competitively by the presence of the NRID.
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Francis, Yitshak Itsik. "The role of CBP and p300 in Alzheimer's Disease." Thesis, University College London (University of London), 2008. http://discovery.ucl.ac.uk/1443955/.
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Studies of the mechanisms underlying memory formation have defined central roles for CRE-dependent gene expression, which is mediated by the transcription factor CREB and the coactivator CBP. CBP creates a bridge between CREB and the basal transcriptional machinery and acetylates histones, which induces chromosomal changes and results in loss of chromosomal repression. This allows successful transcription of the underlying genes needed for synthesis of proteins underlying memory formation. CBP has been linked to neurodegenerative diseases and cerebral CBP levels were shown to reduce in mice lacking functional presenilins (PSs), a class of enzymes that has been associated with Alzheimer's Disease (AD). In this thesis it is shown that WT PS1 stimulates the transcriptional activating ability of CBP and its close homolog p300, whereas an Alzheimer's disease- associated N terminal mutant of PS1 did not produce this effect. Interestingly, PS1 C terminal mutants produced a reduction in CBP transcriptional activating ability, compared to control levels. Additionally, we showed that wild type PS1 increases the endogenous CBP level. Moreover, an increase in CBP endogenous levels was noted when the cells were transfected with the -M146L N-terminal mutant of PSI. However, these levels were still significantly lower when compared to cells transfected with wild type PSI. We were also able to show that knockdown of endogenous PSI leads to a decrease in endogenous CBP levels and a decrease in CBP activity. Hence, PSI can affect both the level and the activity of CBP. In addition, the activation of CBP by WT PSI involves the PI 3-kinase, p38 MAP kinase and p42/p44 MAP kinase pathways and targets primarily the C terminus of CBP. It is also shown that the effect of wild-type PSI is dependent on the histone acetyltransferase activity (HAT) of CBP. Moreover, it was demonstrated that WT PSI, but not its M146L mutant, could increase the promoter activity of c-fos, a CBP HAT dependent target gene. Additionally, we showed that application of the histone deacetylase inhibitor, TSA, rescued the long-term potentiation and long-term memory defects shown by APP/PS1 mutant mice. Moreover, it was shown that the acetylation level of histone H4 in APP/PS1 mice is lower than that of WT littermates and that TSA injection restores the acetylation of these histones. This is the first study to identify AD as a disease of epigenetic etiology and suggests that enhancing histone acetylation may have potential for the treatment of AD.
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Gusterson, Rosalind Jane. "The role of CBP and p300 in cardiac hypertrophy." Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.399576.
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Dari, Tahani Hisham. "Development and Validation of Community-Based Participatory Research (CBPR) Competencies: A Delphi study." University of Toledo / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1497847022189756.
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Alvarez, David 1971. "The involvement of CBP/14-3-3 in DNA replication /." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=82819.
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Initiation of DNA replication is a cellular process whose regulation is not well understood yet. It certainly depends on cis-acting elements, or origins of DNA replication sequences, and trans-acting factors, or initiator proteins. Here, we have characterized the Cruciform Binding Protein (CBP) as an origin binding protein and its role in initiation of DNA replication.CBP was previously shown to contain the β, ɣ, ε, and ζ isoforms of the 14-3-3 family, which is composed of seven mammalian isoforms (β, ɣ, ε, η, σ, τ, and ζ) that can form homo- and heterodimers, and plays a variety of roles in different cellular processes. In this thesis, I showed by Western blot analysis with anti-14-3-3σ antibody, which partially interfered with the CBP-cruciform DNA complex formation, that the isolated CBP-cruciform DNA complex contained also the σ isoform. The same antibody reduced the in vitro DNA replication efficiency of HeLa cell total extracts, in an assay that used p186, a plasmid bearing the 186-bp minimal origin of ors8, as template DNA. Similarly, I found that antibodies against 14-3-3 isoforms β, ɣ, ε, and ζ also interfered with the CBP-cruciform DNA complex formation, and reduced the in vitro p186 replication efficiency of HeLa cell total extracts. The five isoforms of 14-3-3 (β, ɣ, ε, σ, and ζ) were found to associate with the monkey cell (CV-1) origins of DNA replication ors8 and ors12 in a cell cycle-dependent manner, the association being higher at the G1/S phase. Furthermore, we found that 14-3-3 yeast homologues, Bmh1p and Bmh2p, were able to bind cruciform DNA in vitro, and to associate in vivo with the autonomous replication sequence 307 (ARS307) in a cell cycle-dependent manner, again the association being higher at G1/S. Finally, I showed that recombinant 14-3-3ζ, tagged with maltose-binding protein (r14-3-3ζ-MBP), could only bind cruciform DNA after pre-incubation with a CBP-enriched HeLa cell extract (FTH), in which it heterodimerized with endogenous 14-3-3 isoforms β and ε. Addition of r14-3-3ζ-MBP to HeLa cell total extracts increased the in vitro replication of p186, suggesting that increased CBP activity could lead to multiple rounds of initiation of DNA replication.
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Tessarolo, Diane. "Cytoskeletal localization and function of calcium-binding protein 1 (CBP1) during Dictyostelium discoideum development." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/MQ59208.pdf.
