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Snow, Rachel Elizabeth. "Vâ†H gene usage by IgE in patients with atopic asthma." Thesis, University of Southampton, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266376.
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Neri, Elida Adalgisa. "Estudo da região promotora do gene do permutador Na+/H+ (NHE3)." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-01072009-104645/.
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Tendo em vista a importância do permutador Na+/H+ (isoforma 3) na reabsorção de NaCl e NaHCO3 em túbulos proximais e conseqüentemente no equilíbrio ácido-base e volume celular, surgiu o interesse em identificar a região promotora essencial para a transcrição do gene NHE3 e os elementos de ligação de fatores de transcrição presentes no mesmo, em células de túbulos proximais renais. Para isso, os segmentos da região flanqueadora 5´ do gene NHE3 de rato foram obtidos por PCR e inseridos no plasmídeo pGL3-basic, que codifica o gene repórter Firefly lucíferase. Os seguintes fragmentos foram analisados 1) -157 a +31; 2) -152 a +55; 3) -85 a +31; 4) -65 a +31; 5) -44 a +31; 6) -33 a +31; 7) -25 a +31; 8) -157 a +35, com deleção do elemento GATA (posição +20 a +23). Estes foram transfectados em células OKP, uma linhagem de túbulos proximais de rim de opossum. A atividade promotora de transcrição de cada segmento foi analisada em comparação com a atividade de luciferase observada com a transfecção do vetor pGL3-basic não recombinante, sem promotor. Foi realizado a cotransfecção do vetor pRL-CMV, que contém o gene da proteína repórter Renilla luciferase, usado como controle da eficiência de transfecção. Após serem analisados os resultados, observou-se que a atividade do promotor foi mais elevada com o constructo -152 a +55 (76.52 ± 45.26 (n=9)). Além disso, conseguimos identificar a existência de possíveis ativadores transcricionais no segmento entre a posição 85 e 65 (Egr-1/Sp1); 44 e 33 (Egr-1) e -33 e -25 (elemento TATA-Box não canônico), pois a remoção destes nucleotídeos reduziu significativamente a atividade do promotor. Outra observação foi a presença de elementos inibitórios entre as bases 65 e 44 (Sp1/Ap2), pois com a retirada destes, observamos um aumento muito significativo da atividade do promotor. O menor segmento (25/+31) apresentou atividade promotora significativa, sugerindo que ainda tenha os elementos indispensáveis para a montagem do complexo transcricional primário, embora com eficiência já bem reduzida. A presença do elemento GATA no primeiro exon, embora importante para a transcrição do gene NHE3 em células intestinais, não parece ser importante para a atividade transcricional em células de túbulos proximais.In view of the importance of the exchanger Na+/H+ (isoform 3), in reabsoption of NaCl and NaHCO3 in proximal tubules and consequently the acid-base balance, and cell volume, came the interest in identifying the region promoter essential for transcription of the NHE3 gene and the elements of the binding of transcription factors present in the same, in cells renal proximal tubules. For this, segments of the 5 flanking region of the rat NHE3 gene were obtained by PCR and inserted into pGL3-basic vector, which encodes Firefly luciferase reporter gene. The following fragments were analyzed 1) -157 to +31, 2) -152 to +55, 3) -85 to +31, 4) -65 to +31, 5) -44 to +31, 6) -33 to +31, 7) -25 to +31; 8) -157 to +35, with deletion of the GATA element (position +20 to +23). These were transfected in OKP cells, line of the renal proximal tubules of opossum kidney. The promoter activity of transcription of each segment was analyzed in comparison with the luciferase activity observed with transfection of the pGL3-basic vector recombinant, without promoter. Was performed cotransfecção of PRL-CMV vector, containing the gene of the reporter protein Renilla luciferase, used as internal control of the efficiency of transfection. After analyzing the results, observed promoter activity was higher with the construct -152 to +55 (76.52 ± 45.26 (n = 9)). Furthermore, we identify the possible existence of transcriptional activators in the segment between position -85 and -65 (Egr-1/Sp1), -44 and -33 (EGR-1) and -33 and -25 (atypical TATA-box element) because the removal of these nucleotides significantly reduced the activity of the promoter. Another observation was the presence of inhibitory elements between bases -65 and -44 (Sp1/Ap2), because with the deletion of these, we observed a very significant increase in the activity of the promoter. The lower segment (-25 / +31) showed significant promoter activity, suggesting that still has the elements essential for transcriptiption complex assembly of the primary, in spite of with reduced efficiency well. The presence of the GATA element in the first exon, although important for the transcription of the NHE3 gene in intestinal cells, does not appear to be important for transcriptional activity in cells of proximal tubules.
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Drezen, Jean-Michel. "Etude de la regulation in vivo du gene d'histocompatibilite h-2k." Paris 7, 1992. http://www.theses.fr/1992PA077053.
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L'expression du gene d'histocompatibilite de classe i h-2k est regulee a la fois dans les tissus de la souris adulte et au cours du developpement embryonnaire. Nous avons mesure le niveau d'expression de l'arn messager h-2k dans une serie de tissus de l'adulte et de l'embryon. Puis nous avons montre que les differents niveaux d'arn messagers observes sont lies a des differences d'activite transcriptionnelle du gene. La derniere partie de l'etude a consiste, en utilisant des souris transgeniques, a tester le role des differentes parties du gene h-2k dans son expression in vivo. La region 5 du gene est requise pour controler les niveaux d'arnm h-2k trouves dans les tissus de l'adulte. La region 3 du gene est impliquee dans le phenomene d'independance d'expression du transgene vis-a-vis de son site d'integration. La region interne du gene h-2k controle son expression au cours du developpement embryonnaire. Enfin l'intron 1 et ou l'intron 2 sont indispensables pour que le gene h-2k s'exprime in vivo.
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McAleer, Marcia Anne. "Structural analysis of the human gene for the complement control protein factor H." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.253471.
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Côté, Francine. "Expression of the human neurofilament heavy gene (NF-H) in transgenic mice." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=28718.
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Mammalian neurofilaments (NFs), the intermediate filaments (IFs) of nerve cells, are composed of three different polypeptides, commonly referred to as the low (NF-L), middle (NF-M) and heavy (NF-H) subunits. As members of the IF family and major components of large myelinated fibers, NFs have been assigned a putative role in maintaining the structural integrity of the neurons and in determining axonal caliber.To study the expression and function of the human NF-H gene, a genomic clone encompassing the human NF-H gene was isolated (Cos4NF-H) from a chromosome 22 enriched library and transgenic mice were generated. Four transgenic lines with multiple copies of the intact human NF-H gene were obtained. Northern blot analysis revealed that the human transgene was expressed specifically in neurons at level of approximately two-fold the endogenous mouse level. In addition, the human NF-H gene was expressed at the correct stage during the mouse nervous system development. Furthermore, expression of the human NF-H gene appeared to be proportional to gene copy-number and independent of the position of integration into the mouse genome. This is the first example of such a pattern of transgene expression in nerve cells. These results suggest that the regulatory signals necessary to direct the correct expression of the human NF-H gene lie within the injected clone and are recognized between the two mammalians species. Once identified, the control elements may constitute a valuable tool to direct the expression of foreign genes specifically to neurons.
The human NF-H transgenic mice appear normal at birth but progressively develop tremors and pathological features reminiscent of the ones observed in patients with amyotrophic lateral sclerosis (ALS). For instance, one sees selective enlargements of motor neuron perikarya, dorsal root ganglion (DRG) neurons and proximal axons in addition to distal axonal atrophy and muscle atrophy. Electron microscopy studies showed that the swellings consisted of intracytoplasmic accumulation of NFs. Axonal transport experiments were undertaken to determine if cytoskeletal elements were abnormally transported as has been suggested for a number of neurodegenerative diseases such as ALS. The proteins synthesized in motor/sensory neuron cell bodies were labeled and their subsequent transport to distal axonal segments was analyzed by SDS gels and fluorography. The results showed an impairment of axonal transport of NF proteins, actin and tubulin. There was also retention of some rapidly transported organelles. A possible mechanism to explain these results is that overexpression of the human NF-H gene led to neurofilamentous swelling formation that disrupted axonal flow and eventually resulted in motor neuron degeneration. The human NF-H transgenic mice are therefore a valuable model of human motor neuron disorders and can be used to test therapeutic strategies aimed at reducing the neurofilamentous swellings.
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Nazarenko, Irina. "Functional investigation of the class II tumor suppressor gene H-REV107-1." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969447094.
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DUGAST, ISABELLE. "Genetique moleculaire de l'hemochromatose idiopathique : etude du gene ferritine h du chromosome 6." Rennes 1, 1988. http://www.theses.fr/1988REN10062.
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Recherche d'une forme nouvelle de ferritine, attribuee au chromosome 6, dans la region du locus hi, marquee par les haplotypes hla. Mise en evidence d'un gene de grande taille dont les coupures enzymatiques suggerent la presence possible d'introns. Ce clone permet de decrire un polymorphisme possible du gene ferritine h sur le chromosome 6
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DAVID-WATINE, BRIGITTE. "Analyse de l'expression et de la regulation du gene q10, un gene h-2 de classe i a expression hepatospecifique." Paris 7, 1990. http://www.theses.fr/1990PA077240.
