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Schumacher, Fredrick Ray. "Relation between the selenoprotein gene, selenium and prostate cancer." Connect to text online, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1132766716.
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Thesis (Ph. D.)--Case Western Reserve University, 2006.[School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.
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Schumacher, Fredrick R. "Relation Between the Selenoprotein Gene, Selenium, and Prostate Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=case1132766716.
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Roberts, Joanna Elizabeth. "Establishment and microbial activity in relation to gene transfer in soil." Thesis, University of Exeter, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.296624.
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Beyzade, Seyyare. "Variation in the matrix metalloproteinase-3 gene in relation to atherosclerosis." Thesis, University of Southampton, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273898.
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Otwe, Emmanuel Plas. "Genetic diversity, candidate genes and gene expression in relation to drought tolerance in Ghanaian cowpeas (Vigna unguiculata)." Thesis, University of Leicester, 2007. http://hdl.handle.net/2381/29740.
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Cowpea (Vigna unguiculata) is grown mainly for its protein-rich grains, which are consumed in various forms in sub-Saharan Africa. The initial phase of the study was the screening of the germplasm for drought tolerance. One hundred and six cowpea accessions from Ghana were evaluated for seedling drought tolerance on an individual plant basis under greenhouse conditions using the pot screening method. The results suggested that there were more drought tolerance accessions in the germplasm than the susceptible ones. They cluster results from the morphological analysis were informative but inadequate to effectively determine variability of germplasm. DNA-based techniques are essential to assay the variation present in wild and cultivated populations of crops both to ensure breeders have the full range of diversity for assessment and application, and to prevent loss of diversity for future farmers. Three multi-locus PCR based molecular markers; SSR (simple, sequence, repeat), IRAP (inter-retrotransposon amplified polymorphism) and REMAP (retrotransposon---microsatellite amplified polymorphisms) were used for the diversity analysis. The results indicated the highly polymorphic nature of the DNA markers used; small groups could be used to identify each of the accessions and the diversity recorded by each marker showed good correlation coefficient values. The results from the cluster analysis could be used as basis for planning crosses of the lines for further analysis. The fragment candidate gene cloning and sequencing analysis indicated the enormous diversity amongst the accessions. Numerous SNPs were identified in both exonic and intronic regions as well as some deletions and insertions. The SNPs were largely nucleotide transitional in character and comparative analysis with other plant species indicated that some correlated with previously identified gene and polymorphisms related to drought stress. The study also identified many abiotic or drought inducible genes in cowpea from the differential display PCR (DD-PCR) analysis. Different conditions induced different stress-inducible genes and thus there must be several different signalling mechanisms that are important for future identification and analysis.
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MARLIN, SANDRINE. "Surdites hereditaires humaines : genotypes et phenotypes en relation avec les mutations du gene sall1 et du gene cx26." Paris 6, 1999. http://www.theses.fr/1999PA066326.
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Les surdites dites syndromiques (deficit auditif associe a d'autres signes cliniques) representent un tiers des surdites hereditaires de l'enfant. Le syndrome de townes-brocks, caracterise par des malformations des 3 compartiments de l'oreille, de l'anus et des extremites des membres, se transmet sur un mode autosomique dominant. La localisation chromosomique, en 16q12. 1, du gene responsable, a ete definie par la translocation reciproque t(5;16)(q15. 3;q12. 1) chez une patiente affectee par ce syndrome. Ce gene, sall1, est l'orthologue du gene de developpement spalt de la drosophile, qui code pour un facteur de transcription. La caracterisation de la region chromosomique contenant le point de cassure de la patiente porteuse de la translocation reciproque t(5;16)(q15. 3;q12), que nous avions entreprise afin d'isoler le gene responsable par clonage positionel, nous a permis de localiser sall1 a au moins 180 kb du point de translocation, suggerant qu'un effet de position est a l'origine du syndrome chez cette patiente. L'analyse de sall1 a ete effectuee chez 11 patients et a conduit a l'identification d'une mutation chez 9 d'entre eux. Toutes les mutations creent un arret premature de la traduction, indiquant que la survenue de ce syndrome est due a une haploinsuffisance. Un fort taux de neo-mutations (4/9), une penetrance complete et une expressivite variable de la maladie ont ete observes. Le gene codant pour la connexine 26, cx26, est responsable d'une surdite neurosensorielle non syndromique, de transmission autosomique recessive. Notre but etait de determiner la prevalence des mutations de ce gene parmi les surdites de l'enfant et de definir finement le phenotype correspondant. Nous avons d'abord recherche des mutations dans cx26 chez 65 familles presentant une surdite severe ou profonde de transmission autosomique recessive. Une mutation a ete identifiee chez 49% des patients et une deletion, 30delg, representait a elle seule 69% des alleles mutes. Une seconde etude, prospective, a ete menee sur 140 patients suivis a la consultation de conseil genetique des surdites dont j'ai la charge. L'implication de cx26 a ete trouvee dans 56% des cas de cette forme de surdite et dans 43% des cas sporadiques. Enfin, nous avons defini le phenotype lie aux mutations de ce gene : surdite prelinguale, de severite variable, y compris a l'interieur d'une meme famille, de faible evolutivite, sans malformation de l'oreille interne, ni trouble vestibulaire.
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Hasan, Mohammad Shabbir. "Investigating Gene Relationships in Microarray Expressions: Approaches Using Clustering Algorithms." University of Akron / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=akron1376536496.
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Jarman, Andrew Paul. "Structural features of the human globin gene complexes and their relation to function." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279917.
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Cooper, Jessica E. "The horizontal and vertical evolution of Staphylococcus aureus in relation to gene function." Thesis, University of Bath, 2005. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419345.
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Kvaskoff, Marina. "Endometriosis and naevus-associated gene variants in relation to risk of cutaneous melanoma." Paris 11, 2009. http://www.theses.fr/2009PA11T090.
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Gnosa, Sebastian. "Astrocyte elevated gene-1 in relation to colorectal cancer development and radiotherapy response." Doctoral thesis, Linköpings universitet, Avdelningen för kliniska vetenskaper, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-121868.
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The incidence and death rate for colorectal cancer (CRC) decreased during the last decades as a result of improved diagnosis and treatment. However, CRC is still the third most common cancer in the world, and is responsible for about 700 000 deaths per year worldwide. Therefore, it is important to understand the mechanisms of the disease, and to find molecular markers in order to further improve prognosis, and to develop new treatment strategies. Astrocyte elevated gene-1 (AEG-1), encoded by the MTDH gene, is upregulated in a variety of cancers. AEG-1 is involved in cell survival, proliferation, migration, invasion, metastasis, angiogenesis, and apoptosis. The aim of this thesis was to investigate the role of AEG-1 in CRC development and the impact of AEG-1 on the response of radiation treatment. The AEG-1 expression, analysed in different CRC patient cohorts in paper I and III, was increased in the tumour tissue compared with the normal mucosa, and higher in the lymph node and liver metastases. Expression analyses in normal and cancer cell lines confirmed these results. In paper II, sequencing of the complete coding sequence of the MTDH gene in 356 patients revealed 50 single nucleotide variants of which 29 were novel. Eight exonic variants were detected, including three frameshift variants which were probably pathogenic, and two missense variants located in functional protein regions. There was no correlation of the MTDH variants or AEG-1 expression with the patient survival. In paper III, we also investigated the impact of AEG-1 on the response to radiation treatment. AEG-1 knockdown decreased the cellular survival upon radiation in several colon cancer cell lines. The AEG-1 expression was furthermore analysed in patients, which were randomised to either surgery alone or preoperative radiotherapy (RT), followed by surgery. The rectal cancer patients with high AEG-1 expression treated with RT had a significantly higher risk of developing distant recurrence and had a worse disease free survival, likely due to the metastasis promoting properties of AEG-1. In paper IV, the impact of AEG-1 knockdown and radiation on migration and invasion was analysed in colon cancer cell lines in vitro and in a novel zebrafish model in vivo. AEG-1 knockdown decreased migration and invasion, and radiation-enhanced migration and invasion in the cell lines tested. In conclusion, our data suggest that AEG-1 is involved in CRC development, while MTDH gene variants probably not have a high clinical importance in CRC. Furthermore, AEG-1 is a promising radiosensitising target and a valuable prognostic marker in CRC. We further showed that AEG-1 knockdown inhibits migration and invasion, as well as radiation-enhanced cell migration and invasion.