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Gouveia, Ayden. "The Atypical Protein Kinase C - Creb Binding Protein Pathway Regulates Post-Stroke Neurovascular Remodeling and Functional Recovery." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/35674.
Full textAbstract:
Ischemic stroke related brain damage causes loss of multiple cell types, including neural and vascular cells. The extent of post-stroke neurogenesis and angiogenesis predicts the level of functional regeneration/recovery after stroke. In this regard, my thesis was focused on defining the molecular process that modulates post-stroke functional recovery by co-ordinating post-stroke neurovascular remodeling. Since stroke-related brain damage releases enriched local microenvironmental cues, I examined the role of a signaling-induced epigenetic pathway, an atypical protein kinase C (aPKC)-mediated phosphorylation of CREB Binding Protein (CBP), in regulating post-stroke neurovascular remodeling and functional recovery. This pathway has previously been shown to be activated by metformin, an adenosine monophosphate kinase (AMPK) activator, to promote the differentiation of neural precursors in the developing and adult brain. Here, I first developed a murine focal cortical ischemic stroke model with persistent motor function deficits by combined intra-cortical injections of endothelin-1 (ET-1) and L-NAME into the sensorimotor cortex. Second, I applied the ET-1/L-Name-induced focal cortical stroke model in a knock-in mouse CBPS436A where the aPKC-CBP pathway is deficient, and showed that the aPKC-CBP pathway is involved in post-stroke functional recovery by coordinating neurovascular remodeling. Specifically, CBPS436A-KI mice displayed reduced motor recovery, correlated with reduced vascular remodeling and impaired post-stroke angiogenesis. Intriguingly, I also observed that CBPS436A-KI mice showed a reduction in the population of stroke-induced newborn pericytes but an increase in the population of perivascularly-derived neural precursors, implying that the aPKC-CBP pathway may be involved in the process that reprograms pericytes into neural precursors. Together, this study elucidates the novel role of the aPKC-CBP pathway in modulating neurovascular remodeling and functional recovery following focal ischemic cortical stroke.
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Grier, Karissa Niphore. "Feasibility of an Experiential Community Garden and Nutrition Program for Youth Living in Public Housing:Exploring Outcomes from Youth, Parents and Site Leaders." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/48901.
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Background: Community gardens have existed in America since the late 1800s and have served multiple purposes from food subsidies to neighborhood beautification. The use of community gardens has grown in popularity and has been recommended as a way to encourage healthy eating habits in youth. Though the health benefits of having a diet high in fruits and vegetables is well known, youth in the United States do not meet recommendations for fruit and vegetable intake. Under-consumption of fruits and vegetables is problematic in youth, as eating habits are established in childhood. Community gardens have been successfully used to improve access, self-efficacy, preference, and consumption of fruits and vegetables. However, few published community garden studies have focused on low socioeconomic youth. The Dan River Partnership for a Healthy Community (DRPHC) was developed according to community-based participatory research (CBPR) principles. With a mission to reduce obesity using healthy lifestyle initiatives, community gardens are an evolving DRPHC initiative.
Objective: To evaluate the feasibility (i.e., demand, acceptability, implementation, and limited-effectiveness testing) of a 10-week experiential theory-based gardening and nutrition education program targeting youth living in two public housing sites in the Dan River Region.
Methods: Using pre- and post-program questionnaires/interviews, demand and acceptability were measured among youth, parents and site leaders. Implementation was measures via field notes and attendance. Limited-effectiveness was measured among youth using a pre-post design. Three researchers independently coded the qualitative transcripts, met to resolve disagreements, and built consensus through discussion of the codes. Similarly, field notes were reviewed and evaluated for reoccurring themes regarding barriers, facilitators, and other observations. For the quantitative measures, descriptive statistics were used to summarize the variables and Cronbach's alphas used to assess the reliability of each scale at baseline. Overall effects were tested with repeated measures ANOVA. An intent-to-treat analysis using the last observation carried forward method was used. A critical value of .05 was used for significance testing. A standard equation for reporting effect sizes on a single-group, pre-post study design is also reported.
Results: Program enrollment included 43 youth, primarily African American. The positive demand and acceptability findings indicate the potential of the program to be used and suitable for the youth, parents, and site leaders. Field notes revealed numerous implementation facilitators and barriers. Youth weekly attendance averaged 4.6 of 10 sessions. Significant improvements (p<0.05) were found for some (e.g., FV asking self-efficacy, overall gardening knowledge, knowledge of MyPlate recommendations), but not all limited-effectiveness measures (e.g., willingness to try FV, FV eating self-efficacy).
Study Implications: This study addresses recommendations for utilizing CBPR in community garden efforts and builds on community identified research priorities of the DRPHC. Results demonstrate the feasibility of a gardening and nutrition program targeting youth in public housing. Lessons learned are being used to adapt and strengthen the program for future efforts targeting FV behaviors. Findings will be shared with local community stakeholders and used to adapt and strengthen the program for future efforts in the Dan River Region targeting of fruit and vegetable behaviors.Master of Science
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Soremekun, Mishael. "Readmission in psychosis and in CBTp : associations with patient education level and belief flexibility status." Thesis, Royal Holloway, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604562.