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Les genes de classe i du complexe majeur d'histocompatibilite (cmh) de la souris (h-2) constituent une famille de 25 a 40 genes situes sur le chromosome 17. Les produits de ces genes sont des glycoproteines transmembranaires associees de facon non covalente a la beta-2-microglobuline. Les antigenes de transplantation, tres polymorphes, sont les produits de 4 a 6 genes situes dans les regions h-2k, d et l; ils ont pour fonction de presenter des peptides antigeniques aux cellules t cd8+. D'autres molecules de type classe i sont codees par des genes situes dans les regions qa-tla et hmt, a l'exception des genes codant pour cd1 dont la localisation est inconnue. Ces molecules sont peu polymorphes, ont une distribution tissulaire particuliere et des niveaux d'expression peu elevee; leur role biologique n'est pas connu mais certaines de ces molecules sont reconnues par des cellules t gamma-delta et pourraient intervenir dans les interactions entre cellules t. Le gene q10 est un gene de la region qa qui presente deux singularites: il n'est exprime que dans le foie et code pour une molecule secretee. Nous avons d'abord analyse l'expression de ce gene chez l'adulte et au cours du developpement, et montre que les caracteristiques d'expression du gene q10 sont tres semblables a celles des genes codant pour des proteines seriques et exprimes dans le foie. Certaines caracteristiques de l'expression des antigenes de classe i chez l'embryon et dans les annexes embryonnaires ont ete egalement etudiees. Nous avons ensuite analyse les regions regulatrices du gene q10. En utilisant des extraits de proteines nucleaires de foie, plusieurs sites de fixation pour des facteurs, certains spefiques du foie, ont ete identifies. Un nouveau facteur, appele ta-f, a ete decrit dans le foie et le rein. Ce facteur interagit sous forme d'un dimere de 140 kilodatons avec les boites tata des genes q10 et h-2k#b. Enfin, nous avons montre que les regions importantes pour la regulation du gene h-2l#b et les sites de fixation pour des facteurs ubiquitaires sont en majorite alteres dans le promoteur de q10 et qu'inversement, les sites de fixation decrits dans le promoteur de q10 ne sont pas conserves dans les autres genes de classe i. Les consequences fonctionnelles de ces divergences de sequence sont des elements importants pour la comprehension des mecanismes de l'evolution des regions regulatrices dans une famille multigenique telle que les genes h-2 de classe i
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Giordanengo, Valérie. "Selection cellulaire par transfection d'un echanger na+/h+ mute resistant aux derives de l'amiloride." Nice, 1992. http://www.theses.fr/1992NICE6567.
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Wang, Bo. "Transcriptional regulation of the human NAD(P)H: quinone oxidoreductase gene during oxidative stress." Thesis, University of East Anglia, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262435.
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Kaloudas, Dimitrios. "Structure, evolution and expression of the H-Box/NC gene family of Arabidopsis thaliana." Thesis, University of Essex, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410235.
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Melo, Cynthia Farias Vieira de. "Análise do perfil de metilação dos genes THBS1, GPX3 e COX2 e identificação de H. pylori em amostras de câncer gástrico." Universidade Federal da Paraíba, 2013. http://tede.biblioteca.ufpb.br:8080/handle/tede/3645.
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Previous issue date: 2013-05-16Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Cancer is a disease with a high mortality rate in Brazil, including, stomach cancer is currently the fourth most common type of cancer worldwide, responsible for countless deaths. Its etiology is multifactorial, because studies suggest associations to various factors such as dietary habits, environmental factors, genetic and epigenetic factors and gastric infection by Helicobacter pylori. Epigenetic changes such as methylation of the promoter regions of genes involved in cellular homeostasis may contribute to gastric carcinogenesis. To verify the methylation status of THBS1, GPX3 and COX2 genes and to evaluate their association with H. pylori in gastric adenocarcinomas, Methylation-Sensitive Restriction Enzyme PCR (MSRE-PCR) assay was performed in 39 gastric carcinomas (intestinal and diffuse types) and 15 normal stomach tissue samples. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analysies were performed using Fisher s exact test. The hypermethylation of GPX3, THBS1 and COX2 occurred in 18% (n = 7), 5% (n = 2) 36% (n = 14) of gastric cancer samples, respectively, whereas in normal samples was found in 13%, 7% and 67%. The presence of H. pylori was detected in 67% of gastric cancer samples and 67% in normal gastric samples. No correlation was found between the methylation profile of the studied samples and clinicopathological variables and the presence of H. pylori (P ≥ 0,05). The presence of H. pylori in gastric cancer samples and normal was not associated with clinicopathologic variables analyzed (P> 0.05).
O câncer é uma doença com alta taxa de mortalidade no Brasil, dentre eles, o câncer de estômago constitui atualmente, o quarto tipo de câncer mais comum a nível mundial. No ano de 2012, estimam-se, para o Brasil, 12.670 casos novos de câncer do estômago em homens e 7.420 em mulheres. A sua etiologia é multifatorial, pois estudos sugerem associações a diversos fatores como: hábitos alimentares, fatores ambientais, fatores genéticos e epigenéticos e a infecção gástrica por Helicobacter pylori. Alterações epigenéticas tais como a metilação das regiões promotoras de genes envolvidos na homeostase celular podem contribuir para carcinogênese gástrica. Para verificar o estado de metilação de genes THBS1, GPX3 e COX2 e avaliar a sua associação com a Helicobacter pylori (H. pylori) em adenocarcinomas gástricos, Methylation-Sensitive Restriction Enzyme PCR (MSRE-PCR) foi realizada em 39 carcinomas gástricos (intestinal e tipo difusa) e 15 amostras de tecido normal do estômago. A presença de H. pylori foi realizada por amplificação de um fragmento de rRNA 16S. Analysies estatísticas foram realizadas utilizando o teste exato de Fisher. A hipermetilação de GPX3, THBS1 e COX2 ocorreu em 18% (n = 7), 5% (n = 2) 36% (n = 14) das amostras de câncer gástrico, respectivamente, ao passo que em amostras normais foi encontrada em 13%, 7 % e 67%. A presença de H. pylorifoi detectada em 67% das amostras de câncer gástrico e 67% em amostras gástricas normais. Não foi encontrada correlação entre o perfil de metilação das amostras estudadas com variáveis clínico-patológicas e com presença de H. pylori (P > 0,05). A presença de H. pylori nas amostras de câncer gástrico e normais não foi associada com as variáveis clínico-patológicas analisadas (P > 0.05).
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Childs, Richardo. "Fetal gene therapy : balancing ethical theory, scientific progress and the rights of others." Thesis, Cardiff University, 2012. http://orca.cf.ac.uk/46405/.
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This thesis examines the relationship between rights and duties in the field of fetal gene therapy and assesses if the current regulatory position within England and Wales is compatible with the intergenerational aspects of scientific progress within fetal gene therapy (FGT). Within the field of genomics, the fetal junction has become a site where gene therapists are developing a range of medical techniques, such as fetal gene therapy and in utero stem cell therapy. Utilising such techniques raises questions about the intergenerational aspects of scientific progress and how intergenerational rights can reshape regulation. The thesis focuses upon these key questions: Are the intergenerational issues of FGT taken into account by both direct and indirect stakeholders? Can intergenerational issues override the reproductive rights of the mother? Have intergenerational issues impacted upon the clinical applications implicit and manifest in this work? Addressing such questions is important because the conflict between the rights of the mother, fetus, clinical researchers and society have the potential to delay progress in FGT. In addressing these questions the thesis utilised thematic analysis of relevant regulatory institutional documents, from international declarations to regulatory guidelines; and semi structured interviews of identified FGT practitioners to identify areas of potential conflict. Following the data collection and analysis, the field data identified five key areas of potential conflict, which were then assessed using the Principle of Generic Consistency (PGC) as proposed by Alan Gewirth (1978) and later altered by Beyleveld and Brownsword (2001). The thesis will argue that the field data shows that established regulatory principles such as human dignity are of limited value in relation to FGT. In other areas such as informed choice, autonomy and intergenerational equity the PGC is applied to define and partially resolve the outstanding areas necessary for consistent ethical and regulatory guidance in FGT
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Ciriello, Simona [Verfasser], and Niels H. [Akademischer Betreuer] Gehring. "Separate functions of BTZ during post-transcriptional gene regulation / Simona Ciriello. Gutachter: Niels H. Gehring." Köln : Universitäts- und Stadtbibliothek Köln, 2014. http://d-nb.info/1069985805/34.
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Kang, Yeon-Joo. "Transcriptional regulation of prostaglandin H synthase (PGHS)-2 gene in a macrophage model of inflammation." Diss., Connect to online resource - MSU authorized users, 2006.
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Rosa, Gislaine Nonino 1974. "Cinomose canina : detecção e análise filogenética do gene hemaglutinina (H) em amostra clínicas e necroscópicas." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316614.