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Zhang, Baiping. "Study of the regulation of expression and activity of gelatinase B in relation to the development of atherosclerosis." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342587.
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Axtner, Jan. "Immune gene expression and diversity in relation to gastrointestinal parasite burden in small mammals." Phd thesis, Universität Potsdam, 2012. http://opus.kobv.de/ubp/volltexte/2013/6563/.
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MHC genes encode proteins that are responsible for the recognition of foreign antigens and the triggering of a subsequent, adequate immune response of the organism. Thus they hold a key position in the immune system of vertebrates. It is believed that the extraordinary genetic diversity of MHC genes is shaped by adaptive selectional processes in response to the reoccurring adaptations of parasites and pathogens. A large number of MHC studies were performed in a wide range of wildlife species aiming to understand the role of immune gene diversity in parasite resistance under natural selection conditions. Methodically, most of this work with very few exceptions has focussed only upon the structural, i.e. sequence diversity of regions responsible for antigen binding and presentation. Most of these studies found evidence that MHC gene variation did indeed underlie adaptive processes and that an individual’s allelic diversity explains parasite and pathogen resistance to a large extent. Nevertheless, our understanding of the effective mechanisms is incomplete.
A neglected, but potentially highly relevant component concerns the transcriptional differences of MHC alleles. Indeed, differences in the expression levels MHC alleles and their potential functional importance have remained unstudied. The idea that also transcriptional differences might play an important role relies on the fact that lower MHC gene expression is tantamount with reduced induction of CD4+ T helper cells and thus with a reduced immune response. Hence, I studied the expression of MHC genes and of immune regulative cytokines as additional factors to reveal the functional importance of MHC diversity in two free-ranging rodent species (Delomys sublineatus, Apodemus flavicollis) in association with their gastrointestinal helminths under natural selection conditions.
I established the method of relative quantification of mRNA on liver and spleen samples of both species in our laboratory. As there was no available information on nucleic sequences of potential reference genes in both species, PCR primer systems that were established in laboratory mice have to be tested and adapted for both non-model organisms. In the due course, sets of stable reference genes for both species were found and thus the preconditions for reliable measurements of mRNA levels established.
For D. sublineatus it could be demonstrated that helminth infection elicits aspects of a typical Th2 immune response. Whereas mRNA levels of the cytokine interleukin Il4 increased with infection intensity by strongyle nematodes neither MHC nor cytokine expression played a significant role in D. sublineatus.
For A. flavicollis I found a negative association between the parasitic nematode Heligmosomoides polygyrus and hepatic MHC mRNA levels. As a lower MHC expression entails a lower immune response, this could be evidence for an immune evasive strategy of the nematode, as it has been suggested for many micro-parasites. This implies that H. polygyrus is capable to interfere actively with the MHC transcription. Indeed, this parasite species has long been suspected to be immunosuppressive, e.g. by induction of regulatory T-helper cells that respond with a higher interleukin Il10 and tumor necrosis factor Tgfb production. Both cytokines in turn cause an abated MHC expression. By disabling recognition by the MHC molecule H. polygyrus might be able to prevent an activation of the immune system. Indeed, I found a strong tendency in animals carrying the allele Apfl-DRB*23 to have an increased infection intensity with H. polygyrus. Furthermore, I found positive and negative associations between specific MHC alleles and other helminth species, as well as typical signs of positive selection acting on the nucleic sequences of the MHC. The latter was evident by an elevated rate of non-synonymous to synonymous substitutions in the MHC sequences of exon 2 encoding the functionally important antigen binding sites whereas the first and third exons of the MHC DRB gene were highly conserved.
In conclusion, the studies in this thesis demonstrate that valid procedures to quantify expression of immune relevant genes are also feasible in non-model wildlife organisms. In addition to structural MHC diversity, also MHC gene expression should be considered to obtain a more complete picture on host-pathogen coevolutionary selection processes. This is especially true if parasites are able to interfere with systemic MHC expression. In this case advantageous or disadvantageous effects of allelic binding motifs are abated. The studies could not define the role of MHC gene expression in antagonistic coevolution as such but the results suggest that it depends strongly on the specific parasite species that is involved.Die Hauptaufgabe von MHC-kodierten Proteinen ist die Erkennung von körperfremden Molekülen sowie das Einleiten einer adäquaten Immunantwort, womit sie eine Schlüsselrolle im Immunsystem der Wirbeltiere einnehmen. Man nimmt an, dass ihre außergewöhnliche Vielfalt eine Antwort auf die sich ständig anpassenden Parasiten und Krankheitserreger ist, durch adaptive Selektion erhalten wird und dass die individuelle Allelausstattung einen Großteil der Parasitenbelastung erklärt, wofür bereits zahlreiche MHC-Studien Hinweise gefunden haben. Trotzdem ist unser Verständnis über die wirkenden Mechanismen teilweise noch lückenhaft. Ein stark vernachlässigter Aspekt hierbei sind z.B. eventuelle Unterschiede in der Genexpression der MHC-Allele und eine geringere Expression wäre gleichbedeutend mit einer geringeren Aktivierung des Immunsystems. Ich habe hierzu zwei frei lebende Kleinsäugerarten (Delomys sublineatus, Apodemus flavicollis) unter natürlichen Selektionsbedingungen untersucht. Dabei habe ich neben der genotypischen Diversität von MHC-Genen auch deren Expression, sowie die Genexpression immunregulativer Zytokine mit in Betracht gezogen und in Relation zur individuellen Belastung mit gastrointestinalen Helminthen gesetzt. Anhand von Leber und Milzproben beider Arten habe ich die Methode der ‚real-time PCR‘ zur relativen Quantifizierung von mRNA im Labor etabliert. Bereits für die Labormaus etablierte PCR-Primersysteme wurden an beiden Arten getestet und so konnten stabile Referenzgene gefunden werden, die Grundvoraussetzung für zuverlässige Genexpressionsmessungen. Für D. sublineatus konnte gezeigt werden, dass Helminthenbefall eine typische Th2 Immunantwort induziert, und dass der Zytokin Il4 Gehalt mit Befallsintensität strongyler Nematoden zunimmt. Es wurde für D. sublineatus kein signifikanter Zusammenhang zwischen MHC Expression oder anderen Zytokinen mit Helminthenbefall gefunden. In A. flavicollis wurde ein negativer Zusammenhang zwischen haptischer MHC-Expression und dem parasitären Nematoden Heligmosomoides polygyrus festgestellt, was auf eine Immunvermeidungsstrategie des Nematoden hindeutet. Ich fand typische positive und negative Assoziationen zwischen MHC-Allelen und anderen Helminthenarten, sowie Zeichen eines positiven Selektionsdruckes auf den MHC-Sequenzen, was sich durch eine erhöhte Rate aminosäureverändernder Mutationen zeigte. Diese nicht-synonymen Veränderungen waren auf Positionen innerhalb des zweiten Exons des DRB-Genes beschränkt, wohingegen die untersuchten Bereiche des ersten und dritten Exons stark konserviert vorlagen. Diese variablen Positionen kodieren Schlüsselstellen im Bereich der Antigenbindungsstelle im MHC Molekül. Zusammenfassend zeigt diese Arbeit, dass Genexpressionsstudien auch an Wildtieren durchgeführt und verlässliche Daten erzeugt werden können. Zusätzlich zur strukturellen Vielfalt sollten zukünftig auch mögliche Genexpressionsunterschiede bei MHC-Studien berücksichtigt werden, um ein kompletteres Bild der koevolutiven Wirt-Parasiten-Beziehungen zeichnen zu können. Dies ist vor allem dann von evolutiver Bedeutung, wenn die Parasiten in der Lage sind die MHC Expression aktiv zu beeinflussen. Die Studien konnten nicht die exakte Bedeutung von MHC-Genexpression in der antagonistischen Koevolution definieren, aber sie konnten zeigen dass diese Bedeutung stark von den jeweils beteiligten Partnern abzuhängen vermag.
