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Sokolova, Natalia Valerievna. "The role of vitamin A in embryonic lung development in mice." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320687.
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Hörnberg, Maria. "Effects of retinoic acid in the mouse olfactory sensory systems /." Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1371.
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Wang, Xiao Elston Timothy C. "Mathematical modeling of signaling pathway dynamics and stochastic gene expression." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,367.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Statistics and Operations Research." Discipline: Statistics and Operations Research; Department/School: Statistics and Operations Research.
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Wright, Alan. "Bayesian pathway analysis in epigenetics." Thesis, University of Plymouth, 2013. http://hdl.handle.net/10026.1/1286.
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A typical gene expression data set consists of measurements of a large number of gene expressions, on a relatively small number of subjects, classified according to two or more outcomes, for example cancer or non-cancer. The identification of associations between gene expressions and outcome is a huge multiple testing problem. Early approaches to this problem involved the application of thousands of univariate tests with corrections for multiplicity. Over the past decade, numerous studies have demonstrated that analyzing gene expression data structured into predefined gene sets can produce benefits in terms of statistical power and robustness when compared to alternative approaches. This thesis presents the results of research on gene set analysis. In particular, it examines the properties of some existing methods for the analysis of gene sets. It introduces novel Bayesian methods for gene set analysis. A distinguishing feature of these methods is that the model is specified conditionally on the expression data, whereas other methods of gene set analysis and IGA generally make inferences conditionally on the outcome. Computer simulation is used to compare three common established methods for gene set analysis. In this simulation study a new procedure for the simulation of gene expression data is introduced. The simulation studies are used to identify situations in which the established methods perform poorly. The Bayesian approaches developed in this thesis apply reversible jump Markov chain Monte Carlo (RJMCMC) techniques to model gene expression effects on phenotype. The reversible jump step in the modelling procedure allows for posterior probabilities for activeness of gene set to be produced. These mixture models reverse the generally accepted conditionality and model outcome given gene expression, which is a more intuitive assumption when modelling the pathway to phenotype. It is demonstrated that the two models proposed may be superior to the established methods studied. There is considerable scope for further development of this line of research, which is appealing in terms of the use of mixture model priors that reflect the belief that a relatively small number of genes, restricted to a small number of gene sets, are associated with the outcome.
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Georgiades, Pantelis. "Studies of the expression and function of the retinoid-X-receptor y gene in rodent embryonic development." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244677.
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Livingstone, Julie. "Gene expression and bioinformatics analysis of the isoflavonoid pathway in soybean." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=66992.
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The phenylpropanoid pathway is highly researched due to t he putative nutraceutical benefits of its secondary metabolites. The enzymes of this pathway are member of gene families, but the exact number of gene homologues has to date been unknown. In this study, expressed sequence tags (ESTs) were used to identify all homologues in the isoflavonoid pathway of soybean (Glycine max L. Merr.). Gene expression of all homologues in whole tissues, and at a cellular level in the pod was also investigated using laser capture microdissection (LCM) and real time reverse-transcription polymerase chain reaction (qRT-PCR). Computational promoter analysis was undertaken to identify common regulatory motifs among the gene homologues. We have identified novel 2-hydroxyisoflavanone dehydratase and isoflavone-7-O-glucosyltransferase homologues. Differential expression of multiple gene homologues was discovered in numerous tissues. Our promoter analysis discovered five motifs which were previously identified within the promoter regions of the phenylpropanoid pathway in other plant species.La plupart des gènes de la voie métabolique des phenylpropanoïdes chez le soya incluent plusieurs homologues, mais leur nombre exact pour chacun des gènes demeure inconnu. L'expression de tous les homologues fut observée dans plusieurs tissus et au niveau cellulaire dans la cosse utilisant les méthodes de « laser capture microdissection » et de « real-time reverse-transcription polymerase chain reaction ». Une analyse de promoteurs in silico a été réalisée afin d'identifier des motifs régulateur commun chez les homologues. Cette étude a identifié un gène 2-hydroxyisoflavanone dehydratase nouveau en plus de cinq gènes isoflavone-7-O-glucosyltransferase. En outre, l'expression différentielle de plusieurs des homologues fut observée surtout dans les racines, les cotylédons et dans la couche exocarpe de la cosse. L'analyse de promoteur a découvert cinq motifs, qui ont auparavant été identifiés aussi dans des promoteurs de la voie métabolique des phenylpropanoid de d'autres espèces de plantes.
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Stenico, Verena <1983>. "Genus Bifidobacterium: taxonomy studies and gene expression analysis on folate pathway." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6604/.
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Folates (vitamin B9) are essential water soluble vitamins, whose deficiency in humans may contribute to the onset of several diseases, such as anaemia, cancer, cardiovascular diseases, neurological problems as well as defects in embryonic development. Human and other mammals are unable to synthesize ex novo folate obtaining it from exogenous sources, via intestinal absorption. Recently the gut microbiota has been identified as an important source of folates and the selection and use of folate producing microorganisms represents an innovative strategy to increase human folate levels.
The aim of this thesis was to gain a fundamental understanding of folate metabolism in Bifidobacterium adolescentis. The work was subdivided in three main phases, also aimed to solve different problems encountered working with Bifidobacterium strains. First, a new identification method (based on PCR-RFLP of hsp60 gene) was specifically developed to identify Bifidobacterium strains. Secondly, Bifidobacterium adolescentis biodiversity was explored in order to recognize representing strains of this species to be screened for their folate production ability. Results showed that this species is characterized by a wide variability and support the idea that a possible new taxonomic re-organization would be required. Finally B. adolescentis folate metabolism was studied using a double approach. A quantitative analysis of folate content was complemented by the examination of expression levels of genes involved in folate related pathways. For the normalization process, required to increase the robustness of the qRT-PCR analysis, an appropriate set of reference genes was tested using two different algorithms. Results demonstrate that B.adolescentis strains may represent an endogenous source of natural folate and they could be used to fortify fermented dairy products. This bio-fortification strategy presents many advantages for the consumer, providing native folate forms more bio-available, and not implicated in the discussed controversy concerning the safety of high intake of synthetic folic acid.
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Stelios, Pavlidis. "Pathway based microarray analysis based on multi-membership gene regulation." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/6968.