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Orientador: Clarice Weis ArnsDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: A cinomose canina tem sido relatada como uma das mais importantes doenças infecto contagiosas dos canídeos selvagens e domésticos. É causada por um agente viral denominado vírus da cinomose canina (CDV). Os vírus pertencem à família Paramyxoviridae , gênero Morbillivirus. São vírus envelopados, com genoma composto por uma fita simples de RNA, polaridade negativa, não segmentado. Alto grau de variabilidade genética no gene da hemaglutinina ( H) tem sido encontrada entre estirpes virais recentes e vacinais, e estas variações podem estar relacionadas ao aumento da ocorrência global da cinomose. No presente estudo, amostras biológicas de cães com sintomatologia sugestiva da cinomose foram analisadas geneticamente. Para a detecção de um fragmento de 882 pb do gene H do CDV padronizou-se uma RT-PCR que mostrou-se capaz de amplificar o material genético viral em amostras de urina, líquido céfalo-raquidiano, sistema nervoso central (SNC), baço , pulmão , fígado , rins, linfonodos, bexiga e timo. As amostras positivas de acordo com a RT-PCR foram encaminhadas para o sequenciamento e análise filogenética. Os resultados encontrados sugerem que estas amostras assemelham-se geneticamente aos vírus agrupados nas linhagens Européia e Ásia-1. A estirpe vacinal Lederle, utilizada como padrão, foi agrupada junto a linhagem América-1 onde encontram-se todas as estirpes vacinais , também conhecidas como "Old CDVs" . Os achados deste trabalho apontam para a ocorrência de estirpes geneticamente distintas daquelas utilizadas na produção de vacinas e mais estudos são necessários para a avaliação da eficácia das vacinas disponíveis, propiciando um melhor controle da doença
Abstract: Canine distemper has been reported as one of the most important infectious diseases of wild and domestic canids. It is caused by a viral agent called canine distemper virus (CDV). Viruses belonging to the family Paramyxoviridae, genus Morbillivirus. They are enveloped viruses with genome composed of a single strand of RNA, negative polarity, not segmented. High degree of genetic variability in the gene for hemagglutinin (H) has been found between recent viral strains and vaccination strains, and these variations may be related to increased overall occurrence distemper. In this study, biological samples from dogs with symptoms suggestive of distemper were analyzed genetically. For the detection of a 882 base pairs (bp) fragment of the gene of CDV H was standardized a RT-PCR wich proved to be capable of amplifying the viral genetic material in urine, cerebrospinal fluid, central nervous system (CNS), spleen , lungs, liver, kidneys, lymph nodes, bladder and thymus. Positive samples according to RT-PCR were sent for sequencing and phylogenetic analysis. The results suggest that these samples are similar to viruses genetically clustered lineages in European and Asia-1. The Lederle vaccine strain, used as standard, was grouped with Latin-1 lineages which are all vaccine strains, also known as "old CDVs." The findings of this study point to the occurrence of genetically distinct strains from those used in vaccine production and more studies are needed to assess the efficacy of vaccines available, providing better control of the disease
Mestrado
Microbiologia
Mestra em Genética e Biologia Molecular
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Sousa, Jair Mois?s de. "Adaptabilidade de h?bridos entre Gossypium barbadense E G. hirsutum N contendo o gene cry1Ac." Universidade Federal do Rio Grande do Norte, 2009. http://repositorio.ufrn.br:8080/jspui/handle/123456789/16762.
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Previous issue date: 2009-02-27Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Hybrids among transgenic plants and related species are expected to occur if they are sympatric and when there are not crossing barriers; as is the case, in Brazil, of cry1Ac transgenic cotton and Gossypium barbadense. This species has been maintained as dooryard plants, and should be preserved as a genetic resource. Hybrids were evaluated about traits related to fitness, leading to infer about its chances of survivor and selection. A barbadense genotype collected at the state of Mato Grosso was outcrossed to the variety DP 404, containing the gene cry1Ac, and to the isoline DP 404. All the F1 individuals and 122 among 170 F2 individuals expressed the toxin, and presented levels of resistance to pink bollworm (Pectinophora gossypiella) and cotton leafworm (Alabama argillacea) equivalent to the transgenic parent and superior to the isoline, barbadense or non transgenic hybrids. The percentage of germination and number of days to germinate did not differ among genotypes. Anthesis of the first flower and opening of the first cotton boll occurred earlier for herbaceous cotton and F1 hybrids than F2 population in average; all the populations presented a number of days to flower and opening of the first boll smaller then barbadense. The highest plants were barbadenses, and herbaceus the smallest, with F1 and F2 populations presenting intermediary heights. The number of seeds per plants were superior for F1 hybrids an herbaceous cotton, F2 populations were in average intermediary; the barbadense genotype produced the smallest number of seeds per plant. Pink bollworm, mainly, and also cotton leafworm, are important barbadense pests, so the transgene positive effect could favor the selection of hybrids, and hence G. hirsutum genome, against the maintenance of pure G. barbadense genome. The selection may be influenced by the plant uses: the smaller size of hybrids when compared to the barbadense may lead them to be differentiated from these parents to which medicinal properties are attributed; on the other hand, the greater boll production may favor hybrids maintenance with the purpose of producing lamp wicks, or use as an ornamental or swab
Espera-se que hibrida??es entre plantas transg?nicas e esp?cies pr?ximas ocorram sempre que haja simpatria e n?o existam barreiras de cruzamento, como ? o caso, no Brasil, do algodoeiro contendo o gene cry1Ac e a esp?cie Gossypium barbadense. Os barbadenses v?m sendo mantidos em quintais, e ? importante sua preserva??o como recurso gen?tico. H?bridos foram avaliados para caracteres relacionados com a adaptabilidade, inferindo sobre suas chances de sobreviv?ncia e sele??o. Para isto, obtiveram-se plantas F1 e F2 do cruzamento entre um algodoeiro barbadense coletado no estado de Mato Grosso com as cultivares DP404, contendo cry1Ac, e de sua isolinha DP4049. Todos os 37 indiv?duos F1 e 122 dentre 170 indiv?duos F2 avaliados expressaram cry1Ac, e apresentaram n?veis de resist?ncia ?s lagartas rosada (Pectinophora gossypiella) e curuquer?-doalgodoeiro (Alabama argillacea) equivalentes ao parental transg?nicos e superiores a isolinha, barbadense e h?bridos que n?o continham o transgene. N?o foram observadas diferen?as significativas para a porcentagem de germina??o ou quantidade de dias para germina??o. O florescimento e abertura do primeiro capulho ocorreram mais cedo nos algodoeiros herb?ceos e nos h?bridos que nas popula??es F2 em m?dia; todas as popula??es apresentaram um n?mero de dias para o florescimento e abertura do primeiro capulho significativamente mais baixo que os barbadenses. As plantas mais altas na matura??o eram os barbadenses, e os herb?ceos as mais baixas, sendo as popula??es F1 e F2 intermedi?rias. O n?mero de sementes por planta foi superior nos h?bridos F1 e algodoeiros herb?ceos, sendo as popula??es F2 intermedi?rias em m?dia, e os barbadenses aqueles que produziram menor n?mero de sementes. A lagarta rosada, principalmente, e tamb?m a curuquer?-do-algodoeiro s?o importantes pragas de G. barbadense, portanto o efeito positivo do transgene pode favorecer a sele??o de h?bridos contendo o transgene, e deste modo favorecer plantas que cont?m genoma de G. hirsutum, em detrimento da pureza do genoma de barbadense. A sele??o deve ser influenciada pelos usos da planta: o fato de os h?bridos serem mais baixos pode diferenci?-los dos pais barbadenses aos quais a propriedades medicinais s?o atribuidas; por outro lado, a produ??o bem maior de capulhos pode favorecer a manuten??o dos h?bridos quando se visa confec??o de pavios ou ornamenta??o de quintais e jardins
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Figueiredo, Frederico de Castro. "Estudo do gene da proteína de ligação de ácidos graxos - coração (H-FABP) em suínos." Universidade Federal de Viçosa, 2004. http://www.locus.ufv.br/handle/123456789/10478.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
Objetivou-se, neste trabalho, detectar variantes alélicas do gene da Proteína de Ligação de Ácidos Graxos - Coração para construção de mapas de restrição e estudar as associações entre as variantes detectadas e características quantitativas avaliadas em animais F2, para possíveis aplicações em programas de melhoramento genético de suínos. A Proteína de Ligação de Ácidos Graxos - Coração (H-FABP), produto do gene FABP3, é uma proteína da família das FABPs. O gene, que está localizado no cromossomo suíno seis, foi seqüenciado em animais parentais de um cruzamento F2 entre varrões da raça nativa brasileira Piau e fêmeas comerciais (Landrace x Large White x Pietrain). Os animais tiveram seu DNA extraído de células brancas do sangue e amplificado por meio da reação de polimerização em cadeia (PCR). Os primers usados na reação foram desenhados para amplificar os quatro éxons do gene. Os fragmentos amplificados foram seqüenciados em sequenciador automático ABI PRISM 310 (Applied biosystems). Os fragmentos gerados foram comparados com a seqüência do gene depositada no GenBank. Foram notadas divergências entre as seqüências geradas e as do GenBank, tanto em alguns animais Piau quanto em algumas fêmeas comerciais. Essas alterações serviram como marcas para associações dos polimorfismos desse gene, com características quantitativas. Construiu-se um mapa de restrição, permitindo a identificação de enzimas que reconhecessem as alterações nas seqüências analisadas. Neste estudo, utilizou-se a enzima de restrição Hinf I, que reconheceu o sítio polimórfico presente no primeiro fragmento amplificado, na posição 108, caracterizado pela deleção de uma base Timina (T). Foram genotipados 246 animais F2 por meio da reação de restrição. Dois genótipos foram identificados, sendo 198 animais HH e 48 animais Hh. O polimorfismo estudado apresentou efeito significativo para as características: peso aos 63 dias de idade (p=0,1528), idade ao abate (p=0,0110), comprimento de carcaça pelo método americano (p=0,1789), espessura de toucinho imediatamente após a última costela (p=0,0449), espessura de toucinho entre a última e a penúltima vértebra lombar (p=0,1199), espessura de toucinho medida na carcaça direita resfriada na região da última costela, a partir de corte transversal no carré, a 6,5cm da linha dorso-lombar (p=0,1377), comprimento do intestino (p=0,0287), peso total de copa (p=0,1623), peso da copa sem pele e sem capa de gordura (p=0,1271), peso total de carré (p=0,0442), peso de papada (p=0,0195), peso de filezinho (p=0,0867), peso de rim (p=0,0028) e pH 45 minutos após o abate (p=0,1256). Os resultados obtidos indicam que o gene da H-FABP possui potencial para aplicação em programas de seleção assistida por marcadores moleculares para características de interesse econômico na cadeia produtiva de suínos.