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Moawad, H. A. "Masseter muscle gene expression in relation to various craniofacial deformities : a genotype-phenotype study." Thesis, University College London (University of London), 2009. http://discovery.ucl.ac.uk/19032/.
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Craniofacial form is defined by a number of factors. A major contributor is the jaw musculature especially of the masseter muscle, as differences in transcription and translation of various genes have been documented from this tissue. Up to this point however, no reliable biological predictors of form have been identified. The aims of this study were therefore, to describe the transcriptome of the masseter muscle using microarray technology and to establish and correlate the expression levels of potential candidate and known “informative” genes in masseter muscle with selected clinical, radiographic and dental features of subjects with a variety of craniofacial morphologies. A total of 29 patients (18 deformity and 11 control) were selected from the orthodontic/orthognathic clinics at the Eastman Dental and Whipps Cross Hospitals, London, and Riyadh Military Hospital, Saudi Arabia. Microarray results indicated five “novel” genes not previously reported in relation to the masseter muscles of subjects with variable craniofacial morphologies. Two genes (KIAA1671 and DGCR6) were down-regulated in long face patients, one (SERGEF) was down-regulated in Class III patients and one (LOC730245) was up-regulated in Class II long faces and in all Class III subjects, compared to controls. Another gene (NDRG2) was down-regulated in Class II compared to Class III individuals. Subsequent quantitative Reverse Transcriptase PCR results strongly confirmed that the “novel” gene SERGEF was down-regulated in relation to the clinical, dental and radiographic features of subjects with Class III appearance. SERGEF gene had a positive relationship to the number of dental occlusal contacts and ANB angle. The “informative” gene MHC7 was strongly related to both vertical and horizontal facial deformities. These data suggest that the expression profiles of a number of genes can be analysed and used to make assessments as to their role in the primary aetiology and successful or unsuccessful treatment of patients with specific craniofacial morphologies.
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Eva, Klimcakova. "Regulation of human adipose tissue gene expression in relation to obesity and insulin resistance." Toulouse 3, 2007. http://thesesups.ups-tlse.fr/40/.
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Parmi les mécanismes possibles de l'insulinorésistance associée à l'obésité figurent une altération de la production d'adipokines par le tissu adipeux (TA). Dans une première partie, nous avons étudié des patients obèses soumis à des programmes nutritionnels ou d'activité physique. Les données phénotypiques ont été reliées à l'expression de gènes du TA potentiellement impliqués dans la sensibilité à l'insuline. Nous avons confirmé qu'un entraînement en condition aérobie ou en force améliorait la sensibilité à l'insuline et démontré que ces interventions ne modifiaient pas l'expression génique dans le TA sous-cutané ou les niveaux plasmatiques d'adiponectine, d'interleukine 6, d'interleukine 1 beta et de tumor necrosis factor alpha mais diminuaient les concentrations circulantes de leptine. Différentes phases d'un programme de perte de poids améliorent la sensibilité à l'insuline et diminuent transitoirement les concentrations plasmatiques de la protéine de liaison du rétinol RBP4. Les niveaux d'ARNm ne sont diminués qu'après la première phase à très basses calories. Nos résultats montrent que les adipokines, excepté peut-être la leptine, ne semblent pas des médiateurs des changements d'insulinosensibilité induits par une intervention diététique ou l'exercice physique. Dans une seconde partie, nous avons exploré le rôle des PPARs (peroxysome proliferator-activated receptors) sur la sécrétion de protéines par le TA sous-cutané humain. Il apparaît que les PPARs régulent la production de facteurs sécrétés provenant de différents types cellulaires du TA. Cet ensemble d'études contribuent à notre compréhension des relations entre adipokines et sensibilité à l'insulineObesity is associated with insulin resistance (IR) and type 2 diabetes mellitus. Among possible mechanisms leading to IR are increased plasma levels of free fatty acids and altered levels of adipokines secreted from adipose tissue (AT). In the first part of the work, we studied obese patients during different nutritional and physical activity interventions. Phenotypic data were related to the expression of AT genes potentially involved in the regulation of insulin sensitivity (IS) and/or low-grade inflammation. We confirmed that aerobic and dynamic strength training improved IS and demonstrated that these interventions do not promote changes in subcutaneous AT gene expression or in plasma levels of adiponectin, interleukin-6, interleukin-1 beta and tumor necrosis factor-alpha, but decrease circulating leptin level. Very low calorie diet followed by low calorie diet and weight maintenance period enhanced IS in obese women and diminished retinol-binding protein 4 (RBP4) in plasma, but RBP4 mRNA levels were reduced only after very low calorie diet. Our findings indicate that the investigated adipokines, except potentially leptin, might not be mediators of changes in IS induced by lifestyle interventions. In the second part of the work, we investigated the role of peroxisome proliferator-activated receptors (PPARs) on the protein secretion by human subcutaneous AT. .
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Barton, Amanda Jane Lavini. "Studies of gene expression in the central nervous system in relation to Alzheimer's disease." Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46665.
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He, Feng, and 贺峰. "Detection of parent-of-origin effects and association in relation to aquantitative trait." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B44921408.
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Nopp, Anna. "Characterisation of eosinophil activity markers : relation to allergic inflammation and apoptosis /." Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-129-2.
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Amini, Nekoo Ali. "Molecular analysis of human tissue factor pathway inhibitor (TFPI) gene in relation to venous thrombosis." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427717.
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Ajlouni, Burouj Kayed. "Polymorphisms in the Flt1 gene and their relation to expression of the secreted Flt1 variant." Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/29426.