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Recent developments in automation and novel experimental techniques have led to the accumulation of vast amounts of biological data and the emergence of numerous databases to store the wealth of information. Consequentially, bioinformatics have drawn considerable attention, accompanied by the development of a plethora of tools for the analysis of biological data. DNA microarrays constitute a prominent example of a high-throughput experimental technique that has required substantial contribution of bioinformatics tools. Following its popularity there is an on-going effort to integrate gene expression with other types of data in a common analytical approach. Pathway based microarray analysis seeks to facilitate microarray data in conjunction with biochemical pathway data and look for a coordinated change in the expression of genes constituting a pathway. However, it has been observed that genes in a pathway may show variable expression, with some appearing activated while others repressed. This thesis aims to add some contribution to pathway based microarray analysis and assist the interpretation of such observations, based on the fact that in all organisms a substantial number of genes take part in more than one biochemical pathway. It explores the hypothesis that the expression of such genes represents a net effect of their contribution to all their constituent pathways, applying statistical and data mining approaches. A heuristic search methodology is proposed to manipulate the pathway contribution of genes to follow underlying trends and interpret microarray results centred on pathway behaviour. The methodology is further refined to account for distinct genes encoding enzymes that catalyse the same reaction, and applied to modules, shorter chains of reactions forming sub-networks within pathways. Results based on various datasets are discussed, showing that the methodology is promising and may assist a biologist to decipher the biochemical state of an organism, in experiments where pathways exhibit variable expression.
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Newton, Sherylanne. "Noise-induced hearing loss : changes in gene expression in the auditory pathway." Thesis, University of Leicester, 2017. http://hdl.handle.net/2381/40895.
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Noise induced hearing loss is classically divided into permanent or temporary forms. Individuals with permanent threshold shifts (PTS) will permanently lose auditory sensitivity, whereas individuals with temporary threshold shifts (TTS) will experience elevated hearing thresholds immediately following noise exposure, which resolves over several weeks. TTS causes little lasting damage to the hair cell, stereocilia or supporting structures which form the organ of Corti within the inner ear, and was therefore considered “no harm, no foul”. However, recent evidence suggests that TTS and PTS also leads to, what has been termed, “silent damage”; neuropathic damage which causes the loss of synaptic innervation at the inner hair cell and a slowly developing neuronal death. This study investigates the gene expression changes which accompany this type of noise-induced damage in the spiral ganglion neuron (SGN). Previous studies of gene expression changes following noise insult have used whole cochlea preparations which do not differentiate between changes in different cochlear structures. Here we have used micro-dissection of the modiolus to focus on the SGNs and to minimise contribution from other cochlea structures. In order to maximise the amount of data collected from each experimental animal, cochlear nucleus (CN) samples were taken in parallel to look at noise-induced changes at this first region of the central auditory system. A 1.5hr noise exposure of 105 dB SPL broadband noise elicited a moderate form of PTS, characterized by an immediate threshold shift of up to 44 dB SPL, which partially recovers over 28 days. Tissue was collected at 1day, 7days and 28days following exposure and RNA-Sequencing was performed. Over the 28-day period 421 genes were significantly changed in the modiolus; these were suggestive of a chronic immune response and for the first time, fibrinogen and lipid dysregulation. In the cochlear nucleus, just 184 genes were altered over 28-days; changes to Trpv4, Trpm3 and TrkA may contribute to increases in cell excitability in the CN following noise exposure.
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Shen, Ying. "Regulation of EphA4 expression through the APC-mediated ubiquitin-proteasome pathway /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?BICH%202007%20SHEN.
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Chan, Ming Hang (Stanley), and stanley chan@baker edu au. "Investigation of The Intracellular Signalling Pathway for Interleukin-6 Gene Expression in Skeletal Muscle." RMIT University. Medical Sciences, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080206.091026.
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Figueira, Edwin C. Medical Sciences Faculty of Medicine UNSW. "???Stem Cell Pathway??? gene expression in human foetal limbus and cadaveric human limbal epithelium." Awarded by:University of New South Wales. School of Medical Sciences, 2006. http://handle.unsw.edu.au/1959.4/27455.
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Stem cells play a vital role in the turn over of permanently self-renewing tissues (e.g. corneal epithelium, epidermis, bone marrow). Stratified cornea epithelia serve, as ideal tissue models for studying ???stemness???, as the site of cells in the different stages of differentiation are anatomically easily identifiable. Studies targeting limbal stem cell maintenance, in-vitro gene expression during storage and differentiation will benefit future therapeutic applications (e.g. corneal transplantation). Knowledge of stem cell behaviour will help explain the pathophysiology of corneal related ocular surface disorders (e.g. idiopathic limbal stem cell deficiency, pterygium and limbal dermoids), establish new treatment modalities (e.g. allogenic cellular transplants) and help promote invivo expansion of residual stem cell populations in deficiency states. The major obstacle in the progress of research on limbal stem cells is the lack of knowledge of phenotypic markers of limbal epithelial stem cells. This project first studied the limbal expression of phenotypic markers that were discovered in other human adult and embryonic stem cell populations using microarray differential expression studies. Gene expression profiles of the relatively primitive human foetal limbus were compared with that of the central cornea. Microarray was also performed to identify the differential gene expression profile of cultured primary human limbal epithelial cells, when compared to the limbal epithelial cell population isolated after 5 serial cultures. 33 genes were upregulated in the human foetal limbus and primary cultured human limbal epithelium, when compared respectively to the central foetal cornea (first experiment) and the limbal epithelial cell population after the 5th trypsin passaged culture (second experiment). Four foetal limbal and primary limbal epithelial upregulated genes (CK15, CK14, Cdh3, and Wnt4) were confirmed to be upregulated by semi quantitative RT-PCR and immunohistochemical experiments on the human foetal cornea, adult human cadaveric cornea and cultured human limbal epithelial cells. The microarray defined phenotypic profile of both the foetal limbus and cultured adult limbal epithelial cells will help identify these cells in in-vitro and in-vivo states. The expression of these 4 selected markers in the limbal dermoid and pterygium suggests that limbal epithelial cells containing a stem cell population are involved in the pathogenesis of these two disorders.
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Negrete-Urtasun, Susana. "Aspects of the PH signal transduction pathway in the filamentous fungus Aspergillus nidulans." Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286883.
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Huang, Norman Jason. "Graph-based Support Vector Machines for Patient Response Prediction Using Pathway and Gene Expression Data." Thesis, Harvard University, 2013. http://dissertations.umi.com/gsas.harvard:11072.