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Background and objectives Previous studies have shown that Cognitive Behavioural Therapy for psychosis (CBTp) does not reduce readmission rates. This could be due to particular patient characteristics. This study sought to assess whether patients' education level and belief flexibility status were associated with readmission following CBTp treatment. The association between other psycho-social factors and readmission was also explored. Method Using the South London and Maudsely NHS Trust case register, 3025 adult patients with an F20-F29 ICD-1O diagnosis, discharged from inpatient care to the community during 2008-2009 were identified. They were categorised on the basis of their level of education, belief flexibility status and other psycho-social variables and followed-up until December 2011 , to ascertain their time to readmission. Results Cox proportional regression analyses showed that those with a G.C.S.E. level education were significantly less likely to readmit when compared with those with no qualifications. A trend for lower readmission was also observed in the A' level and above group. There was no evidence of an association between belief flexibility and readmission in patients who had CBTp treatment (N=469). A trend for a lower rate of readmission was observed for those with a G.C.S.E. level education in the CBTp sample. Other psycho-social factors were strongly associated with readmission for all patients. Conclusion These findings suggest that some psycho-social factors are important for readmission in psychosis, but not belief flexibility. Structural changes to mental health service provision in the UK are indicated to tackle this client group who experience high levels of social adversity. Modifications to CaTp provision to increase access to a full course ofCBTp are also needed. Future studies with larger CaTp samples that explore the relationship between belief flexibility and readmission and the impact of structural-level interventions could help further our understanding in this area.
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Jeronymo, Vanice. "Conflitos, impasses e limites na preservação do patrimônio industrial paulista: o caso da Perus (CBCPP)." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/102/102132/tde-11042017-113516/.
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Trata dos critérios utilizados para efetivar o tombamento de remanescentes de um conjunto industrial: a Companhia Brasileira de Cimento Portland Perus - CBCPP. Procura-se analisar como foram acatadas as solicitações de tombamento deste complexo nas três esferas públicas municipal, estadual e federal e identificar os conflitos que emergiram ao longo do desenvolvimento de tais ações e os efeitos destes sobre a materialidade do conjunto. Busca-se verificar os conceitos e procedimentos metodológicos utilizados no trato da questão pelos respectivos órgãos de preservação e analisar como foram considerados valores, condição de integridade e autenticidade dos elementos do conjunto ao incluí-los, ou não, na delimitação dos tombamentos, juntamente com os reflexos em suas condições físicas. Constituem como objetos de pesquisa as iniciativas para preservação da Estrada de Ferro Perus-Pirapora EFPP - e dos polos de produção da empresa ligados às atividades extrativistas e à produção de cimento, juntamente com os assentamentos operários edificados no bairro de Perus, em São Paulo e nos bairros de Água Fria e Gato Preto, em Cajamar. Tem como objetivo principal analisar em que medida os conflitos e tensões que emergiram durante tais processos influenciaram nos limites alcançados pelos tombamentos e contribuíram com a preservação, ou com a destruição, descaracterização e mutilação dos bens. A atual situação do conjunto, imerso em disputas pelo direito de fruição, ou vulnerável a intervenções em suas edificações, justificam a pertinência do estudo em questão. A investigação foi baseada em pesquisa bibliográfica sobre o tema abordado, processos de tombamento e levantamentos em campo.It deals with the criteria used to effect the tipping of remnants of an industrial complex: Companhia Brasileira de Cimento Portland Perus - CBCPP. It seeks to analyze how the requests for the registration of this complex in the three public spheres - municipal, state and federal - have been complied with and to identify the conflicts that emerged during the development of such actions and their effects on the materiality of the set. It seeks to verify the concepts and methodological procedures used in the treatment of the issue by the respective preservation agencies and to analyze how they were considered values, condition of integrity and authenticity of the elements of the set when including them or not in the delimitation of the recordings, together with the reflexes in their physical conditions. The initiatives for the preservation of the Perus-Pirapora Railway - EFPP - and the company\'s production centers linked to extractive activities and cement production, together with the workers\' settlements built in the Perus district of São Paulo and in the neighborhoods of Água Fria and Gato Preto, in Cajamar. Its main objective is to analyze to what extent the conflicts and tensions that emerged during such processes influenced the limits reached by the takedowns and contributed to the preservation or destruction, de-characterization and mutilation of goods. The current situation of the whole, immersed in disputes for the right of fruition, or vulnerable to interventions in its buildings, justify the relevance of the study in question. The research was based on bibliographical research on the topic addressed, processes of tipping and surveys in the field.
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Lopes, Tiago Deiveson Pereira. "Potencial antidermatofítico de Mo-CBP4, uma proteína ligante à quitina de sementes de Moringa oleifera." reponame:Repositório Institucional da UFC, 2016. http://www.repositorio.ufc.br/handle/riufc/18906.