The objectives of this study were to identify genetic polymorphisms in the Heart Fatty Acid Binding Protein gene for construction of restriction maps and to study associations between the polymorphisms detected and quantitative traits evaluated in F2 animals, to use in genetic improvement in animal production. The Heart Fatty Acid Binding Protein (H-FABP), the product of the gene FABP3, is a protein of the family of the FABPs. This gene, that is located in the swine chromosome number six, was sequenced in parental animals of a F2 crossing between boars of the Brazilian native breed Piau and commercial sows (Landrace x Large White x Pietrain). The DNA of animals was extracted of white cells of blood and amplified by Polymerase Chain Reaction (PCR). Primers used in the reaction were drawn to amplify four exons of the gene. The PCR products were sequenced in ABI PRISM 310 (Applied biosystems). The sequences were compared with the sequence of the gene deposited in the GenBank. Divergences between the generated sequences and the GenBank sequences were noticed in both genetics groups. A restriction map was constructed allowing the identification of enzymes that recognize the alterations in the analyzed sequences. In this study, was used enzyme of restriction Hinf I, that recognize the polymorphism in the position 108 in sequence I, characterized by the absence of a Thymine (T). Using the restriction reaction, 246 F2 animals were genotyped. Two genotypes were identified, 198 HH animals and 48 Hh animals. The polymorphism was significantly associated with: weight at 63 days of age (p=0.1528), slaughter age (p=0.0110), carcass length by the american carcass classification method (p=0.1789), backfat thickness after last rib (p=0.0449), backfat thickness between last 1st-2nd lumbar vertebrae (p=0.1199), backfat thickness after last rib, at 6.5 cm from the midline (p=0.1377), intestine length (p=0.0287), total boston shoulder weight (p=0.1623), skinless and fatless boston shoulder weight (p=0.1271), loin (bone- in) weight (p=0.0442), jowl weight (p=0.0195), sirloin weight (p=0.0867), kidney weight (p=0.0028) and pH evaluated at 45 minutes after slaughter (p=0.1256). These results show that H-FABP gene has potential for application in programs of marker assisted selection for quantitative traits in swine.
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Mavathur, Nanjundaiah Ramesh [Verfasser]. "Coordinated regulation of gene expression by E.coli chromatin proteins FIS and H-NS / Ramesh Mavathur Nanjundaiah." Bremen : IRC-Library, Information Resource Center der Jacobs University Bremen, 2008. http://d-nb.info/1034967592/34.
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Goto, Norimoto. "No association between complement factor H gene polymorphism and exudative age-related macular degeneration in Japanese." Kyoto University, 2011. http://hdl.handle.net/2433/151916.
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GOSSE, BRUN SANDRINE. "Etude du polymorphisme du gene h-ras dans le risque des cancers du sein et du colon." Clermont-Ferrand 2, 1998. http://www.theses.fr/1998CLF22006.
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Le polymorphisme du gene h-ras jouerait un role important dans la susceptibilite des cancers. Ce travail rapporte l'evaluation d'une nouvelle approche methodologique pour l'etude de la diversite allelique du minisatellite h-ras dans le risque des cancers mammaires (cm, 123 cas), des cancers colorectaux (cc, 142 cas) par comparaison avec une population saine (143 sujets), puis l'identification des alterations somatiques a ce locus susceptibles d'etre impliquees dans la carcinogenese. Apres modification des parametres d'amplification (pcr) du minisatellite h-ras, nous avons experimente le potentiel d'utilisation d'un sequenceur d'adn. L'utilisation d'une matrice hydrolink dans des conditions denaturantes a permis d'augmenter la resolution des grands fragments. Cependant, a ce jour des incertitudes subsistent dans la validation d'une methodologie standardisee sur un sequenceur d'adn. Pour la suite de notre etude, nous avons alors choisi d'utiliser la technique de pcr combinee au sequencage de certains alleles. Une distribution allelique constitutionnelle statistiquement differente a ete observee entre la population de cm, de cc et la population saine, resultant de l'augmentation de la frequence totale des alleles rares chez les patients atteints de cancer. 9% des patients, quel que soit le type de cancer, possedent un allele rare contre 1,4% des sujets sains. De plus, certains alleles apparaissent specifiquement associes au risque de cancer. Aucune correlation n'a ete trouvee entre les alleles rares et les criteres cliniques ou la localisation des tumeurs. La perte d'un allele h-ras dans les tumeurs, a ete retrouvee dans 5% des cc, 6,7% des cm, et une instabilite somatique a ce locus dans 0,7% des cc et 6,5% des cm. Nous avons demontre que les alleles rares h-ras augmentaient le risque de developper un cm ou un cc et que les alterations somatiques a ce locus ne sont pas des evenements genetiques majeurs impliques dans les neoplasies mammaires et coliques.
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Counillon, Laurent. "L'echangeur na#+/h#+ nhe1, structure du gene, regulation hormonale et identification du site de liaison de l'amiloride." Nice, 1993. http://www.theses.fr/1993NICE4620.
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L'echangeur na#+/h#+ nhe1 est une proteine transmembranaire, ubiquitairement exprimee dans les cellules eucaryotes. Ce transporteur, active par les facteurs de croissance et bloque par un diuretique antihypertenseur, l'amiloride, joue un role crucial dans la regulation du ph et du volume cellulaires. D'autres isoformes (nhe2, nhe3), exprimees sur la face apicale de cellules epitheliales de rein et d'intestin possedent une sensibilite plus faible pour l'amiloride et sont specialisees dans les transports transepitheliaux. L'identification d'acides amines impliques dans l'interaction des echangeurs na#+/h#+ avec l'amiloride a ete rendue possible par l'approche genetique suivante: 1) clonage de l'adnc codant pour l'isoforme nhe1 des fibroblastes ar300 selectionnes pour leur resistance a l'amiloride. Ces cellules surexpriment un echangeur mute ayant une affinite reduite pour cet inhibiteur; 2) identification d'une mutation ponctuelle (l167f) dans le quatrieme domaine transmembranaire de l'echangeur par comparaison de sequence entre l'adnc codant pour l'echangeur mute et l'adnc sauvage. Cette seule mutation est responsable de la diminution d'affinite pour l'amiloride; 3) des experiences de mutagenese dirigee ont permis de localiser un autre residu de l'echangeur (f165) intervenant dans le transport du sodium et dans l'interaction avec l'amiloride; 4) il a ete demontre que l'acquisition du phenotype de resistance des cellules ar300 s'est faite par l'apparition de la mutation l167f sur un des deux alleles de l'echangeur, puis par amplification genique de l'allele mute. Cet adnc mute conferant une resistance a l'amiloride a ete utilise comme marqueur pour la construction d'un vecteur universel de selection pour cellules eucaryotes. Un nouvel inhibiteur aux proprietes anti-ischemiques a ete teste sur les isoformes nhe1, nhe2 et nhe3. Il s'est revele beaucoup plus discriminatif que l'amiloride et ses derives 5-n substitues. Le gene de l'echangeur na#+/h#+ nhe1 a ete clone. Son organisation en introns et exons a ete determinee. L'identification de son promoteur a permis la mise en evidence de sites consensus de liaison pour certains facteurs de transcription
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Hammerle-Fickinger, Andréa [Verfasser], Heinrich H. D. [Akademischer Betreuer] Meyer, Michael W. [Akademischer Betreuer] Pfaffl, and Karl [Akademischer Betreuer] Kramer. "Differential gene expression during pre-implantation pregnancy in bos taurus / Andréa Hammerle-Fickinger. Gutachter: Michael W. Pfaffl ; Heinrich H. D. Meyer ; Karl Kramer. Betreuer: Heinrich H. D. Meyer." München : Universitätsbibliothek der TU München, 2012. http://d-nb.info/1024567362/34.
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Li, Jing. "Targeted degradation of RNA by RNase H using stable DNA hairpin oligomers and a study on the effect of temperature and divalent cations on RNA conformational states." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/25213.
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Marques, Ariadne. "Identifica??o de genes diferencialmente expressos em h?bridos de Eucalyptus inoculados com isolados de Ceratocystis fimbriata." UFVJM, 2013. http://acervo.ufvjm.edu.br:8080/jspui/handle/1/341.