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Over the past decade, multiple function genomic datasets studying chromosomal aberrations and their downstream implications on gene expression have accumulated across a variety of cancer types. With the majority being paired copy number/gene expression profiles originating from the same patient groups, this time frame has also induced a wealth of integrative attempts in hope that the concurrent analysis between both genomic structures will result in optimized downstream results. Borrowing the concept, this dissertation presents a novel contribution to the development of statistical methodology for integrating copy number and gene expression data for purposes of predicting treatment response in multiple myeloma patients.
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Brannon, Mark K. "Wnt pathway-mediated transcriptional regulation of the Xenopus dorsoanterior organizing gene siamois /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/9256.
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Masserdotti, Giacomo. "ZFP423 coordinates Notch Pathway, Bmp Signaling and EBF/COE transcription factors to regulate Hes5 Gene Expression." Thesis, Open University, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.527455.
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Qian, Shuiming. "Study of retrovirus and host interplay: RNA helicase A and microRNA pathway modulate viral gene expression." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1236621870.
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Guo, Hong. "Molecular therapy for peritoneal fibrosis targeting the TGF-b/Smad signaling pathway /." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B39557509.
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Guo, Hong, and 郭紅. "Molecular therapy for peritoneal fibrosis: targeting the TGF-{221}/Smad signaling pathway." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557509.
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Ikram, Mohammed S. "Analysis of Sonic Hedgehog signalling pathway gene expression in Basal Cell Carcinoma and in GLII induced systems." Thesis, Queen Mary, University of London, 2007. http://qmro.qmul.ac.uk/xmlui/handle/123456789/1527.
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Embryonic development is regulated by a number of signalling pathways, which are critical for normal growth. Many of these genes then continue to play an important role in the regulation of cell growth and differentiation in adult. One such pathway is the sonic hedgehog (SHH) pathway; SHH protein is secreted which binds to its receptor patched (PTCH), leading to the activation and repression of target genes via zinc-finger GLI family transcription factors. Deregulation of this pathway, leads to a number of human birth defects and diseases such as Basal Cell Carcinoma (BCC) of the skin. In transgenic mouse model systems activation of GLI1 by SHH-signalling is a key step in initiating BCC formation. However, there is limited understanding of the molecular mechanisms involved in response to hedgehog signalling and GLI activity in human BCC formation and how this pathway interacts with other pathways. The aim of this thesis was to establish in vitro and in vivo model systems to investigate the molecular events leading to BCC formation. I have shown that Gl.Il , Gi12, Gi13, PTCH, SMO and KlF4 were induced and a-TUB was repressed in BCC relative to normal skin. Using an in vitro model I further showed that Gl.ll , Gi12, Gi13, PTCH, SMO and a-TUB were induced and KlF4 was repressed in GLII expressing keratinocytes. Collaborative work with Dr Fritz Aberger's laboratory in Salzburg showed that Gl.Il and FOXEI are direct targets of GLI2 and I showed that Gl.I? and FOXEI were expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal skin as well as in BCC tumour islands suggesting a possible link between hair follicle and BCe. I further showed that epidermal growth factor (EGF) signalling reduces transcription activity of GLI1 by shuttling GLII out of nucleus and altering the expression of PTCH, SMO, Gil2 and Gl.B SHH genes. In addition, I demonstrated that whilst EGF induced Vimentin and Snail2 expression and GLII repressed their expression suggesting that GLI is able to counter epithelial-mesenchymal transition associated with EGF and this may in part explain why Bee very rarely metastasise. Furthermore, GLI1 appears to upregulate stem cell like signature and EGF downregulates this signature. Finally, we were able to generate a KRTI4- Floxed-GFP-Gill transgenic mouse but were unable to activate the target gene (KRTI4-GFP-GiIl). In conclusion, I have identified possible targets of GLI activity and shown interactions between EGF signalling and GLI that will help us to understand the potential molecular actions of SHH signalling with the goal of developing better therapeutic strategies.
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Ponnampalam, S. N. "A blood-based gene expression and signalling pathway analysis to differentiate between high and low grade gliomas." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1485644/.
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Introduction: Brain tumours are the 17th most common cancer worldwide. Gliomas are the most common of the primary brain tumours and are highly malignant. / Objectives: (a) To undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signalling pathways (b) To develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-glioma and control samples. / Methods: Blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4x44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP respectively. Microarray data were analyzed by Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired student T-test with a p-value < 0.01. Pathway enrichment was also performed with key genes within these pathways selected for validation with ddPCR. / Results: The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (FDR corrected value < 0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. / Conclusion: In this study, we have shown that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.
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Jabeen, Mehnaz. "Exploring the cAMP/PKA pathway in the corn smut pathogen Ustilago maydis through serial analysis of gene expression." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31354.
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Ustilago maydis is the causative agent of corn smut disease. The ability of the
fungus to switch from budding to filamentous growth is required for pathogenesis.
Mating type genes and signaling pathways (cAMP and MAPK) regulate morphogenesis
and pathogenesis in U. maydis. A novel protein Hgll appears to be a downstream
component of the cAMP pathway that influences cell morphology and sporulation during
infection. The focus of this work was to further explore the role of the hgll gene in U.
maydis through the construction of Serial Analysis of Gene Expression (SAGE) libraries
to compare the transcriptomes of wild type and hgll mutant strains. The SAGE approach
provides a quantitative gene expression profile and identifies differentially expressed
genes. A key result of the SAGE work was the identification of a number of
differentially expressed genes for putative zinc finger proteins in the transcriptome. A
hypothetical protein encoded by the cthl (Cystine 3-histidine) gene had similarity to a
zinc finger protein. This gene was disrupted to investigate its role in the morphology of
U. maydis and in disease progression. Phenotypic characterization of the cthl mutant
lead to the conclusion that the gene is required for normal morphology and completion of
the life cycle in U. maydis, and that it might also be involved in the regulation of cell
division. Overall, this work makes a contribution to our understanding of the cAMP
signaling pathway in U. maydis and provides a wealth of expression data for future
analysis.Land and Food Systems, Faculty of
Graduate
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Karuppanan, Senniappan S. "The role of MTOR pathway and growth factors as revealed by gene expression profiling in diffuse congenital hyperinsulinism." Thesis, University College London (University of London), 2014. http://discovery.ucl.ac.uk/1421065/.