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LOPES, Tiago Deiveson Pereira. Potencial antidermatofítico de Mo-CBP4, uma proteína ligante à quitina de sementes de Moringa oleifera. 2016. 104 f. Dissertação (Mestrado em Bioquímica)-Centro de Ciências, Universidade Federal do Ceará, Fortaleza, 2016.Submitted by José Jairo Viana de Sousa (jairo@ufc.br) on 2016-08-03T20:07:36Z No. of bitstreams: 1 2016_dis_tdplopes.pdf: 2164027 bytes, checksum: f658448ab9dc0c04c309f8347b4b887d (MD5)
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Dermatophytosis constitute an important public health problem, affecting about 25% of world population. Several drugs are available for the dermatophytosis treatment, but they cause many adverse effects, including severe toxicity, drug interactions, low efficacy and resistance. Thus, there is a need for the development of new drugs with improved efficacy and safety. Medicinal plants are a valuable source of natural products that can act as drugs, being an alternative to conventional treatments. Moringa oleifera Lamarck, a plant native from Northeast of India, is widely used for its nutritional, therapeutic and water purification properties. Thus, this study aimed to evaluate the antidermatophytic potential of Mo-CBP4, a chitin-binding protein purified from M. oleifera seeds. By in vitro assays, Mo-CBP4 showed inhibitory activity against the fungus Trichophyton mentagrophytes, with a MIC50 of 500 µg/mL. In contrast, Mo-CBP4 did not inhibit the fungus T. rubrum, even at a higher concentration (1000 µg/mL). Mo-CBP4 (500 μg/mL) was able to inhibit the conidia germination of T. mentagrophytes, but not the mycelial growth. In relation to the mode of action, the antifungal activity of Mo-CBP4 does not seem to involve the carbohydrate interaction site since the protein remained active even when incubated with 0.15 M N-acetyl-D-glucosamine. The antifungal activity of Mo-CBP4 appears to result from the increased permeability of the conidia cell membrane and induction of oxidative stress within the cell, cause by this protein. Mo-CBP4 also showed antifungal activity against T. mentagrophytes by in vivo assays. In dermatophytosis model using albino Swiss female mice the hydrogel containing Mo-CBP4 (5 and 10 mg/g) was effective, reducing the lesion severity and shortening the infection period. The findings indicate that Mo-CBP4 has potential for development of a novel antifungal drug for clinical treatment of dermatophytosis caused by the fungus T. mentagrophytes.
As dermatofitoses são consideradas um problema de saúde pública, afetando cerca de 25% da população mundial. Vários medicamentos estão disponíveis no mercado para tratar dermatofitoses, porém essas drogas trazem muitos efeitos adversos, incluindo elevada toxicidade, interações medicamentosas, pouca eficácia e desenvolvimento de resistência. Assim, a busca por novas drogas mais seguras e eficazes é imperativa. As plantas medicinais constituem uma valiosa fonte de produtos naturais capazes de atuar como fármacos, caracterizando-se como uma alternativa aos tratamentos convencionais. Moringa oleifera Lamarck, uma planta originária do Norte da Índia, é bastante utilizada por suas propriedades nutricionais, purificadora de água e terapêuticas. Diante disso, esse trabalho objetivou avaliar o potencial antidermatofítico de Mo-CBP4, uma proteína ligante à quitina, purificada de sementes de M. oleifera. Através de ensaios in vitro, Mo-CBP4 apresentou atividade inibitória frente ao fungo Trichophyton mentagrophytes, apresentando um CIM50 de 500 μg/mL. Contrariamente, Mo-CBP4 não inibiu o fungo T. rubrum, mesmo em uma concentração mais elevada (1000 μg/mL). Mo-CBP4 (500 μg/mL) foi capaz de inibir a germinação de conídios de T. mentagrophytes, mas não o crescimento micelial. Em relação ao modo de ação, a atividade antifúngica de Mo-CBP4 não parece envolver o sítio de interação a carboidrato desde que mesmo incubada com N-acetil-D-glucosamina 0,15 M permaneceu ativa. A atividade antifúngica de Mo-CBP4 parece resultar do aumento da permeabilidade da membrana dos conídios e indução de estresse oxidativo no interior das células, causado pela proteína. Atividade antifúngica de Mo-CBP4 contra T. mentagrophytes foi também verificada em ensaio in vivo. Em modelo de dermatofitose animal, utilizando camundongos albinos Swiss fêmeas, o hidrogel contendo Mo-CBP4 (5 e 10 mg/g) se mostrou eficaz no tratamento da infecção causada por T. mentagrophytes, diminuindo a gravidade das lesões e abreviando o tempo de infecção. Os dados obtidos indicam que Mo-CBP4 tem potencial para o desenvolvimento de uma nova droga antifúngica a ser utilizada no tratamento de dermatofitose causada por T. mentagrophytes.
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Ramírez, Sandra. "Role du coactivateur cbp dans l activite du sre de c-fos." Paris 12, 1999. http://www.theses.fr/1999PA120092.