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Vascular endothelial growth factor (VEGF) is a potent angiogenic agent. VEGF activates its biologic responses through two cell-surface receptors, Flt1 and Flk1. In addition to the transmembrane form of Flt1, the Flt1 gene also encodes a secreted, truncated form of the receptor (sFlt1) translated from an mRNA in which a portion of intron 13 is preserved. sFlt1 retains high affinity for VEGF and thereby inhibits its
angiogenic activity. Intron 13 contains important cis elements involved in sFlt1 mRNA formation. Here, we test the hypothesis that polymorphisms in the human Flt1 gene, particularly SNPs at sites suspected to contain splicing or cleavage-polyadenylation
signals, influence Flt1 pre-mRNA processing and rates of Flt1 and sFlt1 expression. The NCBI SNP database contained 23 SNPs in the region of interest, one each in exons 13 and 14. An independent human SNP screen confirmed several of the reported SNPs. The web-based ESEfinder software predicted that the exon 13/14 SNPs had reduced potential for recruitment of splicing components. To test effects of exonic SNPs
on Flt1 pre-mRNA processing, wild type and mutant Flt1 minigene plasmids were transfected into NIH/3T3 cells. Both exonic SNPs were associated with ~40% decreases in Flt1:sFlt1 mRNA ratios determined by real-time PCR. To facilitate
exploration of ESEs in regulated RNA splicing, a PERL computer program, â EXONerator,â was written to silence predicted ESEs without altering polypeptide sequence. These results support the notion that small changes in exon composition can
have significant effects on splicing activity and underscore the utility of software tools for hypothesis generation.Ph. D.
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Lundholm, Lovisa. "Molecular mechanisms of estrogen action in relation to metabolic disease /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-392-4/.
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Lundberg, Anna. "Immune responses to lipopolysaccharide in relation to allergic disease : a TLR4 gene polymorphism and endotoxin exposure." Doctoral thesis, Linköpings universitet, Pediatrik, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-16783.
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Background: Allergic diseases have increased during the last decades, particularly in affluent countries, possibly due to a reduced and/or altered microbial exposure during infancy. Activation of the immune system by microbes early in life is probably required for accurate maturation of the immune system and tolerance development. It is not fully understood how microbial exposure is associated with the development of allergic diseases, however. Genetic factors may influence microbial induced immune responses. A certain polymorphism, in the gene coding for the Toll-like receptor 4, i.e. (TLR4 Asp299Gly), has been suggested to alter the immunological responsiveness to bacterial lipopolysaccharide (LPS). Aim: The aim of this thesis was to study the interplay between LPS induced immune responses, LPS signalling related genetic polymorphisms, allergic disease and endotoxin exposure. Subjects: The thesis is based on the results obtained from individuals in three different study groups, i.e. Estonian and Swedish children followed prospectively from birth up to five years of age, Swedish school-children eight and 14 years of age and young adults. Methods: The study subjects were clinically evaluated regarding allergic diseases with skin prick tests, circulating IgE levels, validated questionnaires and clinical examinations by paediatricians or research nurses. The gene polymorphisms TLR4 Asp299Gly and CD14/-159 were analysed. Peripheral blood mononuclear cells were isolated from blood and cultured with LPS from two Gram negative bacterial strains, i.e. Salmonella enterica serotype Typhimurium (Serotype Typhimurium) and Escherichia coli (E. coli). Cytokine and chemokine secretions were analysed with Luminex or ELISA technique. Receptor expression of circulating peripheral blood monocytes was analysed with flow cytometry. The phosphorylation of intracellular proteins involved in LPS signalling pathways was analysed with Luminex technique. mRNA expression of proteins involved in LPS signalling pathways and of markers for T regulatory cells were analysed with realtime-PCR. Results: In school-children and young adults, the TLR4 Asp299Gly gene polymorphism was associated with reduced LPS induced IκBα phosphorylation, IL-10 and IL-12 cytokine secretion. Interestingly, these findings were observed only when the cells were cultured with LPS from Serotype Typhimurium but not with LPS from E. coli. The polymorphism was positively associated with asthma, especially atopic asthma. Several differences in immunological responses to LPS were observed between allergic and non-allergic individuals. Asthma in school-children was associated with reduced LPS induced cytokine production of IL-10 and IL-12. The phosphorylation of IκBα was lower in adult allergic compared to non-allergic individuals. Swedish children who had developed allergic disease at five years of age had lower TLR2 mRNA expression at birth compared to children who remained healthy. Estonian children displayed generally lower LPS induced cytokine and chemokine production as compared to Swedish children both at birth and at 3 and 6 months of age. The mRNA expression of the T regulatory associated markers Foxp3 and Ebi3 were higher in the Estonian compared to the Swedish children at birth. Conclusion: Polymorphisms in genes coding for pattern recognition receptors can alter the immune responsiveness of the host to microbial components and may be of importance for the development of asthma. Lower LPS induced cytokine response and higher expression of T regulatory associated markers were seen in children from Estonia as compared to Sweden, suggesting an increased capacity for early immune regulation among infants from a country with a low prevalence of allergic disease.Bakgrund: Under de senaste decennierna har förekomsten av allergiska sjukdomar ökat i västvärlden. En av möjliga förklaringar kan vara en minskad eller förändrad mikrobiell exponering under uppväxttiden. Mikrobiella stimuli under de första levnadsåren tros vara viktiga för utmognaden av immunsystemet och utveckling av tolerans. Exakt hur mikroorganismers påverkan på immunförsvaret är kopplat till utvecklingen av allergiska sjukdomar är dock ännu okänt. Genetiska polymorfier kan påverka immunsvar mot mikrobiella komponenter. En sådan polymorfi, TLR4 Asp299Gly, har observerats i genen som kodar för receptorn TLR4 som känner igen lipopolysackarid (LPS) från Gramnegativa bakteriers cellvägg, och har föreslagits vara associerad med en förändrad förmåga att svara immunologiskt mot LPS. Syfte: Syftet med studierna var att studera immunsvar mot LPS i relation till specifika genetiska polymorfier, allergisk sjukdom samt mikrobiellt tryck i form av endotoxinnivåer. Studiepopulationer: Denna avhandling baseras på resultat från tre studiegrupper: estniska och svenska barn som är följda från födseln upp till fem års ålder, en grupp svenska skolbarn 8 och 14 år gamla samt en grupp unga vuxna. Metoder: Två genetiska polymorfier, TLR4 Asp299Gly och CD14/-159, analyserades. Mononukleära celler isolerades från perifert blod och odlades tillsammans med LPS från två olika Gramnegativa bakteriestammar, Salmonella enterica serotype Typhimurium (Serotype Typhimurium) och Escherichia coli ( E. coli). Cytokin- och kemokinsekretion analyserades i cellsupernatanter med Luminex eller ELISA. Ytmarkörer på monocyter i helblod studerades med flödescytometri. Intracellulära signaleringsproteiner, som är inblandade i TLR4s signalvägar analyserades med Luminexteknik. mRNA uttryck av proteiner som är relaterade till LPS signalering och markörer för regulatoriska T celler analyserades med realtids-PCR. Resultat: TLR4 Asp299Gly polymorfin var associerad med lägre fosforylering av det intracellulära signaleringsproteinet IκBα och lägre utsöndring av cytokinerna IL-12 och IL-10 efter cellstimulering med LPS hos skolbarn och unga vuxna. Skillnader i cellsvar mellan individer med och utan polymorfin kunde påvisas när cellerna odlats med LPS från Serotype Typhimurium men inte med LPS från E. coli. Polymorfin var också associerad med astma och särskilt atopisk astma. Flera skillnader i immunsvar mot LPS observerades mellan allergiska och ickeallergiska individer. Skolbarn med astma hade lägre LPS inducerad IL-10 och IL-12 cytokinproduktion. Vuxna allergiker hade lägre LPS inducerad IκBα fosforylering. Svenska barn som vid fem års ålder hade utvecklat allergisk sjukdom hade lägre mRNA uttryck av TLR2 vid födseln. Estniska barn hade generellt lägre LPS inducerade cytokinsvar än svenska barn vid födseln och vid 3 och 6 månaders ålder. mRNA uttrycket av de T-regulatoriskt associerade markörerna Foxp3 och Ebi3 var vid födseln högre hos de estniska jämfört med de svenska barnen. Slutsats: Genetiska förutsättningar kan påverka immunsvar mot LPS och kan möjligen ha en betydelse för utveckling av astma. De generellt lägre LPS inducerade cytokinsvaren och högre uttryck av markörer för Treg celler hos estniska jämfört med svenska barn skulle kunna bero på att deras uppväxtmiljö med ett högre mikrobiellt tryck påverkar den tidiga utvecklingen av immunförsvaret och kan möjligen vara en bidragande förklaring till den lägre allergifrekvens som ses i Estland jämfört med Sverige.