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Congenital hyperinsulinism (CHI) is the commonest cause of recurrent and persistent hypoglycaemia in infants. Histologically there are two distinct types: focal and diffuse. The medical therapy for diffuse CHI involves diazoxide, glucagon and octreotide. The patients who are unresponsive to medical therapy require a near total pancreatectomy. However, this often fails to provide the best outcome as some patients continue to have recurrent hypoglycaemia whilst others develop diabetes mellitus in the long term. This study aimed to understand the gene expression pattern in the pancreatic tissues of the patients with diffuse CHI so as to identify novel mechanism(s) and therapeutic options. Gene expression microarray using RNA extracted from fresh frozen pancreatic tissue samples (obtained from children who underwent pancreatectomy) revealed significant overexpression of mammalian target of rapamycin (mTOR) and insulin-like growth factors in the diffuse CHI patients in comparison with normal controls. Immunostaining suggested an activation of mTOR pathway (which regulates cellular proliferation) in diffuse CHI and transdifferentiation of exocrine pancreatic elements into insulin producing cells, contributing to β-cell hyperplasia. Further clinical study on the role of the mTOR inhibitor sirolimus in patients with medically unresponsive diffuse CHI (who would have required pancreatectomy otherwise) revealed a good glycaemic response to sirolimus and the infants were able to come off intravenous fluids, glucagon and octreotide infusions, thereby preventing the need for a major surgery. Subsequent follow up to 12 months revealed that the patients were normoglycaemic on sirolimus therapy without any major side effects. Hence treatment with mTOR inhibitors offers an alternative therapeutic option for the patients with severe forms of diffuse CHI. Further studies involving larger group of patients to assess the long term safety and efficacy of mTOR inhibitors in the management of diffuse CHI are needed.
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Batarseh, Amani Musa. "Regulation of translocator protein 18-kDa (TSPO) gene expression through a protein kinase C (PKC) epsilon signal transduction pathway." Connect to Electronic Thesis (CONTENTdm), 2010. http://worldcat.org/oclc/642828809/viewonline.
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Ferdous, Amin J. "Cloning and Expression of a Tobacco Stearoyl-ACP Desaturase Gene SBIP24 and its Interaction with SABP2 in SA pathway." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2429.
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Salicylic acid binding protein 2 (SABP2) that converts methyl salicylate to salicylic acid (SA) plays an obligatory role in the SA-mediated disease resistance pathway in plants. SABP2 interacts with SBIP24 in a yeast two-hybrid screening. SBIP24 belongs to the stearoyl-acyl carrier protein-desaturase protein family. To biochemically characterize the SBIP24, it was cloned from tobacco leaves using RT-PCR and expressed in E. coli. Recombinant SBIP24 was affinity purified using Ni-NTA chromatography. RT-PCR was performed to determine the role of SABP2 in modulating the expression SBIP24. TMV infected transgenic C3 (control tobacco plant containing empty silencing vector) and 1-2 (SABP2-silenced) transgenic tobacco plants were used. Preliminary results indicate that SABP2 may regulate the expression of SBIP24 in tobacco plants. Further studies are needed to confirm these preliminary results.
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Griffitts, Amanda Aline. "Characterization of Host Plant Defense Responses to Parasitization by Orobanche aegyptiaca." Thesis, Virginia Tech, 2001. http://hdl.handle.net/10919/42763.
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Orobanche (spp.) are parasitic plants that attack the roots of many important crops. O. aegyptiaca penetrates the host root (aided by digestive enzymes) and forms connections to the host vascular tissue, from which it will withdraw all of its water and nutrient requirements. In order to control this weed, it is important to understand the relationship between the host and the parasite. To investigate how parasitism effects host defense pathways, we are studying the patterns of expression of host genes known to be involved in various aspects of plant defense responses. With respect to local defense responses, two genes of the isoprenoid pathway were studied, one of which is expressed in wounded tissue (hmg1), and another that is induced in response to wounding yet repressed in response to pathogen elicitors (squalene synthase). Genes analyzed that are associated with systemic defense include PR-1, PR-2, and PR-5, all of which are induced in response to pathogen attack as part of the systemic acquired resistance (SAR) response. Plant gene expression was studied using transgenic tomato plants containing hmg1-GUS fusions, and northern hybridization analysis of tobacco and Arabidopsis roots using gene-specific probes. Results indicated that expression of hmg1 is induced, PR-2 and squalene synthase are repressed, and PR-1a, PR-1, and PR-5 are not affected in tissue parasitized by O. aegyptiaca. Together, these results indicate a complex response to the parasite. Whereas hmg1 induction is consistent with O. aegyptiaca inflicting a simple wound-like injury, the repression of squalene synthase is consistent with plant recognition of a pathogen attack. In contrast, the failure of Orobanche to induce SAR- related PR-1 in tobacco and PR-1, PR-2, or PR-5 in Arabidopsis indicates an ability to avoid or perhaps inhibit some defense-related pathways. By comparing the regulation of these defense genes in response to O. aegyptiaca attack, we are able to gain a greater understanding of the host plant response to parasitization and explore potential gene candidates for future engineering strategies to create Orobanche resistant crops.Master of Science
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Budnjo, Almir. "Gene expression of MAP2K1 and Cyclin D1 in BDII rat model of Endometrial cancer." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-12869.
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Endometrial adenocarcinoma (EAC) is the most frequently diagnosed gynecological cancer of the female genital tract in the Western world. Research studies in EC is difficult to conduct on human tumor samples due to the complex nature of tumor arousal and genetic heterogeneousness in the human population. Therefore, inbred animal models can be promising tools to use in EC research due to similar histopathology and pathogenesis as humans. Studies performed on MAP2K1 and CCND1 has shown that their altered expression play a crucial role in carcinogenesis. CCND1 has been demonstrated to have oncogenic properties when overexpressed in human neoplasias. The aim of this study is to investigate gene expression levels of MAP2K1 and CCND1 in BDII rat model of endometrial adenocarcinoma cells. Quantitative real-time PCR was used to analyze expression levels of MAP2K1 and CCND1 genes in BDII/Han rat model of endometrial cancer cells using TaqMan approach. The differences in gene expression levels of MAP2K1 and CCND1 between pathologically EAC malignant and nonmalignant cells showed an upregulation of MAP2K1 and CCND1 in EAC malignant cells. The analyzed data presented observable mean differences between MAP2K1 and CCND1 in several endometrial cell lines that were examined. Although no statistical significance was reached, an alteration in gene expression levels in malignant and nonmalignant endometrial cells could be observed. Furthermore, this present study shows observable upregulation of MAP2K1 and CCND1 in endometrial carcinoma cells vs. nonmalignant endometrium cells and encourages further investigation of the role of CCND1 and MAP2K genes in endometrial carcinogenesis.