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La proteine cbp, connue pour etre un coactivateur de plusieurs facteurs de transcription dependants du signal est un integrateur des differents voies de signalisation et elle est aussi impliquee dans la regulation de la transcription du proto-oncogene c-fos. Nous avons partie de la hypothese que cbp cooperer avec srf pour la l'activation transcriptionnelle en reponse au serum l'element sre. Dans une premiere etude faite dans la lignee cellulaire f9 nous avons montre que cbp stimule de facon dose dependante l'activite du gene rapporteur luciferase sous le controle de l'element sre du promoteur de c-fos. La partie amino-terminale de la proteine cbp est suffisante pour activer cette transcription. De plus nos resultats montrent que l'activation est independant du motif reconnu par les proteines ets, la boite ets dans sre. Par ailleurs, nous avons montre que la proteine cbp forme un complexe in vivo avec la proteine srf dans des cellules u20s. Tous ces resultats montrent que cbp joue un role de coactivateur de la transcription du facteur de transcription srf dans l'activation du proto-oncogene c-fos via le sre. Un de mecanismes par lesquels cbp peut cooperer dans l'activation de la transcription est en faisant le pont entre les facteurs de transcription et la machinerie basale de transcription. Il est connu que cbp interagit avec certaines facteurs generaux de la transcription, tels que tbp et tfiib. Un deuxieme mecanisme pourrait etre la modulation de la structure chromatinienne grace a l'activite hat intrinseque de cbp ou a une activite hat recrute par elle meme ou de facon independant de cbp. Nous avons montre que cbp est phosphorylee pendant la transition g1/s du cycle cellulaire et que pendant cette meme periode l'activite hat de cbp est maximale. Nous avons egalement demontre que cbp peut etre phosphorylee, dans sa region carboxyterminale, en dehors de son domaine a activite hat, par les mapks et particulierement par erk2. Avec l'aide du test hat mis au point par mr. Ait-si-ali dans notre laboratoire, nous avons trouve que cette phosphorylation stimule de facon significative l'activite hat de la proteine cbp. Ces donnees permettent de mieux comprendre le role important de la proteine cbp dans le controle de la transcription et son implication dans le bon deroulement de la proliferation et de la differentiation cellulaires.
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Menezes, Sean Christopher. "Examining the effect of CBP on the E2A-PBX1 and HOXB4 interaction." Thesis, Kingston, Ont. : [s.n.], 2008. http://hdl.handle.net/1974/1534.
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Farrell, Cynthia S. "Chronic Pain Management in a Reservation Border Town." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/195767.
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Pain is a growing national public health problem that contributes to spiraling health care costs and significant societal burden in the United States. It is the most common reason for seeking health care services, and is the leading cause of disability (CDC, 2008). Inadequately treated pain has profound social, psychological, economic, and physiological consequences for patients, their families, and society (American Pain Society, 2009).A community-based participatory research (CBPR) approach was used for this project to develop a knowledge base about issues associated with chronic pain and its treatment among Native American people in Winslow, AZ. Mixed methods (qualitative and quantitative) were used to gain insight into the local factors that contribute to the self-management and treatment of chronic pain.The results of a provider survey indicated that there are negative psychological traits toward patients with chronic pain such as authoritarianism, intolerance of ambiguity, reliance on technology, and locus of control which are factors that are known to negatively influence pain care (Weinstein et al, 2000). Lack of knowledge regarding pain and pain management along with perceptions and fears related to drug regulatory agencies were additional factors that were found, constituting additional barriers. Patient participants were generally dissatisfied with the pain care practices at Winslow Indian Health. Patient reported treatment goals that included relief of pain, improved quality of life, the ability to return to work, the ability to perform household chores, and the ability to participate in more physical leisure activities.This results of this practice inquiry indicate there is a disconnect between patient and provider views and expectations around pain treatment and the need for further studies to determine the best ways to address chronic pain at the local level. The development of a pain management program is recommended to address the unmet needs of patients with chronic pain. Education in pain management is recommended for healthcare providers, including information regarding the benefits of non-pharmacologic therapies for pain management. The practice inquiry also supports the need for new policies at the local, tribal, and national levels to address pain as a growing public health issue.
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Masibag, Angelique Noelline. "Characterization of a New Peptidomimetic Compound Modulating Sam68 Functions in Human Colon Cancer Stem Cells." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42301.