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Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES)
O Ceratocystis fimbriata Ellis & Halsted ? um fitopat?geno vascular de ampla distribui??o geogr?fica e gama de hospedeiros. A murcha de Ceratocystis em Eucalyptus ? considerada de dif?cil controle devido ao seu car?ter sist?mico e a variabilidade gen?tica dos isolados. O plantio de material resistente ? a principal forma de controle desta doen?a. No entanto, a obten??o de material gen?tico resistente pode demandar longos per?odos em um programa de melhoramento. A identifica??o de gen?tipos resistentes dentre os clones utilizados comercialmente pode ajudar a abreviar o tempo necess?rio ao melhoramento. Assim, objetivou-se avaliar a resist?ncia de clones de eucalipto ? murcha de Ceratocystis, analisar as respostas ecofisiol?gicas desses clones sob infec??o e fornecer suporte ao processo de melhoramento gen?tico para tal caracter?stica. Foram avaliados 27 clones de resist?ncia desconhecida e 2 clones caracterizados como resistente e suscet?vel ? murcha de Ceratocystis, todos inoculados artificialmente com isolados de C. fimbriata. Os 27 clones apresentaram, aos 50 dias ap?s inocula??o, varia??o quanto ? resist?ncia ? doen?a. Os dois clones de resist?ncia conhecida tiveram crescimento, ?ndice de clorofila e efici?ncia qu?ntica do fotossistema II (Fv/Fm) avaliados em quatro diferentes tempos. As vari?veis analisadas apresentaram potencial para uso na avalia??o da resist?ncia/suscetibilidade de gen?tipos de Eucalyptus spp. ? murcha de Ceratocystis. O clone resistente (R) e o suscet?vel (S) foram utilizados para a constru??o de uma biblioteca subtrativa supressiva.
Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Ci?ncia Florestal, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2013.
ABSTRACT The Ceratocystis fimbriata Ellis & Halsted is a vascular phytopathogen of wide geographic distribution and host range. Ceratocystis wilt in Eucalyptus is considered difficult to control due to its systemic character and the genetic variability of the isolated. Planting resistant material is the main way to control this disease. However, the acquisition of genetic material resistant may require long periods in a breeding program. The identification of resistant genotypes among clones used commercially can help shorten the time needed to improve. The aim was to evaluate the resistance of eucalyptus clones to Ceratocystis wilt, analyze the ecophysiological responses of these clones under infection and provide support to the process of breeding for this trait. We evaluated 27 clones of unknown resistance and 2 clones characterized as resistant and susceptible to Ceratocystis wilt, all artificially inoculated with isolates of C. fimbriata. The 27 clones showed, 50 days after inoculation, variation in disease resistance. The two clones of known resistance grew, chlorophyll content and quantum efficiency of photosystem II (Fv / Fm) evaluated at four different times. The variables analyzed showed potential for use in the evaluation of the resistance/susceptibility of genotypes of Eucalyptus spp. to Ceratocystis wilt. The clone resistant (R) and susceptible (S) were used for the construction of a suppressive subtractive library.
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Kissa, Maria [Verfasser], Michael [Akademischer Betreuer] Schroeder, and Nigam H. [Akademischer Betreuer] Shah. "CASSANDRA: drug gene association prediction via text mining and ontologies / Maria Kissa. Gutachter: Michael Schroeder ; Nigam H. Shah." Dresden : Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2015. http://d-nb.info/106909305X/34.
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Leite, Gabriella Duarte Queiroz. "Efeitos crônicos da angiotensina II sobre a atividade e expressão da isoforma 3 do trocador Na+/H+." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/42/42137/tde-21072011-151842/.
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NHE3 reabsorve a maior parte de Na+ em túbulos proximais e é agudamente modulado por Ang II de forma bimodal. O objetivo deste trabalho foi avaliar os efeitos crônicos da Ang II sobre a atividade, expressão e atividade promotora de NHE3. A atividade de NHE3 foi avaliada na presença de veículo, inibidor de NHE1, 2 e 3 e H+ ATPase. Houve redução da recuperação do pHi na presença do inibidor de NHE3. Células foram expostas por 24h a Ang II de 10-7M a 10-12 M e houve aumento de atividade com Ang II 10-11 M. Houve aumento na expressão de NHE3 e no seu RNAm. Actinomicina D não mostrou diferença entre os tempos de ½ vida do RNAm. Transfecções transitórias de fragmentos do promotor de NHE3 de rato mostraram que a atividade do fragmento -65/+31 aumentou na presença de Ang II. Mutações em sítios para a ligação de Sp1/Egr-1 e AP2 mostraram que o sítio Sp1/Egr-1 é fundamental para esse efeito. As vias que envolvem o citocromo P450, PI3K, PKA e MAPK são ativadas, porém, as vias da PLC e JAK/STAT não. Losartan aboliu os efeitos observados. Conclui-se que a exposição crônica à baixa concentração de Ang II promoveu aumento na atividade, expressão, nível de RNAm e atividade promotora do gene NHE3 via AT1R. O sítio de ligação para os fatores de transcrição Sp1/Egr-1 está envolvido nessa resposta.NHE3 is the major responsible for the sodium reabsorption in proximal tubules and it is Ang II acutely modulated in a bimodal fashion. The aim of this study was to evaluate the chronic effects of Ang II on NHE3 activity, transcription and expression. The NHE3 activity was evaluated in the presence of vehicle, NHE1, 2 and 3 and H+ ATPase inhibitors. Presence of NHE3 inhibitor reduced the rate of pHi recovery. Cells were treated with Ang II 10-7M to 10-12 M for 24h and Ang II 10-11 M increased the pHi recovery rate. NHE3 protein and mRNA were increased in Ang II presence. NHE3 mRNA ½ life in Actinomycin D incubated cells was not affected by Ang II treatment. Transient transfections of fragments of rat NHE3 promoter showed that the activity of -65/+31 was increased in Ang II presence. Mutation at Sp1/Egr-1 and AP2 sites in the -60/+31 fragment showed that Sp1/Egr-1 integrity is required. Cytochrome P450, PI3K, PKA and MAPK signaling pathways are related with this effect, while PLC and JAK/STAT are not. Losartan abolished the observed effects. In conclusion, chronic treatment with low concentration of Ang II resulted in increase of NHE3 activity, protein expression, mRNA levels and promoter activity of NHE3 gene through AT1R. Sp1/Egr-1 site seems to be involved in this effect.
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Medina, Flavio Mac Cord 1978. "Associação do polimorfismo Y402H do gene CFH com o tratamento da degeneração macular relacionada à idade com antiangiogênicos." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310113.
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Orientador: José Paulo Cabral de VasconcellosTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O fator de complemento H (CFH) é um componente do sistema imunológico que possui ação imunomoduladora sobre a resposta inflamatória. A gravidade da degeneração macular relacionada à idade (DMRI) é determinada em parte por um estado inflamatório sustentado por atividade aberrante da via alternativa do complemento. As evidências na literatura da relação entre o polimorfismo Y402H do gene CFH e a resposta ao tratamento da DMRI exsudativa permanecem controversas. Objetivo: Avaliar a associação entre as variantes do polimorfismo Y402H do gene CFH e os efeitos funcional e morfológico a curto prazo, assim como a evolução a longo prazo, dos antiangiogênicos em pacientes com DMRI exsudativa. Métodos: Vinte e cinco pacientes recém diagnosticados com DMRI exsudativa foram avaliados em um estudo de curto prazo com acuidade visual medida pela tabela do ETDRS e espessura retiniana central por tomografia de coerência óptica (OCT) de alta resolução, submetidos a injeção intravítrea de bevacizumabe e prospectivamente reexaminados em 7 e 28 dias. Quarenta e seis pacientes previamente submetidos ao tratamento com antiangiogênicos tiveram seus prontuários e exames retrospectivamente avaliados em um estudo de longo prazo quanto às evoluções funcional e morfológica ao longo de um ano. Esses parâmetros foram comparados com o genótipo do CFH, cuja análise molecular do polimorfismo Y402H foi realizada por meio da reação em cadeia da polimerase (PCR) e sequenciamento direto. Resultados: No estudo de curto prazo, houve melhora da acuidade visual no dia 28 em relação ao valor inicial (D0 vs. D28) em todos os genótipos. Entretanto, no grupo homozigoto para o alelo de risco (CC), ocorreu diferença apenas no dia 28 em relação ao dia 7 (D7 vs. D28), enquanto nos grupos CT e TT, a acuidade visual melhorou mais precocemente, no dia 7 em relação ao valor inicial (D0 vs. D7). A espessura retiniana central apresentou redução nos grupos CT (D0 vs. D7 e D0 vs. D28) e TT (D0 vs. D28), enquanto não houve mudança significativa no grupo CC. No estudo de longo prazo, foi evidenciada melhora da acuidade visual ao longo de um ano de acompanhamento apenas no grupo de pacientes sem o alelo C, sem diferença significativa no grupo de pacientes com o alelo de risco. A espessura retiniana central apresentou redução nos genótipos CT e TT, enquanto que no grupo CC não houve significância. Número de injeções, persistência de atividade neovascular e percepção subjetiva de melhora não diferiram entre os genótipos. Conclusão: O perfil de genótipo do CFH parece influenciar o efeito funcional e morfológico da injeção intravítrea de bevacizumabe com uma ação mais precoce em pacientes sem o genótipo de risco. A presença do alelo de risco parece estar relacionada à ausência de melhora visual ao longo de um ano de tratamento com inibidores do VEGF. Esses resultados sugerem que o perfil do genótipo do CFH possa exercer efeito farmacogenético nesse grupo de pacientes brasileiros, influenciando negativamente a resposta ao tratamento da DMRI exsudativa com antiangiogênicos
Abstract: Introduction: The complement factor H (CFH) is a component of the immune system that has immunomodulatory action on the inflammatory response. The severity of age-related macular degeneration (AMD) is determined in part by an inflammatory state sustained by aberrant activity of the alternative complement pathway. Evidences in the literature of the relationship between the Y402H polymorphism of CFH gene and response to treatment of wet AMD remain controversial. Purpose: To evaluate the association between variants of the Y402H polymorphism of CFH gene polymorphism and the short-term functional and morphological effects, as well as long-term evolution, of antiangiogenic drugs in patients with exudative AMD. Methods: Twenty-five patients with newly diagnosed exudative AMD were evaluated in a short-term study with visual acuity on ETDRS chart and central retinal thickness measured with high resolution optical coherence tomography (OCT), underwent intravitreal injection of bevacizumab and were prospectively reviewed in 7 and 28 days. Forty-six patients previously submitted to treatment with VEGF inhibitors had their medical charts retrospectively evaluated in a long-term study about the functional and morphological evolutions over one year. These parameters were compared with the CFH genotype, whose molecular analysis of Y402H polymorphism was performed by polymerase chain reaction (PCR) and direct sequencing. Results: In the short-term study, there was improvement in visual acuity at day 28 compared to baseline (D0 vs. D28) in all genotypes. However, in the group homozygous for the risk allele (CC), differences occurred only on day 28 compared to day 7 (D7 vs. D28), while the CT and TT groups, visual acuity improved earlier in the day 7 compared the initial value (D0 vs. D7). The central retinal thickness decreased in groups CT (D0 vs. D7, D0 vs. D28) and TT (D0 vs. D28), while there was no significant change in group CC. In the long-term study, it was noticed improvement in visual acuity over one year of follow-up in the group of patients without the C allele and no significant difference in the group of patients with the risk allele. The central retinal thickness decreased in the CT and TT genotypes, whereas in the CC group the difference was not significant. Number of injections, persistent neovascular activity and subjective perception of improvement did not differ between genotypes. Conclusion: The profile of the CFH genotype seems to influence the functional and morphological effect of intravitreal injection of bevacizumab with an earlier action in patients without the risk genotype. The presence of the risk allele seems to be related to the lack of visual improvement over one year of treatment with inhibitors of VEGF. These results suggest that the profile of the CFH genotype may present pharmacogenetic effect in this group of Brazilian patients, negatively influencing the response to treatment of exudative AMD with antiangiogenic drugs
Doutorado
Oftalmologia
Doutor em Ciências Médicas
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Lopes, Leticya Lerner. "Detecção do vírus da cinomose em cães naturalmente infectados no Mato Grosso." Universidade Federal de Mato Grosso, 2014. http://ri.ufmt.br/handle/1/535.