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Roberts, Kim G. "Exploration of the ErbB/Ras/MAPK signaling pathway in cancer by gene expression profiling with isoform-specific assay development and microarray technology." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 169 p, 2007. http://proquest.umi.com/pqdweb?did=1362532051&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Imbriolo, Jamie. "Increased flux through the hexosamine biosynthetic pathway leads to the induction of acetol-CoA caboxylase gene expression in the heart." Thesis, Stellenbosch : Stellenbosch University, 2008. http://hdl.handle.net/10019.1/21459.
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Thesis (MSc)--Stellenbosch University, 2008.ENGLISH ABSTRACT: Gene expression of the cardiac isoform of acetyl-CoA carboxylase (ACCb) is induced in a glucose-dependent manner. ACCb produces malonyl-CoA, a potent inhibitor of mitochondrial fatty acid uptake. Previous studies show that increased flux through the hexosamine biosynthetic pathway (HBP) under hyperglycaemic conditions may contribute to the development of insulin resistance. In light of this, we hypothesised that increased HBP flux induces cardiac ACCb gene expression thereby contributing to the onset of insulin resistance. We tested our hypothesis by transiently transfecting cardiac-derived rat H9c2 myoblasts with a 1,317 bp human ACCb promoter-luciferase construct (pPIIb-1317) and an expression construct encoding the rate-limiting step of the HBP i.e. glutamine: fructose 6-phosphate amidotransferase (GFAT). Overexpression of GFAT increased ACCb gene promoter activity by 75 ± 23% versus controls (n=6, p<0.001). When cotransfection experiments were repeated in the presence of varying concentrations of L-glutamine (0 mM, 4 mM, 8 mM), a substrate for the HBP, ACCb promoter activity was dose-dependently increased. To further corroborate these findings, we employed two inhibitors of GFAT, i.e. 40 μM azaserine and 40 μM 6-diazo-5-oxo-Lnorleucine were administered to transfected cells for a period of 24 hours. Here both azaserine and 6-diazo-5-oxonorleucine attenuated ACCb gene promoter activity. In agreement, co-transfections with two dominant negative GFAT constructs also diminished ACCb gene promoter activity. We next inhibited two enzymes of the HBP acting downstream of GFAT, i.e. O-GlcNAc transferase and O-GlcNAcase using alloxan (0.1 mM, 1 mM and 2 mM) and streptozotocin (5 mM and 10 mM), respectively, for a period of 24 hours. Addition of alloxan attenuated ACCb gene promoter activity by 35.6 ± 1.9% (n=16, p<0.001) and streptozotocin increased activity by 32 ± 12% (n=12, p<0.001). We also investigated USF1 and USF2 as transcriptional regulatory candidates for HBP-induced ACCβ promoter regulation. Our data implicates USF2 as an important transcriptional regulator of HBP-induced ACCβ promoter regulation. In summary, this study demonstrates that increased flux through the hexosamine biosynthetic pathway induces ACCb gene promoter activity. We further propose that such an induction would reduce cardiac fatty acid oxidation, thereby leading to intracellular lipid accumulation due to a mismatch between sarcolemmal FA uptake and mitochondrial FA oxidation in the insulin resistant setting (i.e. hyperlipidaemia).
AFRIKAANSE OPSOMMING: Geen uitdrukking van die kardiale isoform asetiel-KoA karboksilase (ACCb) word in ‘n glukose afhanklike wyse geïnduseer. ACCb produseer maloniel-KoA, ‘n kragtige inhibeerder van mitochondriale vetsuuropname. Vorige studies toon aan dat verhoogde fluks deur die heksosamien biosintestiese weg (HBW) onder hiperglukemiese toestande bydra tot die ontwikkeling van insulienweerstand. In die lig hiervan, word daar gehipotetiseer dat verhoogde HBP fluks kardiale ACCb geenuitdrukking induseer en so bydra tot die ontstaan van insulienweerstand. Ons hipotese is getoets deur die kardiale afkomstige rot H9c2 mioblaste met ‘n 1.317 bp mens ACCb-lusiferase promotor konstruk (pPII-1317) te transfekteer en ‘n uitdrukking te konstrueer wat die tempo bepalende stap van HBP i.e. glutamien: fruktose-6-fosfaat amidotransferase (GFAT) kodeer. Ooruitdrukking van GFAT verhoog ACCb geenpromotor aktiviteit deur 75 ± 23% teenoor kontrole (n=6, p<0.001). Die herhaling van ko-transfeksie eksperimente is herhaal in die teenwoordigheid van variëerbare L-glutamienkonsentrasies (0 mM, 4 mM, 8 mM), ’n substraat vir die HBP, ACCb promotor aktiwiteit is dosisafhanglik verhoog. Om die bevindinge verder te staaf, is twee inhibeerders van GFAT, i.e. 40 μM azaserien en 40 μM 6-diazo-5-oxo-L-norleusien aan transfeksie selle toegedien vir ’n tydperk van 24 uur. Beide azaserien en 6-diazo-5-oxo-L-norleusien verlaag ACCb geenpromotor aktiwiteit. In ooreenstemming met die bogenoemde het ko-transfeksies met twee dominante negatiewe GFAT konstrukte ook ACCb geenpromoter aktiwiteit verminder. Die volgende stap is om twee ensieme van die HBP wat stroomaf van GFAT aktief is, vir ‘n periode van 24 uur te inhibeer i.e. O-GlcNAc transferase en O-GlcNAcase deur alloxan (0.1 mM, 1 mM en 2 mM) and streptozotosien (5 mM en 10 mM) onderskeidelik vir ‘n 24 uur periode te gebruik. Toevoeging van alloxan het die ACCb geenpromotor aktiwiteit by 35.6 ± 1.9% (n=16, p<0.001) verlaag en streptozotosien aktiwiteit verhoog by 32 ± 12% (n=12, p<0.001). Ons het ook die USF1 en USF2 as transkripsie regulerings kandidate vir HBP-geïnduseerde ACCβ promotor regulering ondersoek. Ons data impliseer dat USF2 as ‘n belangrike transkripsie reguleerder van HBP-geïndiseerde ACCβ promotor regulering is. Samevattend het hierdie studie demonstreer dat verhoogde fluks deur die hexosamien biosintetiese weg ACCb geenpromotor aktiwiteit induseer. Ons stel verder voor dat hierdie induksie die kardiale vetsuuroksidasie verlaag wat daartoe lei dat intrasellulêre lipied akkumulasie as gevolg van onparing tussen sarkolemma vetsuuropname en mitochondriale vetsuuroksidasie in ’n insulien weerstandige situasie (i.e. hiperlipidaemia).