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Österlund, Marie. "Estrogen receptor gene activity within the brain and the relation to psychiatric disorders : mapping and function /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3867-9/.
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Zwolinski, Simon Andrew. "Gene conversion at the wI locus of Ascobolus immersus : characteristics, controls and relation to crossing-over." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47324.
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Heidari, Shirin. "Studies on persistent polyomavirus infection in relation to tumor development and options for vaccine and gene therapy /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4844-5/.
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Leander, Karin. "Family history in relation to myocardial infarction, and analyses of gene-environment interactions involving factors of haemostasis /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-396-5/.
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Prothero, Joanna. "Matrix metalloproteinase-3 (stromelysin-1) gene promoter polymorphism in relation to predisposition to inflammatory bowel disease (IBD)." Thesis, University of Southampton, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436934.
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CORBEX, MARILYS. "Etude de la variabilite d'un gene candidat et relation avec la maladie : applications aux genes de la cetp (proteine de transfert du cholesterol esterifie) et de l'apob (apolipoproteine b) dans la susceptibilite a l'infarctus du myocarde." Paris 11, 1998. http://www.theses.fr/1998PA11T001.
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Charpentier, Bruno. "Étude des promoteurs transcriptionnels des gènes gapA et gapB codant pour la glycéraldéhyde-3-phosphate déshydrogénase d'Escherichia coli. : relation structure/fonction." Nancy 1, 1994. http://www.theses.fr/1994NAN10307.
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L'expression des gènes gapA et gapB d'Escherichia coli, codant pour glycéraldéhyde-3-phosphate déshydrogénase, a été étudiée au niveau: organisation des régions promoteur et régulations transcriptionnelles. Des résultats inattendus ont été obtenus: la partie codante de gapA est précédée d'une région promoteur complexe permettant une forte expression, quelles que soient les conditions environnementales, 4 promoteurs ont été mis en évidence. Les promoteurs p1, p3 et p4 sont reconnus par l'ARN polymérase esigma70, alors que le promoteur p2 est reconnu par l'holoenzyme esigma32. Le promoteur p1 est responsable de la forte activité transcriptionnelle de gapA en phase exponentielle de croissance. L'efficacité de p1 dépend du degré de superenroulement de l'ADN et de la présence d'une courbure naturelle de l'ADN, localisée au niveau des boites -10 et -35. C'est la première observation du rôle d'une courbure à cette position dans un promoteur naturel. En condition de choc thermique ou de carence, l'utilisation de p2 est augmentée, tandis que celle de p1 décroit. D'ou l'extension du regulon de choc thermique aux gènes dont le niveau de transcription est simplement maintenu au cours du choc thermique. D'une manière surprenante, l'utilisation de p2 est forte pendant la phase exponentielle de croissance et cette forte utilisation dépend de la protéine fis. Le promoteur p3 est sous contrôle de la répression catabolique et son efficacité dépend également d'une courbure de l'ADN, centrée au niveau du site de fixation du complexe CRP/AMPC. Le gène gapB est transcrit et cette activité transcriptionnelle dépend de la présence de glucose, mais aussi de la protéine CRP et de l'AMPC. Cette régulation opposée à la régulation catabolique classique a aussi été observée pour l'operon PTS. Aucune protéine n'étant produite a partir du gène gapB, il est vraisemblable que l'activité transcriptionnelle observée permette l'expression des gènes adjacents à gapB: PGK et FDA
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Junit, Sarni Mat. "Regulation of human HMGCoA reductase and LDL receptor gene expression in relation to coronary heart disease and diet." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387665.
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Masih, Noreen. "An investigation of perirhinal activity-dependent gene transcription, CREB phosphorylation, and synaptic density in relation to recognition memory." Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.440042.
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Patel, Sameer. "Cardiopulmonary responses to acute hypoxia and exercise in relation to the angiotensin converting enzyme insertion/deletion gene polymorphism." Thesis, University of Glasgow, 2006. http://theses.gla.ac.uk/31016/.
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The physiological response to environmental hypoxia encountered at high altitude has a wide range of cardiovascular and pulmonary effects. The insertion allele of the angiotensin converting enzyme (ACE) gene polymorphism has been found to be more prevalent in endurance athletes and is associated with beneficial anabolic and functional responses in muscle. Furthermore, the insertion allele of this functional genetic polymorphism has been associated with enhanced physical performance at altitude, as defined by the successful ascent of peaks over 4800 metres. This thesis examines the cardiopulmonary responses during exercise and hypoxia in order to elucidate any genotype dependent differences in cardiopulmonary response that could explain this observation. The main body of this work was carried out between August 1999 and September 2001. The studies involved 60 healthy subjects performing a maximal cardiopulmonary exercise test to determine ventilatory threshold (VT). At the second visit the subjects underwent a second set of steady state exercise tests, performed at 50% of the work rate attained at VT, under normoxic and hypoxic conditions (FiO2 12.5%). Metabolic and ventilatory measurements were made during tests and the changes between normoxic and hypoxic response during rest and exercise were analysed. A second smaller study examined cardiac output response during hypoxia and exercise using bioimpedance cardiography. These studies were performed simultaneously with the cardiopulmonary exercise tests and included 31 subjects. Similar analyses were performed on cardiac output variables between normoxia and hypoxia. The repeatability of the steady state cardiopulmonary exercise experimental protocol was verified by repeat testing and analyses. Bioimpedance cardiography measurements were validated against simultaneous measurements during pulmonary catheter studies and thermodilution cardiac output measurement. The results of the tests and the comparison of response demonstrated a larger increase in ventilation during exercise from normoxia to hypoxia in the insertion homozygous group. This was accompanied by a genotype dependent decrease in end-tidal carbon dioxide, suggesting a higher alveolar ventilation. There was no increase in oxygen saturations in the insertion homozygous group, which may have been due to the technical limitations of the oximeters. The cardiac output studies did not reveal any significant difference between genotype. The ventilatory study has demonstrated a response that may contribute to enhanced performance during prolonged hypoxic exposure, as experienced at high altitude.
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Bienvenu, Thierry, and G. Buttin. "Heterogeneite des mutations et complexite de l'epissage du gene cftr : relation avec la variabilite clinique de la mucoviscidose." Paris 6, 1995. http://www.theses.fr/1995PA066260.