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CAPES
O vírus da cinomose canina (VCC) é um vírus RNA, que pertence ao gênero Morbillivírus e família Paramyxoviridae. A capacidade de resposta imune, assim como sua virulência são fatores críticos para a invasão viral dos tecidos epiteliais e do sistema nervoso central (SNC). O VCC é o maior responsável pelas encefalites em cães, acometendo diversas idades. O objetivo desse estudo foi detectar o VCC nos cães com sinais neurológicos encaminhados para necropsia no Laboratório de Patologia Veterinária da Universidade Federal de Mato Grosso (LPV-UFMT). Durante um período de um ano, 85% (68/80) dos cães necropsiados tinham lesões microscópicas compatíveis com encefalomielite causada pelo VCC. Desses, 67.6% (46/68) foram confirmadas positivas através da imuno-histoquímica (IHQ). Microscopicamente, as lesões do SNC foram classificadas em encefalite desmielinizante aguda em 15.2% (7/46) dos cães, em subaguda em 73.9% (34/46) e crônica em 10.8% (5/46) dos cães. O cerebelo foi principal órgão a apresentar marcação positiva na IHQ (97.8%). O VCC é responsável pelos sinais neurológicos em cães principalmente abaixo de um ano de idade. A cinomose demonstrou sua relevância dentro da população canina de Cuiabá, sendo necessário ao nosso entendimento, caracterizar a estirpe viral relacionada à região.
Canine distemper virus (CDV) is a RNA virus classified under the genus Morbillivirus within the family of Paramyxoviridae. The time of onset of the immune response and, likely, also the virulence of the virus are critical factors in the extent of viral invasion of epithelial tissues and of the central nervous system. The CDV is the most responsible of encephalitis in dogs from different ages. In this study, the aim was to detected CDV in dogs with neurologicals signs referred for necropsy at the Laboratory of Veterinary Pathology, Federal University of Mato Grosso (LPV-UFMT).Over a period of 1 year, 85% (68/80) of the dogs necropsied had microscopic lesions compatible encephalomyelitis by CDV. Which 67.6% (46/68) were confirmed by immunohistochemistry (IHC). Microscopically, the CNS lesions were classified demyelinating encephalitis in 15.2% (7/46) to acute, 73.9% (34/46) in subacute and 10.8% (5/46) to chronic. The cerebellum (97.8%) was the main target organ to verify positivity in the IHC. Canine distemper virus is a pathogen responsible for neurological clinical signs in dogs mainly under one year of age. Distemper demonstrated its relevance within the canine population of Cuiabá, being necessary to our understanding, characterizing the viral strain related to the region.
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Silva, Cicero Igor Simoes Moura. "Genótipos cagA , vacA e alelos e sítios de fosfolilação de tirosina da proteína caga do h. pylori em pacientes com e sem história familiar de câncer gástrico." reponame:Repositório Institucional da UFC, 2009. http://www.repositorio.ufc.br/handle/riufc/7298.
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SILVA, Cicero Igor Simoes Moura. Genótipos cagA , vacA e alelos e sítios de fosfolilação de tirosina da proteína caga do h. pylori em pacientes com e sem história familiar de câncer gástrico. 2009. 73 f. Dissertação (Mestrado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2009.Submitted by denise santos (denise.santos@ufc.br) on 2014-02-18T14:08:21Z No. of bitstreams: 1 2009_dis_cismsilva.pdf: 858659 bytes, checksum: d9ead253a62bca88b77a42f2664ed067 (MD5)
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The H. Pylori strains demonstrate a high level of phenotypic and genotypic diversity, the expression of various genes, which confer greater pathogenicity to the bacteria. Relatives of patients with gastric cancer have a higher risk of developing gastric diseases, especially if they are infected with more virulent strains of H. pylori. The objective was to characterize the strains of H. pylori, the presence of genes vacA, cagA, and sites of tyrosine phosphorylation of CagA protein - EPIYA in patients with and without family history of gastric cancer, and correlate the presence of the cagA gene to the level of activity and inflammation chronic gastritis. The genotyping of strains of H. pylori was performed by PCR and sequencing of the phosphorylation sites EPIYA. We evaluated 94 biopsy samples of gastric mucosa from dyspeptic patients H. pylori positive, 55 with a family history of gastric cancer and 39 without family history. All genotyped strains were vacA positive, and 45.7% with the vacA allele s1m1; s1m2 vacA 26.6%, 4.3% were vacA s2m1; 10.6% vacA s2m2; 3 hybrid strains and 9 (9.6 %) showed only the allele sequence signal (s). Of the 94 strains genotyped 87.2% were cagA positive, with no statistical difference between groups of familiar and unfamiliar (92.7% vs 82.0%, p = 0.058). The cagA gene was present in most patients with gastritis, with statistical significance in the group of relatives of cancer (p = 0.004). The degree of activity and inflammation of gastritis, was more significant in the group of patients with cagA positive strains, with pangastritis Corpal and gastritis. In the antrum, there were significant only in relation to the activity of gastritis. The studed strains, 93.9% showed EPIYA phosphorylation sites, with 59.2% of these had only one site, 38.2% with two sites and 2.6% with three sites. There was no statistical difference in the number of sites EPIYA between the groups. It is important to genetically characterize the strains of H. pylori to establish clearly its role in different clinical conditions related to it. Keywords: H. pylori.
Cepas de H. pylori demonstram um alto nível de diversidade fenotípica e genotípica, pela expressão de vários genes, que conferem maior patogenicidade à bactéria. Familiares de pacientes com câncer gástrico têm maior risco de desenvolver doenças gástricas, principalmente se forem infectados por cepas mais virulentas de H. pylori. O objetivo foi caracterizar as cepas de H. pylori, quanto à presença dos genes vacA, cagA e dos sítios de fosforilação de tirosina da proteína CagA – EPIYA, em pacientes com e sem história familiar de câncer gástrico, e correlacionar a presença do gene cagA com o grau de atividade e de inflamação da gastrite crônica. A genotipagem das cepas de H. pylori foi realizada através da técnica de PCR e do sequenciamento dos sítios de fosforilação EPIYA. Foram avaliados 94 fragmentos de biópsia de mucosa gástrica provenientes de pacientes dispépticos H. pylori positivo, 55 com história familiar de câncer gástrico e 39 sem historia familiar. Todas as cepas genotipadas foram vacA positivas, sendo 45,7% com o alelo vacA s1m1; 26,6% vacA s1m2; 4,3% eram vacA s2m1; 10,6% vacA s2m2; 3 cepas híbridas e 9 (9,6%) apresentaram somente o alelo da sequência sinal(s). Das 94 cepas genotipadas 87,2% foram cagA positivas, não havendo diferença estatística entre os grupos de familiares e não familiares (92,7% vs 82,0%; p= 0.058). O gene cagA estava presente na maioria dos pacientes portadores de gastrite, havendo significância estatística no grupo dos familiares de câncer (p= 0,004). O grau de atividade e inflamação da gastrite, foi mais significante no grupo de pacientes com cepas cagA positivo, com pangastrite e gastrite corpal. No antro, somente houve significância com relação à atividade da gastrite. Das cepas estudadas, 93,9% apresentaram sítios de fosforilação EPIYA, sendo que 59,2% destas apresentaram somente um sitio, 38,2% com dois sítios e 2,6% com três sítios. Não houve diferença estatística com relação ao número de sítios EPIYA, entre os grupos estudados. É importante a caracterização genética das cepas de H. pylori para se estabelecer com clareza o seu papel nos diversos quadros clínicos a ele relacionado.