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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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Smith, David M. "A role for adenylyl cyclase and the CREB/CRE transctiptional pathway in mammalian behavior /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/6296.
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Weir, Kenneth. "A refinement to the semi-quantitative RT-PCR method and defense related, stress resistance and insulin pathway gene expression during Sarcophaga crassipalpis diapause." Diss., Online access via UMI:, 2008.
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Ting, Kin Lai. "A calcitonin gene-related peptide-induced signaling pathway directs the synaptic expression of collagen-tail subunit (ColQ) of acetylcholinesterase in muscle /." View abstract or full-text, 2005. http://library.ust.hk/cgi/db/thesis.pl?BIOL%202005%20TING.
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Angus, Liselotte. "Willin as a novel 4.1 ezrin radixin moesin (FERM) domain protein in the mammalian Hippo signalling pathway." Thesis, University of St Andrews, 2011. http://hdl.handle.net/10023/2489.
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The Salvador/Warts/Hippo (Hippo) pathway defines a novel signalling cascade regulating cell contact inhibition, organ size control, cell growth, proliferation, apoptosis and cancer development in mammals. The Hippo pathway was initially utilised in D. melanogaster, where the Expanded protein acts in the Hippo signalling cascade to control organ size. Willin is the proposed human orthologue of Expanded and the aim of this thesis is to investigate whether willin can activate the mammalian Hippo signalling pathway. Ectopic willin expression causes an increase in phosphorylation of the core Hippo signalling pathway components MST1/2, LATS1 and YAP, an effect which can be antagonised by ezrin. In MCF10A cells, willin over-expression antagonises a YAP-induced epithelial-to-mesenchymal transition via the N- terminal FERM (Four-point-one Ezrin Radixin Moesin) domain of willin. Preliminary results show that willin is expressed within the sciatic nerve of rat and mice, and within the neuromast cells in the zebrafish; suggesting that willin and the Hippo pathway may play a vital role in the developmental regulation within the peripheral nervous system. To conclude, willin influences Hippo signalling activity by activating the core Hippo pathway kinase cassette in mammalian cells.
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Burckin, Todd A. "Probing the integration of steps in the gene expression pathway through analysis of the SPT4-SPT5 transcription elongation complex in Saccharomyces cervisiae /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2004. http://uclibs.org/PID/11984.
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Pfister, Anna. "Outcomes of Myosin 1C Gene Expression Depletion on Cancer-related Pathways, in Vitro and in Clinical Samples." Licentiate thesis, Sahlgrenska Academy at University of Gothenburg, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-12981.
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The unconventional myosin IC has previously been suggested to be a haploinsufficient tumour suppressor. The mechanism for this action has hitherto been unknown, however, and hence we decided to attempt to elucidate the genes involved. The first study involved knock-down of MYO1C using siRNA technology followed by whole transcriptiome microarray analysis performed on samples taken at different time points post transfection. This revealed a cornucopia of differential expressions compared to the negative control, among them we found an early up-regulation of the PI3K/AKT pathway and the pathway for prostate cancer. Among the down regulated pathways we found endometrial-, colorectal cancer and small cell lung cancer as well as the cell cycle pathway which was a little counter intuitive to the hypothesis that MYO1C suppresses cancer. For the next study six different genes (CCND1, CCND2, CDKN2B, CDKN2C, MYC, RBL1) important for the transitions into S-phase of the cell cycle were therefore chosen for validation using qPCR. These six genes and MYO1C were analysed on both the original time series and a new biological replicate as well as a well stratified set of endometrial carcinoma samples. We were able to verify the significant down-regulation of CCND2 in both time series indicating that this is caused by the depletion of MYO1C. In the tumour samples we saw a negative correlation between the expression of MYO1C and FIGO grade corroborating results previously found by our group when looking at protein expression.
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Cheng, Lulu. "Statistical Methods for Genetic Pathway-Based Data Analysis." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/52039.
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The wide application of the genomic microarray technology triggers a tremendous need in the development of the high dimensional genetic data analysis. Many statistical methods for the microarray data analysis consider one gene at a time, but they may miss subtle changes at the single gene level. This limitation may be overcome by considering a set of genes simultaneously where the gene sets are derived from the prior biological knowledge and are called "pathways". We have made contributions on two specific research topics related to the high dimensional genetic pathway data. One is to propose a semi- parametric model for identifying pathways related to the zero inflated clinical outcomes; the other is to propose a multilevel Gaussian graphical model for exploring both pathway and gene level network structures.
For the first problem, we develop a semiparametric model via a Bayesian hierarchical framework. We model the pathway effect nonparametrically into a zero inflated Poisson hierarchical regression model with unknown link function. The nonparametric pathway effect is estimated via the kernel machine and the unknown link function is estimated by transforming a mixture of beta cumulative density functions. Our approach provides flexible semiparametric settings to describe the complicated association between gene microarray expressions and the clinical outcomes. The Metropolis-within-Gibbs sampling algorithm and Bayes factor are used to make the statistical inferences. Our simulation results support that the semiparametric approach is more accurate and flexible than the zero inflated Poisson regression with the canonical link function, this is especially true when the number of genes is large. The usefulness of our approaches is demonstrated through its applications to a canine gene expression data set (Enerson et al., 2006). Our approaches can also be applied to other settings where a large number of highly correlated predictors are present.
Unlike the first problem, the second one is to take into account that pathways are not independent of each other because of shared genes and interactions among pathways. Multi-pathway analysis has been a challenging problem because of the complex dependence structure among pathways. By considering the dependency among pathways as well as genes within each pathway, we propose a multi-level Gaussian graphical model (MGGM): one level is for pathway network and the second one is for gene network. We develop a multilevel L1 penalized likelihood approach to achieve the sparseness on both levels. We also provide an iterative weighted graphical LASSO algorithm (Guo et al., 2011) for MGGM. Some asymptotic properties of the estimator are also illustrated. Our simulation results support the advantages of our approach; our method estimates the network more accurate on the pathway level, and sparser on the gene level. We also demonstrate usefulness of our approach using the canine genes-pathways data set.Ph. D.