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La mucoviscidose est la maladie autosomique recessive la plus frequente dans la population caucasienne. Elle affecte approximativement un enfant sur 2500 naissances. Elle se caracterise par une grande variabilite clinique que ce soit dans son mode d'apparition ou dans la severite et la progression des manifestations cliniques. Le gene en cause dans cette affection a ete localise en 1985 sur le bras long du chromosome 7, puis clone et sequence 4 ans plus tard. Une deletion de 3 bases, denommee f508, est retrouvee sur environ 70% des chromosomes morbides. Depuis, environ 500 mutations ponctuelles ont ete identifiees le long de ce gene codant pour une proteine denommee cftr (cystic fibrosis transmembrane conductance regulator). Elles affectent toutes les regions critiques des 27 exons de ce gene de 230 kb. Au cours de ce travail, nous avons developpe de nouvelles methodes d'identification de mutations ponctuelles, telle l'electrophorese en gradient de gel denaturant (dgge) utilisant des amorces oligonucleotidiques modifiees par l'adjonction d'une molecule chimique, un psoralene. Ces methodes, associees a une strategie de detection des mutations du gene cftr, ont ete appliquees a l'identification des mutations du gene cftr dans une population de patients mucoviscidosiques d'origines ethniques variables vivant en region parisienne. Nous avons ainsi identifie sur la population etudiee plus de 92% des mutations (soit 53 mutations differentes) reparties sur 20 exons de ce gene. Ces resultats illustrent la difficulte de realiser dans notre region un programme efficace de depistage systematique. Au cours de ce travail, plusieurs nouvelles mutations ont pu etre identifiees. Certaines ont ete plus profondement analysees par l'etude des transcrits du gene (mutations affectant l'epissage) ou par l'etude des interactions adn-proteines (variations de sequence dans la region 5' promotrice du gene). L'ensemble de ces donnees genetiques nous a ensuite permis de tenter d'etablir des relations entre le phenotype clinique et le genotype, afin de mieux comprendre les raisons de l'heterogeneite clinique de cette affection. L'atteinte pancreatique semblerait ainsi dependre etroitement de la nature des mutations et la survenue de certaines complications pourrait etre associee a des mutations specifiques. L'atteinte respiratoire et notamment la precocite de la deterioration des parametres ventilatoires apparaissent aussi etre genetiquement determinees. Toutefois, l'existence d'une heterogeneite clinique au sein d'un groupe de patients ayant des mutations identiques suggere l'influence d'autres facteurs, genetiques et environnementaux. La complexite de l'epissage de l'arn pre-messager cftr, que nous avons notamment mis en evidence au niveau du pancreas humain sain adulte et foetal, pourrait etre l'une des explications a ces variations phenotypiques, notamment respiratoires. C'est dans ce but que nous avons analyse par rt-pcr la totalite de l'arnm cftr provenant de cellules de patients adultes notamment homozygotes f508 presentant des phenotypes cliniques differents. Il ressort de ce dernier aspect du travail que la perte de certains exons du transcrit cftr mute (exons 12, 16 et 17b) pourrait moduler l'expression clinique de l'affection, suggerant que la grande variabilite clinique de la mucoviscidose a bel et bien dans certains cas precis un support genetique lie au gene cftr. Ceci pourrait alors constituer un element pronostique non negligeable. Des etudes fonctionnelles sont en cours dans le but de verifier ces resultats
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So, King-yip Ken, and 蘇景業. "Gene organization of the lobster (Homarus americanus) Gonad inhibitinghormone, and its functional analysis in relation to vitellogenesis byRNA interference." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40203670.
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So, King-yip Ken. "Gene organization of the lobster (Homarus americanus) Gonad inhibiting hormone, and its functional analysis in relation to vitellogenesis by RNA interference." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/b40203670.
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Rozet, Jean-Michel. "Le gene abcr : HOMOGENEITE GENETIQUE VERSUS HETEROGENEITE CLINIQUE, UN PARADOXE AU SEIN DES DYSTROPHIES RETINIENNES HEREDITAIRES : UN MODELE DE CORRELATIONS génotype-phénotype." Paris 5, 2000. http://www.theses.fr/2000PA05N114.
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Axtner, Jan [Verfasser], and Simone [Akademischer Betreuer] Sommer. "Immune gene expression and diversity in relation to gastrointestinal parasite burden in small mammals / Jan Axtner. Betreuer: Simone Sommer." Potsdam : Universitätsbibliothek der Universität Potsdam, 2013. http://d-nb.info/1037027493/34.
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Stout, Jake. "Expression of a pectin methylesterase and a thaumtin gene in relation to deep supercooling in Vitis riparia Michx. buds." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/MQ58381.pdf.
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Rathjen, John Paul. "Aspects of luteovirus molecular biology in relation to the interaction between BYDV-PAV and the Yd2 resistance gene of barley /." Title page, contents and summary only, 1995. http://web4.library.adelaide.edu.au/theses/09PH/09phr2342.pdf.
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Xu, Ling. "Transcription Factor 7-like 2 (TCF7L2) Gene Polymorphisms in Relation to the Risk of Type 2 Diabetes in three ethnicities." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3815.
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Type 2 Diabetes (T2D) disproportionally affects ethnic minorities in the United States. The development of T2D involves complex interaction between environmental factors and genetic predisposition. The genetic associations of six single nucleotide polymorphisms (SNPs) in TCF7L2 gene with the risk of T2D were evaluated in three high risk minority populations: Cuban Americans, Haitian Americans, and African Americans. For Cuban Americans, four SNPs (rs7901695, rs4506565, rs7903146 and rs11225537) were significantly associated with the risk of T2D after multivariable adjustment (p=0.018, p=0.016, p=0.014, and p=0.0008, respectively). Among controls, risk allele carriers of SNPs rs7901695, rs4506565 and rs7903146 had significantly higher fasting glucose level, compared to non-risk allele carriers. Additionally, a significant interaction between dietary fiber intake and SNP rs7903146 for the risk of T2D (p= 0.044) was found in Cuban Americans. Similarly, for SNP rs7901695, significant interaction was also found for fiber intake (p=0.014) as well as glycemic load (p=0.040). Subgroup analysis revealed that significant associations were only found within higher intake groups of dietary factors for both SNPs. For Haitian Americans, SNPs rs11196205 (p=0.059) and rs7895340 (p=0.069) showed marginal significance for the risk of T2D. After stratification by gender, SNPs with marginal significance from the gender-combined analysis became statistically significant with the same trend for the risk of T2D when analysis were done in males: rs11196205 (p=0.034) and rs7895340 (p=0.024). For African Americans, SNP rs7903146 (p=0.065) showed a marginal significance with the risk of T2D in gender-combined analysis and a statistical significance (p=0.013) in males. Two additional SNPs rs7901695 and rs4506565 were found to be significantly associated with the risk of T2D in males. Risk allele carriers of these two SNPs had significantly higher mean level of the fasting glucose level, compared to non-risk allele carriers in controls. T2D related quantitative trait analysis also demonstrated that in controls, compared to non-minor allele carriers of SNP rs12255372, minor allele carriers had significantly higher means of BMI, diastolic blood pressure, numbers of components of Metabolic Syndrome, significantly lower mean values of HDL-cholesterol and adiponectin. Taken together, our studies demonstrated ethno-specific genetic associations between TCF7L2 gene and the risk of T2D and related phenotypes.
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McDonald, Zac Eliot. "Sucrose Phosphate Synthase activity and gene expression in relation to dehydration induced sucrose accumulation in the resurrection plan Xerophyta Humilis." Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/4295.