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Aysin, Ferhunde. "Transformation Of Nicotiana Tabacum Plants With Na+/h+ Antiporter (atnhx1) Gene Isolated From Arabidopsis Thaliana For Evaluation Of Salt Tolerance." Master's thesis, METU, 2006. http://etd.lib.metu.edu.tr/upload/3/12608910/index.pdf.
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Large, membrane-bound vacuoles of plant cells are suitable organelles for the compartmentation of ions. These vacuoles contain Na+/H+ antiporters for movement of Na+ within the organelle in exchange for H+. They provide an efficient mechanism to prevent the occurance of detrimental outcomes of Na+ accumulation in the cytosol. Identification of AtNHX1 gene that confers resistance to salinity by expressing a Na+/H+ antiport pump facilitates the understanding of the salt stress tolerance mechanisms of plants.
The aim of the present study was to isolate and clone the Arabidopsis thaliana AtNHX1 coding sequence for transformation of Nicotiana tabacum plants via Agrobacterium tumefaciens mediated gene transfer. For this purpose, total RNA was isolated from Arabidopsis thaliana plants and cDNA synthesis was performed. AtNHX1 (1614bp) was amplified by using cDNA of Arabidopsis via specific primers. The amplified PCR product was verified by sequencing. AtNHX1 coding sequence was cloned into the plant transformation vector pCVB1 and 10 independent putative transgenic tobacco plants were obtained via Agrobacterium tumefaciens mediated gene transfer sysytem. Transfer of selected 8 putative transgenic plants to soil provided the regeneration of T1 seeds. Germination of the seeds under different salt treatments (0, 50, 100, 150, 200, 250 mM NaCl) was observed for evaluating the salt tolerance of transformed plants. The 82% and 60% of the transgenic T1 seeds were germinated on 150 mM NaCl and 200 mM NaCl containing media, respectively. In contrast the germination percentage of wild type tobacco seeds under 150 mM NaCl and 200 mM NaCl concentrations were 39% and 21%, respectively. The germination rate of the transgenic T1 seeds were significantly higher (p=0,001) when compared to the control seeds especially under high salt stress conditions (150 and 200 mM NaCl). Taken all together, our results demonstrated that the germination efficiencies and growth of the plants transformed with AtNHX1 were higher than the wild type tobacco plants under high salt concentrations.
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Li, Donghui. "Purification, characterization, gene cloning and sequence analysis of a novel NADP(H)-dependent type III alcohol dehydrogenase from Thermococcus AN1." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq24679.pdf.
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Lakshmanan, Nagarajan. "Molecular characterization and transcriptional regulation of GCV3, the Saccharomyces cerevisiae gene encoding the H-protein of the glycine cleavage system." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0006/NQ40297.pdf.
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BORTOLIN, MARIE-LINE. "Caracterisation du gene hote du petit arn nucleolaire u19. Implication des snoarn h/aca dans la pseudouridylation de l'arn ribosomique." Toulouse 3, 1999. http://www.theses.fr/1999TOU30252.
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Les differentes etapes de la biogenese des ribosomes font intervenir des facteurs en trans et notamment des petits arn nucleolaires (ou snoarn). Certains d'entre eux sont impliques dans les etapes de clivage du precurseur ribosomique, mais la majorite sont requis pour les modifications post-transcriptionnelles de ce dernier (essentiellement des methylations en 2-o-ribose et des pseudouridylations). Les snoarn sont pour la plupart exprimes a partir d'introns de genes hotes codant pour des proteines ribosomiques ou nucleolaires. Au cours de ma these, j'ai clone le snoarn u19 murin par rt-pcr et participe a l'analyse de sa structure secondaire par utilisation de sondes chimiques et enzymatiques. L'analyse de ce snoarn nous a permis de le classer parmi les membres d'une famille appelee famille de snoarn a boites h/aca. Par criblage de banques nous avons identifie l'adn complementaire correspondant a l'expression du gene hote de u19. L'analyse informatique de cette sequence n'a revele aucun cadre de lecture significatif, bien qu'il soit episse, polyadenyle, nucleaire et metaboliquement stable. C'est donc un arn non codant comme il avait deja ete decrit dans la litterature. Notre equipe a joue un role important dans l'implication de la famille des snoarn h/aca dans la formation des pseudouridines. Par des experiences de transfections transitoires de minigenes ribosomiques j'ai montre qu'il n'existe qu'aucune sequence consensus ni structure secondaire, sur le precurseur ribosomique, capable de recruter directement les enzymes responsables des modifications. Par la suite, notre equipe a etabli un modele impliquant un appariement entre le snoarn et le pre-arnr via des sequences complementaires. En cela, les snoarn jouent un role de guide dans la selection des uridines a convertir en pseudouridines. En combinant une etude de mutagenese systematique sur les snoarn h/aca et une technique specifique nous permettant de cartographier les nucleotides modifies (par modification chimique de l'arnr suivi d'une reverse transcription), j'ai montre que l'integrite de la structure secondaire des snoarn h/aca etait necessaire a la fonctionnalite de ces derniers. Notre equipe vient recemment de demontrer que d'autres types d'arn cellulaires peuvent etre le substrat de snoarn guides tel que le petit arn nucleaire u6 (pour les 2-o-methylations). Ces travaux suggerent que ce dernier pourrait transiter par le nucleole. A ce jour, seules quatre proteines specifiques des snoarn h/aca ont ete caracterisees. Aussi, afin de mieux apprehender les interactions arn-proteines mises en jeu dans ces complexes rnp nous avons adopte une approche d'immunoprecipitation chez s. Cerevisiae en testant systematiquement la capacite de chacune de ces quatre proteines a interagir avec diverses versions de snoarn h/aca mutantes. Ces etudes sont en cours.
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Lanning, Dennis Keith. "The H-2S/D region of the mouse major histocompatibility complex : Cosmid cloning, novel gene identification, and tissue expression studies /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487862399448473.
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Öberg, Daniel. "The Role of Polyadenylation in Human Papillomavirus Type 16 Late Gene Expression." Doctoral thesis, Uppsala University, Department of Medical Biochemistry and Microbiology, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4774.
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High-risk type human papillomaviruses (HPVs) are associated with cancer. HPVs are strictly epitheliotropic and infect basal cell layers, establishing a life cycle strongly linked to the differentiation stage of the infected cells. The viral capsid late genes, L2 and L1, are only expressed in terminally differentiated epithelium. Late gene expression involves regulation of most gene processing events including transcription, splicing, polyadenylation, mRNA stability and translation.
Both L2 and L1 have elements present in the open reading frames (ORFs) negatively affecting mRNA levels and translation. The negative elements in L1 were mapped to the first 514 nucleotides, with the strongest inhibitory effect located in the first 129 nucleotides. The negative elements in the L2 sequence were concentrated in two locations on the gene. Both genes were mutated by changing the nucleotide sequence while retaining the amino acid sequence. Mutating the first 514 nucleotides in L1 deactivated the negative elements while the entire L2 gene had to be mutated to achieve the same result. The L2 protein was found to localise the L1 protein into a punctuated pattern in the nucleus.
In the HPV-16 genome the negative elements reside in regions important for regulation of polyadenylation and splicing, critical for late gene expression. By exchanging parts of the L2 gene in subgenomic constructs with the corresponding mutant sequence we show that certain features of the L2 elements direct splicing to the L1 splice acceptor, and also regulate the efficiency of the early polyadenylation site. Cumulative binding of hnRNP H to the L2 mRNA gradually increased polyadenylation efficiency. Most interestingly, hnRNP H levels were downregulated in more differentiated epithelial cells.
Elucidation of how expression of the immunogenic late proteins is regulated would be greatly beneficial in prevention and treatment of HPV infection and thereby cancer.
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Rettschlag, Jeannine [Verfasser], P. [Gutachter] Persson, R. H. G. [Gutachter] Schwinger, and Roland [Gutachter] Willenbrock. "Linksventrikuläre Expression verschiedener Housekeeping-Gene bei kardialer Hypertrophie und Herzinsuffizienz / Jeannine Rettschlag ; Gutachter: P. Persson, R. H. G. Schwinger, Roland Willenbrock." Berlin : Humboldt-Universität zu Berlin, 2003. http://d-nb.info/1207665835/34.
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Nazarenko, Irina [Verfasser], Christian [Gutachter] Hagemeier, Reinhold [Gutachter] Schäfer, and Thomas [Gutachter] Börner. "Functional investigation of the class II tumor suppressor gene H-REV107-1 / Irina Nazarenko ; Gutachter: Christian Hagemeier, Reinhold Schäfer, Thomas Börner." Berlin : Humboldt-Universität zu Berlin, 2003. http://d-nb.info/1207672645/34.