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Wang, Ying. "The role of the hypoxia-inducible factor pathway in bone development and repair." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/wang.pdf.
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Bailey, Kathryn Lafaye. "The Use of Microarrays in the Detection of the Gene Expression of Ribulose- 1,5- Bisphosphate Carboxylase/Oxygenase (RubisCO) in the Marine Environment." [Tampa, Fla.] : University of South Florida, 2007. http://purl.fcla.edu/usf/dc/et/SFE0002106.
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Rahman-Roblick, Rubaiyat. "The P53 pathway: role of telomerase and identification of novel targets : acts of a master regulator of tumor suppression /." Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-184-5/.
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Dean, Phillip T. "Characterization of a Putative Phospholipase D ´ Like Gene as a Lipid Signaling Modulator and Its Role in Salicylic Acid Mediated Defense Pathway in Nicotiana tabacum." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etd/2464.
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Plants are in a perpetual evolutionary arms race with a wide range of pathogens. Their sessile nature has led plants to evolve defense mechanisms that can quickly recognize a unique stressor and deploy a resistance tailored for a specific attack. The salicylic acid (SA) mediated defense pathway has been shown to be one of the major defense tactics plants can initiate to defend themselves against microbial pathogens. Following a pathogen attack high levels of methyl salicylate (MeSA) are produced that can be converted to SA by the enzyme salicylic acid binding protein 2 (SABP2). A yeast two-hybrid screening was performed to identify protein interactions with SABP2 to better understand the regulation of the enzyme on a cellular level. SBIP-436 is an interacting protein of tobacco SABP2 which showed high homology to phospholipase D-δ (PLD- δ). With an abundance of stimulators PLD- δ may be a lipid signaling modulator developed to perform various functions in different situations. PLD- δ may be a key player in a lipid signaling cascade in the SA mediated defense pathway. We present a novel Nicotiana tabacum PLD- δ putative gene construct. We demonstrate that the putative PLD- δ is subject to alternative splicing and its expression is differentially modulated under biotic and abiotic stress. Our results indicate that this putative PLD- δ may play a role in the SA mediated defense pathway.
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Clifton, Rachel. "The alternative oxidase gene family in arabidopsis : insights from a transcriptomic study." University of Western Australia. Biochemistry and Molecular Biology Discipline Group, 2006. http://theses.library.uwa.edu.au/adt-WU2006.0004.
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[Truncated abstract] Mitochondria play an essential role in diverse metabolic pathways in plants. Their primary roles are the oxidation of organic acids via the tricarboxylic acid cycle and the synthesis of ATP coupled to the transfer of electrons from reduced NAD+ to oxygen via the electron transport chain. Plant mitochondria also contain nonphosphorylating bypasses of the respiratory chain, catalysed by the alternative oxidase (AOX), type II NAD(P)H dehydrogenases (NDHs) and uncoupling proteins (UCPs). Each of these components bypasses energy conservation by either circumventing the formation or utilization of the electrochemical proton gradient, and each is encoded by a small gene family in Arabidopsis. It is proposed that the alterative pathways are likely to be involved in balancing cellular redox and energy status and in minimizing the production of ROS generated by over-reduction of basal respiratory chain components. Furthermore the alternative respiratory pathways are thought to play a role in plant responses to stress. In this study a transcriptomic approach was taken to investigate the role of the alternative respiratory pathways in Arabidopsis, with a focus on elucidating the role and regulation of the AOX gene family. Analysis of the expression of the five AOX genes in Arabidopsis over development and in a range of tissues revealed a unique spatiotemporal expression pattern for each gene. Expression profiling using quantitative RT-PCR, MPSS and microarrays detected an abundance of the AOX1a transcript throughout the plant and over development. The expression patterns of other AOX genes provide insight into their putative roles, AOX1b was expressed predominantly in the flower, AOX1d was particularly abundant in senescing leaves and AOX2 expression was only observed in the seed.
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Hennes, Thomas Verfasser], Jürgen [Akademischer Betreuer] Bernhagen, and Joost T. van [Akademischer Betreuer] [Dongen. "Gene expression analysis identifies theActivin/Inhibin signaling pathway as a target ofCSN5/JAB1 in colorectal epithelial cancer cells / Thomas Hennes ; Jürgen Bernhagen, Joost Thomas van Dongen." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1162451289/34.
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May, Patrick, Jan-Ole Christian, Stefan Kempa, and Dirk Walther. "ChlamyCyc : an integrative systems biology database and web-portal for Chlamydomonas reinhardtii." Universität Potsdam, 2009. http://opus.kobv.de/ubp/volltexte/2010/4494/.
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Background:
The unicellular green alga Chlamydomonas reinhardtii is an important eukaryotic
model organism for the study of photosynthesis and plant growth. In the era of modern highthroughput technologies there is an imperative need to integrate large-scale data sets from highthroughput experimental techniques using computational methods and database resources to provide comprehensive information about the molecular and cellular organization of a single organism.
Results:
In the framework of the German Systems Biology initiative GoFORSYS, a pathway
database and web-portal for Chlamydomonas (ChlamyCyc) was established, which currently features about 250 metabolic pathways with associated genes, enzymes, and compound information. ChlamyCyc was assembled using an integrative approach combining the recently published genome sequence, bioinformatics methods, and experimental data from metabolomics and proteomics experiments. We analyzed and integrated a combination of primary and secondary database resources, such as existing genome annotations from JGI, EST collections, orthology information, and MapMan classification.
Conclusion:
ChlamyCyc provides a curated and integrated systems biology repository that will
enable and assist in systematic studies of fundamental cellular processes in Chlamydomonas. The ChlamyCyc database and web-portal is freely available under http://chlamycyc.mpimp-golm.mpg.de.
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Krampis, Konstantinos. "Systems View Of The Soybean Genetic Mechanisms Involved In The Response To Plant Pathogen Infection." Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/37672.