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Talerico, Cassandra. "Temporal Activation of the JAK-STAT Pathway in Relation to Cardiac Gene Expression in a Mouse Model of Cardiac Dysfunction." Cleveland State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=csu1197055735.
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Masli, Aryananda. "Search for restriction fragment length polymorphism of Phaseolus vulgaris in relation to the immune gene to bean common mosaic virus." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc798405/.
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A technique involving Restriction Fragment Length Polymorphism (RFLP) was used to observe the DNA fragment polymorphism between a bean cultivar with I/I genotype and a bean cultivar with i/i genotype. The I gene encodes immunity to bean common mosaic virus (BCMV).
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Hamza-Talha, Saliha. "Stimulation rapide du renouvellement de l'atp par des facteurs de croissance dans des fibroblastes de souris swiss : relation avec d'autres evenements precoces." Paris 6, 1987. http://www.theses.fr/1987PA066423.
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Depuis la mise en evidence de similitude entre des facteurs de croissance (fc) et des produits d'oncogenes, differents evenements biochimiques precocement induits par les fc sont decrits, cependant, leur chronologie n'est pas clairement determinee. Mise en evidence d'un nouvel evenement precoce: une stimulation du renouvellement de l'atp dans des cultures quiescentes de cellules 3t3 swiss incubees en presence de fc ou d'un promoteur de tumeur, utpa: activation de l'echange sodium-proton et de l'atpase sidium-potassium. Les mouvements cellulaires, induits precocement par les fc de par le tpa, sont impliques dans la degradation et le renouvellement rapides de l'atp. De plus, ils favorisent la stimulation par les fc de l'accumulation de certains arn messagers (actine et c-fos) et de la synthese d'arn ribosomiques
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Del, Prete Stefania. "Characterisation of transcriptional and chromatin events in relation to floral transition and identification of nuclear organisation determinants." Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS022.
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La transition florale résulte d’un jeu complexe d’interactions entre des signaux endogènes et environnementaux. Les feuilles jouent un rôle crucial dans ce processus en percevant les changements associés à la lumière et en produisant les photosynthétats qui participant à la signalisation de la floraison. Toutefois, notre connaissance des changements se produisant dans les feuilles lors de la transition florale reste limitée. Nous avons caractérisé les événements morphologiques, moléculaires et transcriptionnels en relation avec la floraison florale dans les feuilles matures chez Arabidopsis, en exploitant un système de transfert de conditions en jours courts vers des jours longs, transfert qui permet d’induire et synchroniser la floraison. Nous avons identifié la fenêtre temporelle de la transition florale, mesuré la croissance foliaire, et observé un accroissement de la ploïdie au cours du processus. Par une approche de RNA-seq, nous avons étudié la dynamique transcriptionnelle des réseaux de gènes dans la feuille, et comparé avec des données dans la racine et le méristème pour avoir une vue plus intégrée de la floraison dans la plante. De plus, nous avons analysé le mode d’action de LHP1 (LIKE HETEROPROTEIN 1), une sous unité du complexe PRC1, en exploitant des lignées transgéniques avec des modifications conditionnelles du dosage de LHP1 et en analysant les effets sur la chromatine et la transcription des gènes impliqués dans la floraison. Une modulation courte du dosage en LHP1 modifie le dépôt des marques H3K27me3 et H3K4me3, démontrant une interaction fonctionnelle entre LHP1 et le complexe PRC2, et suggérant aussi un nouveau rôle dans la formation de régions chromatiniennes de type bivalent. Enfin, étant donné le rôle clé de l’organisation nucléaire dans la régulation génique, nous avons recherché et identifié des déterminants de l’architecture nucléaire en utilisant de nouveaux outils de statistiques spatialesThe transition to flowering results from a complex interplay between endogenous and environmental cues. The leaves play a key role in this process, by perceiving the light changes and producing photosynthates, which participate to the floral signalling. However, our knowledge on the changes occurring in leaves during floral transition is still limited. We characterised the morphological, molecular and transcriptional events related to floral transition in mature leaves in Arabidopsis, using a short-day to long-day shift to induce a synchronized flowering. We identified the temporal window of the floral transition, monitored the leaf growth and observed an increase in their ploidy level during the process. By RNA-seq we studied the transcriptional dynamics of the leaf gene network, and compared with events occurring in roots and meristems to get an integrated view of floral transition in the whole plant. Furthermore, we investigated the mode of action of LIKE HETEROPROTEIN 1 (LHP1), a PRC1 subunit, by exploiting transgenic lines with conditional alterations of LHP1 dosage and analysing the effects on chromatin and transcription of flowering genes. A short-term modulation of LHP1 dosage altered the deposition of H3K27me3 and H3K4me3, showing a functional interaction between LHP1 and PRC2, and also suggesting a new role in the formation of bivalent chromatin regions. Finally, since nuclear organisation plays a key role in gene regulation, we searched and identified determinants of the nuclear architecture by using innovative spatial statistical tools
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Amandusson, Åsa. "Estrogen receptor expression in relation to pain modulation and transmission : experimental studies in rats /." Linköping : Department of Clinical and Experimental Medicine, Linköping University, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-17978.
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Grant, Kathleen Ann. "Analysis of the clinical utility of gene expression profiling in relation to conventional prognostic markers in South African patients with breast carcinoma." Thesis, Stellenbosch : Stellenbosch University, 2014. http://hdl.handle.net/10019.1/95824.
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Thesis (PhD)--Stellenbosch University, 2014.ENGLISH ABSTRACT: Breast cancer is a heterogeneous disease characterised by marked inter-individual variability in presentation, prognosis and clinical outcome. The recognition that morphological assessment has limited utility in stratifying patients into prognostic subgroups led to clinico-pathological classification of tumour biology, based on receptor expression using immunohistochemical (IHC) techniques. This standard is currently complemented by the development of gene expression profiling methodology that led to the identification of intrinsic molecular subtypes, reflecting tumour genetics as the true driver of biological activity in breast cancer. The study was based on the hypothesis that molecular classification of breast carcinomas integrated with established clinico-pathological risk factors will improve current diagnostic and risk management algorithms used in clinical decision-making. A pathology-supported genetic testing strategy was used to evaluate microarray-based gene profiling against diagnostic pathology techniques as the current standard. Clinico-pathological factors including age, number of positive axillary nodes, tumour size, grade, proliferation index and hormone receptor status was documented for 141 breast cancer patients (143 tumours) referred for microarray-based gene expression profiling between 2007 and 2014. Subsets of patients were selected from the database based on the inclusion criteria defined for three phases in which the study was performed, in order to determine 1) the percentage of patients stratified as having a low as opposed to high risk of distant recurrence using the 70-gene MammaPrint profile within the inclusion criteria, 2) correlation of HER2 status as determined by IHC and fluorescence in situ hybridisation (FISH) with microarray-based mRNA readout (TargetPrint), and 3) the relationship between hormone receptor determination as reported by standard IHC and molecular subtyping using the 80-gene BluePrint profile. Similar distribution patterns for MammaPrint low- and high-risk profiles were obtained irrespective of whether fresh tumour biopsies or formalin-fixed paraffin embedded (FFPE) tissue was used. During the first phase of the study, 60% of the 106 tumour specimens analysed with MammaPrint were classified as low-risk and 40% as high-risk using a newly-developed MammaPrint pre-screen algorithm (MPA) aimed at cost-saving. In the second phase of the study, performed in 102 breast tumours, discordant or equivocal HER2 results were found in four cases. Reflex testing confirmed the TargetPrint results in discordant cases, achieving 100% concordance regardless of whether fresh tumour or FFPE tissue was used for microarray analysis. For the third phase of the study 74 HER2-negative tumour samples were selected for comparative analysis. Statistically significant positive correlations were found between protein expression (IHC score) and mRNA (TargetPrint) levels for estrogen receptor (ER) (R=0.53, p<0.0001) as well as progesterone receptor (PR) (R=0.62, p<0.0001), while combined ER/PR tumour status was reported concordantly in 82.4% of these tumours. BluePrint was essential for interpretation of these results used in treatment decision-making. The MPA developed in South Africa in 2009 was validated in this study as an appropriate strategy to prevent chemotherapy overtreatment in patients with early-stage breast cancer. The use of microarray-based analysis proved to be a reliable ancillary method of assessing HER2 status in breast cancer patients. Risk reclassification based on the TargetPrint results helped to avoid unnecessary high treatment costs in false-positive cases, in addition to providing potentially life-saving treatment to those for whom it was indicated. While neither IHC nor TargetPrint estimation of intrinsic subtype correlated independently with the molecular subtype as indicated by BluePrint profiling, the ability to distinguish between basal-like and luminal tumours was enhanced when the combined protein and mRNA values was considered. Genomic profiling provided information over and above that obtained from routine clinico-pathological assessments. This finding supports the relevance of a pathology-supported genetic testing approach to breast cancer management, whereby advanced genomic testing is combined with existing clinico-pathological risk stratification methods for improved patient management.