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Background:
Conventional chemotherapeutics target bulk tumour cells and generally leave cancer stem cell (CSC) populations unaffected. Recent literature characterized the presence and the role of CSC in several types of solid tumors, including colorectal cancer. Colorectal CSCs (CCSCs) display enhanced WNT/β-catenin pathway activity, sustaining self-renewal and tumor-initiating capacity. Thus, CCSCs are crucial for tumour recurrence and metastasis. As one of the main contributors to sustained self-renewal activity in CCSCs, enhanced formation of β-catenin/CBP complex is
fostering transactivation of canonical WNT target genes such as c-myc. However, maintenance of healthy intestinal stem cells also dependents on the canonical WNT pathway. Thus, selective targeting CCSCs while sparring normal intestinal cells is still a significant challenge. Interestingly, Sam68 is a key mediator of the interaction between β-catenin and CBP. It has been reported as a “druggable” target to selectively disrupt β-catenin/CBP in CSCs. Indeed, CWP232228 successfully targets CSCs in AML by facilitating Sam68/CBP complex formation, and consequently lowering the abundance of β-catenin/CBP complexes. CWP232228 was clinically tested on
multiple human cancers. Unfortunately, such clinical trials were halted due to unknown causes, and limited information was released on clinical safety and benefits. Consequently, developing more potent pharmacological modulators of Sam68/CBP complex formation is still highly relevant to eradicate CCSCs. Here we describe the discovery and characterization of a new CWP analog, known as YB-0158, which displays enhanced potency and neoplastic selectivity against CCSC. Methods and Results:
Following the confirmation that ICG/CWP class of compounds bind to Sam68 in CSCs, I used in silico docking methods to screen for CWP analogs having high predicted affinity for Sam68 Cterminal proline-rich domain. Using high content imaging techniques, I confirmed our top candidate (YB-0158) as more potent vs. CWP parent molecule to compromise cell growth, to induce loss of pluripotency, and to increase Sam68 nuclear localization in a surrogate model of human CSCs. YB-0158 also displayed enhanced selective toxicity in colorectal cancer models vs. normal intestinal epithelium progenitor cells. Moreover, I confirmed that YB-0158 exert negative impact on cancer cell growth by inducing apoptosis and reducing proliferation. Lentiviral-based knockdowns explicitly displayed decrease in drug effectivity in the absence of Sam68, reinforcing the essential role of Sam68 mediating ICG-001/CWP response in CSCs. I demonstrated that Sam68 expression is enriched in tumor-initiating cell fractions derived from primary colorectal tumor tissues vs. bulk heterogeneous tumor organoids. Therefore, YB-0158 showed striking efficacy at supressing tumor-initiation activity in a patient-based serial organoid formation assay. Finally, YB-0158 eradicated CSCs activity in vivo as demonstrated by a syngeneic mouse-to-mouse serial transplantation assay.
Conclusion:
Overall, YB-0158 is a novel analog of CWP232228 with superior potency to target CCSCs activity through facilitation of Sam68 nuclear localization, thus reducing the interaction frequency between CBP and β-catenin.
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Smyth, Amy Marie. "An investigation into the initial validity of the Canterbury behaviour screening protocol (CBSP): a pilot study." Thesis, University of Canterbury. Health Sciences, 2006. http://hdl.handle.net/10092/1406.
Full textAbstract:
This study was a pilot investigation of the initial validity of a newly developed behaviour-screening instrument for early intervention service providers. Group Special Education, Early Intervention (GSE/EI) (2005) adapted the Canterbury Behaviour Screening Protocol (CBSP) from a widely used behaviour-screening instrument the Early Screening Project. The CBSP consisted of 49 items in 2 checklists. GSE/EI identified 10 early childhood centres with a total roll of 712 to participate in the study. Staff were asked to categorise children's problem behaviours as either withdrawn/isolated or aggressive/oppositional, using profiles provided. Next, they were asked to nominate 2 children in each category, and an additional 2 children in either category, and to rank them from most concerning to least concerning. Centres identified 25 children in the withdrawn/isolated category, and 28 children in the aggressive/oppositional category. Staff completed checklists for children with parent/carer consent, which were scored according to preset protocols. Scores on the CBSP were assigned risk values ranging from "extreme" to "no risk". The estimated prevalence of "high" to "extreme" behaviour problems was 7.2% based on CBSP protocols and teacher nominations. The level of agreement between teacher rank and CBSP score was 79%, and this determined the initial specificity. Next, independent observations of the behaviour of the nominated children were conducted during free play periods at the centres by an observer blind to the children's nominated category, teacher ranking or checklist score. Risk levels were assigned based on the observation scores, using a cut-off value of 37% time spent in problem behaviour for girls and 40% for boys. There was agreement in terms of teacher rank and observation scores, (categorised into either "no risk" and "at/high/extreme risk) for 65% for children in the withdrawn/isolated category, and 75% for children in the aggressive/oppositional category. The level of agreement between the CBSP score and the observations (categorised into either "no risk" or "at/high/extreme" risk) was 40% for children in the withdrawn/isolated category, and 46% for children in the aggressive/oppositional category. Using the cut-off values, a prevalence estimate for high risk or extreme risk for behaviour disorders, based on independent observation of children, was 3.2%. Centre staff completing a feedback form determined the social validity of the CBSP. Although responses were generally favourable, a number of suggestions were also made to improve the procedure. Despite limitations in the design of the draft, the CBSP shows promise for a first step in a screening procedure designed to screen New Zealand early childhood centres for children who may be at risk for developing behaviour and/or social emotional problems. The independent observation may also be useful as a second step, prior to extensive eligibility assessment. A number of suggestions were made for future drafts such as addressing the limitations specified, conducting the CBSP with a greater number of children, and determining the concurrent validity, and test-retest reliability.
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Dharamsi, Akil G. "Studies on the function of Calcium Binding Protein 1 (CBP1) during the development of Dictyostelium discoideum." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ27345.pdf.
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Cartwright, Macey D. "Addressing Math Competence in Low-SES Children using a CBPR Approach:The Role of Personalized Math Practice." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin152457048814441.
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Liu, Yuxiang. "Characterization and functional analyses of the CRT1-CBP1-NUC1 gene cluster in the yeast Saccharomyces cerevisiae." Diss., The University of Arizona, 1991. http://hdl.handle.net/10150/185623.