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Flor, Matthias [Verfasser], Peter Akademischer Betreuer] Hammerstein, John H. [Akademischer Betreuer] Werren, and Edda [Akademischer Betreuer] [Klipp. "Unidirectional CI and the consequences of Wolbachia for gene flow and reinforcement / Matthias Flor. Gutachter: Peter Hammerstein ; John H. Werren ; Edda Klipp." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2011. http://d-nb.info/1015046525/34.
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Ellis, Tammy Lynn. "Modulation of apolipoprotein AI gene expression by oxidative stress, regulation by both the pro-oxidant H¦2O¦2 and the antioxidant DMSO." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq20631.pdf.
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Böhm, Volker [Verfasser], Niels H. [Akademischer Betreuer] Gehring, and Karin [Akademischer Betreuer] Schnetz. "Surveillance of mRNP composition during translation termination regulates gene expression via nonsense-mediated mRNA decay / Volker Böhm. Gutachter: Niels H. Gehring ; Karin Schnetz." Köln : Universitäts- und Stadtbibliothek Köln, 2015. http://d-nb.info/1075593182/34.
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Wijayanti, Nastiti. "Signaling pathways of heme oxygenase-1 gene activation by lipopolysaccharide and NAD(P)H oxidase inhibitor 4-(2-aminoethyl) benzensulfonyl fluorid in monocytes." Gießen : Fachverl. Köhler, 2005. http://geb.uni-giessen.de/geb/volltexte/2006/2651/index.html.
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Salmon, Anne-Marie. "Expression d'un gene hybride h-2k**(b)/hormone de croissance dans des souris transgeniques : stimulation specifique, dans les lymphocytes b et dans les hybridomes derives, par la sequence enhancer d'un gene de chaine lourde d'immunoglobulines." Paris 6, 1988. http://www.theses.fr/1988PA066526.
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Expression genique de gene hybrides h-2k**(b)/hgh ou enh-h-2k**(b)/hgh chez des souris transgeniques, specificite du tissu, stimulation dans les lymphocytes b et dans les transhybridomes obtenus de lymphocytes
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Rasch, Sebastian [Verfasser], Dieter K. M. [Akademischer Betreuer] Saur, and Jörg H. [Akademischer Betreuer] Kleeff. "Analyse der Metastasierung des Pankreaskarzinoms: Identifizierung differenziell exprimierter Gene / Sebastian Rasch. Gutachter: Jörg H. Kleeff ; Dieter K. M. Saur. Betreuer: Dieter K. M. Saur." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/104842877X/34.
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Vollmer, Marion [Verfasser], Wolfgang [Akademischer Betreuer] Wurst, and Kay H. [Akademischer Betreuer] Schneitz. "Die Identifizierung X-chromosomaler Gene mit Einfluss auf die Embryonalentwicklung und die Entstehung humaner Krankheiten / Marion Vollmer. Gutachter: Kay H. Schneitz. Betreuer: Wolfgang Wurst." München : Universitätsbibliothek der TU München, 2010. http://d-nb.info/1055916601/34.
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Kallassy-Awad, Mireille. "Étude de gènes impliqués dans la cancerogénèse de la peau chez l'homme : implications des gènes p21WAF1, ptch, smoh et cdc27HS/h-nuc." Lyon 1, 1998. http://www.theses.fr/1998LYO1T051.
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Xiao, Xue. "C3 glomerulopathy: exploring the role of the glomerular micro-environment in disease pathogenesis." Diss., University of Iowa, 2017. https://ir.uiowa.edu/etd/6019.
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C3 glomerulopathy (C3G) encompasses a group of severe renal diseases characterized by “dominant C3” deposition in the renal glomerulus. Patients typically present as nephritic nephrotics, with hematuria, hypertension, heavy proteinuria and edema. Within ten years of diagnosis, 50% of affected patients progress to end-stage renal disease and require dialysis or renal transplantation. No treatment is available to halt disease progression and thus both disease recurrence and allograft loss are common after transplantation.
Genetic studies of C3G have firmly implicated dysregulation of the alternative pathway (AP) of complement in disease pathogenesis. In addition to genetic factors, acquired factors like autoantibodies can also exaggerate AP activity in the circulation to cause C3G. Although AP dysregulation in the circulation (i.e. fluid-phase dysregulation) has been well studied in these patients, AP activity in the glomerular microenvironment is not well understood.
In this body of work, we used MaxGel, an ex-vivo surrogate for the glomerular extracellular matrix, to study AP activity and regulation. We showed that C3 convertase can be assembled on MaxGel and elucidated the dynamics of its formation and decay in the presence of complement regulators. We confirm that on MaxGel factor H (fH) inhibits C3 convertase formation and accelerates its decay, while properdin has a stabilizing effect. We also show that the complement factor H-related proteins (FHRs) are vital to the regulation of AP activity.
Consistent with our MaxGel data, CFHR gene-fusion events have been reported as genetic drivers of disease in a few familial cases of C3G. One such familial case in which we identified and characterized the rearrangement event results from a novel CFHR5-CFHR2 fusion gene. The fusion gene is translated into a circulating FHR-5/-2 protein that consists of the first two SCRs of FHR-5 followed by all four SCRs of FHR-2. The structural repetition of SCR1-2 followed by another SCR1-2 motif facilitates the formation of complex FHR-1, FHR-2 and FHR-5 multimers, which have enhanced affinity for C3b and by out-competing fH, lead to impaired C3 convertase regulation in the glomerular microenvironment.
Finally, we tested gene therapy as a tool to rescue the disease phenotype and restore fluid-phase AP complement control in a mouse model of C3G (Cfh-/-/huCR1-Tg mice). Using the piggyBac transposon system, we introduced a construct derived from complement regulator 1 (CR1) into Cfh-/-/huCR1-Tg mice. Delivery of sCR1-AC via hydrodynamic tail vein injection provided constitutive circulatory expression of sCR1-AC, and in animals followed for 6 months, we found that long-term expression of this complement regulator rescued the renal phenotype. These results suggest that sCR1 may be a potential therapy for patients with this disease.
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Zeng, Yan [Verfasser], H. [Gutachter] Lode, R. [Gutachter] Erttmann, and R. [Gutachter] Xiang. "T-cell mediated suppression of neuroblastoma following fractalkine gene therapy is amplified by targeted IL-2 / Yan Zeng ; Gutachter: H. Lode, R. Erttmann, R. Xiang." Berlin : Humboldt-Universität zu Berlin, 2006. http://d-nb.info/1208077031/34.
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Jernerén, Fredrik. "Novel Fatty Acid Dioxygenases of Human and Plant Pathogenic Fungi : Studies by Gene Deletion and Expression." Doctoral thesis, Uppsala universitet, Institutionen för farmaceutisk biovetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-143065.
Full textAbstract:
The dioxygenase-cytochrome P450 fusion proteins (DOX-CYP) comprise a heme-containing enzyme family that shares structural and catalytic properties with mammalian prostaglandin H (PGH) synthases. 7,8-Linoleate diol synthase (7,8-LDS) of Gaeumannomyces graminis was first characterized, and DOX-CYP enzymes are of mechanistic and biological interest. The growing number of fungal genome sequences has revealed DOX-CYP homologues in medically and economically important species. The aim of this thesis was to identify novel members of the DOX-CYP fusion protein family. The devastating rice pathogen Magnaporthe oryzae contains two DOX-CYP genes. The fungus synthesizes 7S,8S-dihydroxyoctadecadienoic acid (7,8-DiHODE) by dioxygenation of linoleic acid to 8R-hydroperoxyoctadecadienoic acid (8R-HPODE), and subsequent isomerisation to the diol. 7,8-LDS of M. oryzae was identified by gene deletion, but the infection and reproduction processes of the Δ7,8-LDS strain were not altered. A mutant with constitutive protein kinase A activity profoundly changed the oxygenation profile, possibly due to post-translational modification. The human pathogens Aspergillus fumigatus and A. clavatus contain three DOX-CYP, designated psi producing oxygenase A (ppoA), ppoB, and ppoC, and form three oxylipins: 5S,8R-DiHODE, 8R,11S-DiHODE, and 10R-hydroxyoctadecadienoic acid. PpoA was identified as 5,8-LDS, and ppoC as 10R-DOX. The 8,11-linoleate hydroperoxide isomerase activity was reduced by two imidazole-containing P450 inhibitors, miconazole and 1-benzylimidazole. PpoB could not be linked to the biosynthesis of 8,11-DiHODE for the following reasons: First, the 8,11-hydroperoxide isomerase activity was retained in A. fumigatus ΔppoB strains. Second, the P450 domain of the deduced ppoB of A. clavatus lacks a heme-thiolate cysteine ligand, presumably essential for hydroperoxide isomerase activity. Linoleate 9R-DOX activities of Aspergillus terreus and Lasiodiplodia theobromae were discovered. 9R-HPODE was further converted into unstable allene oxides, as judged by the accumulation of their hydrolysis products, α- and γ-ketols. These allene oxide synthase activities were specific for 9R-hydroperoxides. The 9R-DOX and AOS were found to have unique characteristics. In conclusion, novel DOX-CYP enzymes were identified in human and plant pathogenic fungi. These enzymes might be involved in biological processes, and show interesting catalytic similarities to human PGH synthase and thromboxane synthase (CYP5A).
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Wijayanti, Nastiti [Verfasser]. "Signaling pathways of heme oxygenase-1 gene activation by lipopolysaccharide and NAD(P)H oxidase inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride in monocytes / vorgelegt von Nastiti Wijayanti." Gießen : Fachverl. Köhler, 2006. http://d-nb.info/978882415/34.
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