AFRIKAANSE OPSOMMING: Borskanker is „n heterogene siekte wat gekenmerk word deur merkbare inter-individuele variasie in kliniese beeld, prognose en uitkoms. Die beperkings van morfologiese klassifikasie vir identifikasie van prognostiese subgroepe het gelei tot klinies-patologiese tumor karakterisering op grond van reseptor uitdrukking deur gebruik van immunohistochemiese (IHC) toetse. Hierdie standaard word tans gekomplementeer deur ontwikkeling van geenuitdrukking tegnologie wat gelei het tot die identifikasie van intrinsieke molekulêre subtipes, wat die tumor genetika reflekteer as die ware drywer van biologiese aktiwiteit in borskanker. Die huidige studie is gebaseer op die hipotese dat integrasie van die molekulêre klassifikasie van borskanker met konvensionele risiko klassifikasie skemas huidige diagnostiese en behandelings algoritmes kan verbeter vir kliniese besluitneming. „n Patologie-gesteunde strategie is gebruik om mikroplaat-gebaseerde geen profilering te evalueer teen standaard patologie diagnotiese tegnieke. Kliniese-patologiese faktore insluitend ouderdom, aantal positiewe aksillêre limfnodes, tumor grootte, gradering, proliferasie indeks en hormoon reseptor status is gedokumenteer in 141 borskanker pasiente (143 tumore) wat verwys is vir mikroplaat-gebaseerde geenuitdrukking profilering tussen 2007 en 2014. Pasiënt subgroepe is geselekteer uit die databasis volgens die insluitingskriteria soos gedefiniëer in die drie fases waarvolgens hierdie studie uitgevoer is, om vas te stel 1) watter proporsie pasiënte geklassifiseer word as lae- of hoë-risiko vir latere herhaling van die borskanker deur gebruik van die 70-geen MammaPrint profile binne die insluitingskriteria, 2) hoe korreleer HER2 status soos vasgestel deur IHC en fluoreserende in situ hybridisasie (FISH) toetsing met mikroplaat-gebaseerde RNA lesings (TargetPrint), en 3) wat die verwantskap is tussen hormoon reseptor status soos deur standaard IHC gerapporteer en molekulëre klassifikasie volgens die 80-geen BluePrint profiel. Soortgelyke verdelingspatrone vir MammaPrint lae- teenoor hoe-risiko profiele is waargeneem ongeag of vars tumor biopsies of formalien-gefikseerde paraffin bevattende weefsel gebruik is. Tydens die eerste fase van die studie is 60% van die 106 tumore as lae-risiko en 40% as hoë-risiko geklassifiseer met toepassing van die nuwe MammaPrint Presifting Algoritme (MPA) wat ontwikkel is met die doel op kostebesparing. In die tweede fase van die studie waar 102 tumore ingesluit is, het die resultate van vier gevalle verskil van mekaar of was onbepaald ten opsigte van HER2 status. Refleks herevaluering het die TargetPrint resultate bevestig in alle nie-ooreenstemmende gevalle, en 100% ooreenstemming is bereik ongeag of vars tumor biopsies of formalien-gefikseerde paraffin bevattende weefsel gebruik is vir mikroplaat analise. In die derde fase van die studie is 74 HER2-negative tumore selekteer vir vergelykende analise. Statisties beduidende positiewe korrelasies is waargeneem tussen proteïen uitdrukking (IHC) en mRNA (TargetPrint) vlakke vir die estrogeen reseptor (ER) (R=0.53, p<0.0001) sowel as progesteroon reseptor (PR) (R=0.62, p<0.0001), terwyl gekombineerde ER/PR reseptor status ooreenstemming getoon het in 82.4% tumore. BluePrint was noodsaaklik vir die korrekte interpretasie van die resultate wat gebruik is in kliniese besluitneming vir behandeling van pasiënte. The MPA wat in Suid Africa ontwikkel is in 2009, is gedurende hierdie studie bevestig as n toepaslike strategie om onnodige handeling met chemoterapie te voorkom in pasiënte met vroeë stadium borskanker. Die gebruik van mikroplaat-gebaseerde analise is aangetoon as „n betroubare aanvullende metode om HER2 status te evalueer. Risiko herklassifikasie gebaseer op TargetPrint resultate het onnodige hoë behandelingskoste in vals-positiewe gevalle vermy, sowel as om die verskaffing van potensieël lewensreddende behandeling vir die toepaslike pasiënte te verseker. Genomiese profilering het inligting addisioneel tot dit wat met roetine klinies-patologies metodes verkry kan word verskaf. Hierdie bevinding ondersteun die relevansie van „n patologie-gesteunde genetiese toets benadering tot hantering van borskanker, waardeur genomiese toetsing gekombineer word met bestaande klinies-patologiese risiko stratifisering metodes om pasiënt behandeling te verbeter.
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Hagen, Ørjan. "Muscle growth and flesh quality of farmed Atlantic halibut (Hippoglossus hippoglossus) in relation to season of harvest." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/642.
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Chen, Chin. "Nutrient regulation of the human ccaat/enhancer-binding protein beta and its relation to transcriptional control of the human asparagine synthetase gene." [Gainesville, Fla.] : University of Florida, 2004. http://wwwlib.umi.com/cr/ufl/fullcit?p3136933.
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Thesis (Ph.D.)--University of Florida, 2004.Typescript. Title from title page of source document. Document formatted into pages; contains 161 pages. Includes Vita. Includes bibliographical references.
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Rolhion, Christine. "Etude de l'expression de genes impliques dans l'agressivite et la chimioresistance des gliomes humains : relation avec les caracteristiques anatomo-cliniques des patients (doctorat : biologie cellulaire et moleculaire)." Clermont-Ferrand 1, 1999. http://www.theses.fr/1999CLF1MM06.
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