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Two yeast nuclear genes (NUC1 and CRT1) that flank CBP1 were studied. NUC1 is located 230 bp downstream of CBP1 and encodes a major mitochondrial nuclease. In strains which carry double stranded RNA (dsRNA) virus L-A, disruption of NUC1 causes a dramatic increase in the level of L-A dsRNA genome and its product, the viruslike particle coat protein. This phenotype is similar to that observed in a strain with a mutation in the nuclear gene encoding the most abundant outer mitochondrial membrane protein, porin. The disruption of NUC1 does not affect the level of porin. Mutations in NUC1 are recessive with respect to virus overexpression and the overexpression phenotype can be suppressed by the presence of M type dsRNA. In both NUC1 and nuc1 strains, virus abundance is increased by growing cells in a medium containing a nonfermentable carbon source, an effect independent of the increase in coat protein and viral genome due to nuc1 mutations or to the absence of M. Since mutations in NUC1 affect the abundance of L-A but not M, NUC1 defines a new family of nuclear genes involved in dsRNA metabolism. CRT1 is located 270 bp upstream of CBP1 and encodes a function related to yeast respiration. CRT1 produces two RNA species which are 0.8 and 0.9 kb. The longer transcripts are initiated upstream of the open reading frame and are expressed constitutively, while the shorter transcripts are initiated within the open reading frame and are induced 8 to 10-fold upon carbon source derepression. Sequence analysis revealed that the open reading frame could encode a basic protein with a molecular weight of 30.7 kDa. The deduced amino acid sequence indicates that the CRT1 protein has putative zinc finger, leucine zipper, and acidic blob domains, which are typical of transcriptional regulatory proteins. A complete deletion of CRT1 from the genome has no apparent phenotype. Thus, CRT1 is not an essential yeast gene. A gene (CRT2) that duplicates the function of CRT1 was identified in a synthetic lethal/respiratory deficiency screen. The function of either CRT1 or CRT2 is sufficient to support respiration in yeast. Therefore, CRT1 may encode a regulatory factor involved in the expression of genes encoding respiratory functions.
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Walia, Mannu. "La méthylation de CBP détermine des sites de liaison distincts au niveau de la chromatine pour le récepteur nucléaire à l'estradiol." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ006.
Full textAbstract:
L’oestradiol est l’une des hormones sécrétées par les ovaires. Non seulement impliquée dans le développement des organes sexuels chez les femmes, cette hormone aurait également un rôle important dans la carcinogénèse. En effet, l’oestradiol agit comme facteur de croissance dans le cancer, et c’est pourquoi la thérapie anti-hormone apparaît efficace dans le traitement du cancer du sein. Dans ce projet, nous avons étudié comment une seule molécule pouvait être aussi polyvalente, en modifiant certains cofacteurs altérant ainsi l’expression de certains gènes. L'Œstradiol agit sur l’ADN en recrutant le récepteur aux œstrogènes via les éléments hormonaux-sensibles. La liaison des œstrogènes sur leurs récepteurs induit un changement dans leur conformation et déclenche le recrutement de co-activateurs. Ces co-activateurs, tels CARM1 et CBP qui sont des enzymes épigénétiques majeures, sont recrutés par les gènes cibles des œstrogènes. Bien que ce mécanisme soit connu, la signification fonctionnelle du recrutement d’HAT et d’une méthyltransférase restait toujours non élucidée. Au cours de ma thèse, j’ai démontré que la protéine CBP est spécifiquement et exclusivement méthylée par CARM1 in vivo et qu’il existe plusieurs formes de méthyl-CBP qui recrutent et régulent différents gènes clefs dans la voie de signalisation des œstrogènes. Pour la première fois, nous avons défini un « code pour les modifications des co-activateurs », qui est impliqué dans la réponse endocrinienne et pourrait être dérégulé dans la progression tumorale du cancer du sein. Ces résultats mettent en évidence la régulation croisée entre les deux enzymes épigénétiques CARM1 et CBP comme une réponse essentielle aux œstrogènes et révèlent pour la première fois le mécanisme singulier par lequel les gènes cibles des œstrogènes sont régulésEstradiol is one of the hormones secreted by the ovaries. Not only involved in sexual development of women, this hormone would also have a significant role in carcinogenesis. Indeed estradiol acts as growth factor in cancer and this is why anti-hormone therapy is effective in breast cancer. In this project we investigated how a single molecule can be so diverse with respect to modulating certain cofactors and thus altering gene expression. Estradiol acts on DNA by recruiting the estrogen receptor on the hormone responsive elements. The binding of estrogen to its receptor induces a conformation change on the receptor which mediates the recruitment of co-activators. Coactivators such as CARM1 and CBP which are major epigenetic enzymes are recruited on estrogen target genes. Although this mechanism was known, the functional significance of recruiting a HAT and a methyltrasferase was still impending. In my thesis, I have shown that CBP is specifically and exclusively methylated by CARM1 in vivo and that there are several combinations of methyl CBP species which recruit and regulate distinct gene hubs in estrogen signaling. For the first time we define a “code for coactivator modifications”, which is involved in endocrine response and could be deregulated in tumor progression in breast cancer. These results identify the cross regulation between the two epigenetic enzymes CARM1 and CBP as a pivotal response to estrogen and reveal for the first time a distinct mechanism by which estrogen target genes are regulated
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Chevin, Aurore. "Le virus de la paralysie chronique de l'abeille : contribution à l'étude de la caractérisation de protéines virales." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4734/document.