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This thesis involves the important crop plant soybean (Glycine max), and provides a rich information resource for breeders and geneticists working towards improving traits for pathogen resistance.Results reported here provide a systemic view at both the genetic and biochemical level, and were generated by dataÂ-mining gene expression data from soybean cultivars inoculated with plant pathogens and also recombinant inbred line (RIL) populations.The genome variability based on Single Feature
Polymorphisms (SFPs) was measured for the first time in soybean, using a genetically diverse set of cultivated G. max lines and also a G. soja line. Additionally, a genetic map spanning all 20 soybean chromosomes groups were assembled in a large RIL population.The well studied metabolic
pathways from the model plant Arabidopsis thaliana, were reconstructed in G. max based on sequence similarity comparison between the genomes of the two species. We performed algorithmic analysis of pathways in our set of soybean lines and RILs using the gene expression data, and acquired a systemic view of the metabolic response to pathogen infection in different genetic backgrounds.Significant differences in the patterns of pathway perturbation was observed in the different lines, and also between four different chromosomal regions that have been known to contain genetic elements contributing to pathogen resistance.Ph. D.
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Momin, Amin Altaf. "Application of bioinformatics in studies of sphingolipid biosynthesis." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/34842.
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The studies in this dissertation demonstrate that the gene expression pathway maps are useful tools to notice alteration in different branches of sphingolipid biosynthesis pathway based on microarray and other transcriptomic analysis. To facilitate the integrative analysis of gene expression and sphingolipid amounts, updated pathway maps were prepared using an open access visualization tool, Pathvisio v1.1. The datasets were formatted using Perl scripts and visualized with the aid of color coded pathway diagrams. Comparative analysis of transcriptomics and sphingolipid alterations from experimental studies and published literature revealed 72.8 % correlation between mRNA and sphingolipid differences (p-value < 0.0001 by the Fisher's exact test).The high correlation between gene expression differences and sphingolipid alterations highlights the application of this tool to evaluate molecular changes associate with sphingolipid alterations as well as predict differences in specific metabolites that can be experimentally verified using sensitive approaches such as mass spectrometry. In addition, bioinformatics sequence analysis was used to identify transcripts for sphingolipid biosynthesis enzyme 3-ketosphinganine reductase, and homology modeling studies helped in the evaluation of a cell line defective in sphingolipid metabolism due to mutation in the enzyme serine palmitoyltransferase, the first enzyme of de novo biosynthesis pathway. Hence, the combination of different bioinformatics approaches, including protein and DNA sequence analysis, structure modeling and pathway diagrams can provide valuable inputs for biochemical and molecular studies of sphingolipid metabolism.
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Xu, Yaomin. "New Clustering and Feature Selection Procedures with Applications to Gene Microarray Data." Case Western Reserve University School of Graduate Studies / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=case1196144281.
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Al-Dhaheri, Mariam Hamad. "Molecular Mechanisms of Protein Kinase A Signaling Pathway on Estrogen Receptor Action in Breast Cancer." University of Toledo Health Science Campus / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=mco1174316210.
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Luo, Xuebin. "Structural Analysis of the Genes Encoding the Oxalocrotonate Branch of the Pseudomonas putida TOL Plasmid pDKI meta-cleavage Pathway and the Expression of the xy1G Gene Product in Escherichia coli." Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc500659/.
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Three overlapping DNA fragments from the lower operon of Pseudomonas putida TOL plasmid pDK1, covering the xy1IH genes and downstream flanking region, were cloned into pUC19. They include a 2.8 kbp XhoI fragment, a 2.7 kbp PstI fragment and a 2.0 kbp EcoRI-HindIII fragment. They were subjected to DNA sequence analysis. The xy1I (4-oxalocrotonate decarboxylase) and xy1H (4-oxalocrotonate tautomerase) genes were found to possess coding regions of 792 and 189 nucleotides, respectively. A possible transcriptional terminator resembling E. coli rho-independent terminators was identified downstream of the translational stop of xy1H. An additional stem and loop structure was found in the intergenic region between xy1I and xy1H. The individual ORF's of the oxalocrotonate branch (xy1G, xy1I and xy1H) have been cloned into pUC18/19. The expression of the xy1G gene in E. coli was successfully assayed spectrophotometrically.
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Legoedec, Jocelyne. "Le muscle squelettique humain : une source locale de complément. Analyse in vitro de la biosynthèse et de l'activation des protéines du complément par les myoblastes humains." Rouen, 1997. http://www.theses.fr/1997ROUES025.
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Ce mémoire de thèse présente l'étude de l'expression des protéines d'activation et de régulation du système du C par les myoblastes humains normaux et tumoraux en culture. Différentes approches expérimentales ont été utilisées pour l'analyse protéique dans les surnageants de culture (western-blot, marquage biosynthétique et immunoprécipitation, immunofluorescence, dosages ELISA) et pour l'analyse de l'expression des ARNm (RT-PCR). La régulation de cette synthèse par différentes cytokines est envisagée afin d'analyser les variations dans un contexte inflammatoire. Nous montrons que les myoblastes humains normaux sont capables in vitro d'exprimer l'ensemble des protéines des voies d'activation classique et alterne du C. De plus, ils peuvent activer directement le C autologue via la voie classique mais sont protégés de la lyse par l'expression abondante de protéines de régulation solubles et membranaires du système du C. D'une manière générale, les synthèses sont constitutives et stimulées par les cytokines de l'inflammation. Seul le CR1 n'est pas exprimé par les myoblastes et les myotubes, mais l'utilisation de CR1 soluble (CR1s) diminue l'activation du C par les myoblastes in vitro. Nous émettons l'hypothèse qu'une production endogène de C par le muscle squelettique in vivo pourrait avoir un rôle différent selon le niveau d'activation du système : une activation sublytique aurait un effet physiologique dans la régénération tissulaire tandis qu'une activation incontrôlée serait impliquée dans les processus pathologiques par amplification de l'inflammation et destruction cellulaire locale. Il sera important dans l'avenir de déterminer le rôle précis de l'expression locale de C dans le muscle squelettique. Actuellement, cette étude apporte des précisions qui peuvent être utiles pour améliorer l'utilisation de la cellule musculaire dans le cadre de la thérapie génique. L'utilisation in vitro et in vivo de CR1s dans de nombreuses pathologies expérimentales limite les dommages cellulaires inhérents au C. Le CR1s utilisé par voie systémique pourrait améliorer la thérapie génique en augmentant la survie des myoblastes injectés et donc l'efficacité de la production du facteur codé par le gène d'intérêt.