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Le virus de la paralysie chronique de l'abeille (Chronic bee paralysis virus, CBPV) est l'agent étiologique d'une maladie infectieuse et contagieuse des abeilles adultes (Apis mellifera L.), appelée la paralysie chronique. Le CBPV est un virus à ARN simple brin positif qui contient 2 fragments d'ARN majoritaires. L'ARN 1 (3674 nt) et l'ARN 2 (2305 nt) codent respectivement 3 et 4 cadres ouverts de lecture (ORF). La séquence d'acides aminés de l'ORF 3 de l'ARN 1 partage des similitudes avec l'ARN polymérase ARN dépendante (RdRp) des virus des familles Nodaviridae et Tombusviridae. Par analogie avec ces familles virales, il a été suggéré que l'ARN 1 coderait les protéines non-structurales tandis que l'ARN 2 coderait les protéines structurales. Cependant, la réalité de ces protéines virales doit être démontrée expérimentalement afin d'étudier leurs fonctions, de mieux décrire ce virus et sa position taxonomique ainsi que d'améliorer les outils de diagnostic. Dans ce but, différentes approches expérimentales ont été utilisées. Une comparaison des protéomes d'hémolymphe d'abeilles non-infectées et infectées par le CBPV a été effectuée. Les protéines différentiellement exprimées ont été identifiées par empreinte peptidique massique (peptide mass fingerprint, PMF). Cette étude a permis d'identifier des protéines de l'abeille dont certaines contribueraient à une réponse immunitaire antivirale, mais aucune protéine virale n'a été identifiée par cette approche. Les ARN extraits du CBPV ont été utilisés dans des expériences de traduction in vitro. Malgré plusieurs essais réalisés en faisant varier les conditions expérimentales, cette approche s'est révélée infructueuseChronic bee paralysis virus (CBPV) is the etiological agent that causes an infectious and contagious disease in adult bees (Apis mellifera L.), called chronic paralysis. CBPV is a positive single-stranded fragmented RNA virus which contains 2 major viral RNA fragments. RNA 1 (3674 nt) and RNA 2 (2305 nt) encode 3 and 4 putative open reading frames (ORFs), respectively. The amino acid sequence of ORF 3 on RNA 1 shares similarities with the RNA-dependent RNA polymerase (RdRp) of virus families Nodaviridae and Tombusviridae. By analogy with these viral families, it has been suggested that RNA 1 encodes non-structural proteins and RNA 2 encodes structural proteins. However, the reality of viral proteins needs to be experimentally demonstrated in order to study theirs functions, to describe CBPV biology and its taxonomic position and to improve diagnostic tools. With this aim, different experimental strategies have been used.A comparison of hemolymph proteomes between uninfected bees and bees infected with CBPV was performed. Differentially expressed proteins have been identified using peptide mass fingerprint method (PMF). This study allowed only identifying proteins of bees which could contribute to an antiviral immune response but viral proteins were not identified using this approach. Extracted CBPV RNAs were used for in vitro translation experiments. Despite several assays in varying experimental conditions, this approach has been unsuccessful. Another approach was to generate antibodies directed against different proteins or parts of viral proteins
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Xanidis, Nikos. "Exploring the implementation of Cognitive Behavioural Therapy for psychosis (CBTp) using the Normalisation Process Theory (NPT) framework." Thesis, University of Glasgow, 2018. http://theses.gla.ac.uk/30812/.
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Objective: Evidence suggests that only a minority of service users experiencing psychosis have access to Cognitive Behavioural Therapy for psychosis (CBTp). Normalisation Process Theory (NPT) is a theoretical framework which focuses on processes by which interventions are implemented and normalised in clinical practice. This study explored the views and experiences of mental health professionals regarding the implementation of CBTp. Barriers and facilitators to implementation were explored using the NPT framework. Design: A qualitative methodology was adopted involving semi-structured focus groups and individual interviews. Methods: A total of 14 members of staff working in the community and crisis mental health teams were recruited. Thematic analysis was used to generate initial themes. The Framework approach was utilised to map initial themes to the NPT framework. Results: Inductive coding generated five overarching themes consisting of 15 individual subthemes which captured the perceived barriers to engagement; contextual barriers to implementation; optimisation of implementation; positive attitudes towards implementation; and expectations of implementing CBTp. All but two subthemes mapped on to the NPT framework. The deductive analysis suggested that difficulties in making sense of CBTp among professionals were reflected as service level barriers which impeded wider implementation. Conclusion: The results of this study suggested a mixture of barriers and facilitators to CBTp implementation. Interpreting our findings within an NPT framework indicates the importance of strong clinical leadership to address difficulties in sense-making and service investment in CBTp.
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Hauser, Fabien. "Expression augmentée de la protéine de signalisation Cbp/PAG dans les lymphomes malins /." Genève : [s.n.], 2004. http://www.unige.ch/cyberdocuments/theses2004/HauserF/these.pdf.
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Zhang, Zuwen. "Functional analysis of the mouse CBP gene in the adult central nervous system." Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390810.
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