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1
Cai, Na. "Molecular markers of stress." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:95826e79-6ef0-4148-8478-5778994f97fc.
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Using data from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) Consortium study of major depressive disorder (MDD)on 11,670 Han Chinese women, this thesis describes an investigation on the etiology of MDD, a psychiatric disease that has eluded previous genetic studies as well as investigations of its mechanistic underpinnings. It asks: what happens during stress, how may it contribute to the risk of developing MDD, and why does it increase the risk of MDD in some people but not others. It presents three main findings. First, a GWAS on MDD conducted on 10,640 samples (5,303 cases and 5,337 controls) in the CONVERGE dataset found two genome wide significant associations with MDD, one lying at the 5' side of SIRT1, and the other in an intron of LHPP. Both signals have been replicated in a completely independent cohort of severe MDD cases and matched controls from Northern China, making them the first replicated association loci for MDD to date. Second, I found there are more copies of mtDNA in cases of MDD than controls and while the increase can be induced by stress, it is contingent on the depressed state. Further analyses of results from animal experiments showed stress increases mtDNA levels in a dose-dependent, reversible and tissue specific way that is mediated partly by stress steroids. Third, the total amount of heteroplasmy was found to increase with increasing mtDNA levels, and therefore is higher in cases of MDD than controls, consistent with a change in mitochondrial function observed in animal models of chronic stress. All three findings suggest stress causes changes in mtDNA, and this change may be larger in cases of MDD than controls. This difference between cases and controls may be due to differences in their regulation of mtDNA levels and sequence mutation during stress, and this may be genetically determined. This study provides a new perspective to the etiology of depression, suggesting it may have origins in metabolic regulation.
2
Pinto, Diana Maria de Figueiredo. "Molecular markers for diabetic nephropathy." Master's thesis, Universidade de Aveiro, 2015. http://hdl.handle.net/10773/15953.
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Mestrado em Bioquímica - Bioquímica ClínicaType 2 diabetes is one of the most common metabolic disorders in the world. Globally, the prevalence of this disorder is predicted to increase, along with the risk of developing diabetic related complications. One of those complications is diabetic nephropathy, defined by a progressive increase in proteinuria and a gradual decline in renal function. Approximately 25% to 30% of type 2 diabetic individuals develop this complication. However, its underlying genetic mechanisms remain unclear. Thus, the aim of this study is to contribute to the discovery of the genetic mechanisms involved in the development and progression of diabetic nephropathy, through the identification of relevant genetic variants in Portuguese type 2 diabetic individuals. The exomes of 36 Portuguese type 2 diabetic individuals were sequenced on the Ion ProtonTM Sequencer. From those individuals, 19 did not present diabetic nephropathy, being included in the control group, while the 17 individuals that presented the diabetic complication formed the case group. A statistical analysis was then performed to identify candidate common genetic variants, as well as genes accumulating rare variants that could be associated with diabetic nephropathy. From the search for common variants in the study population, the statistically significant (p-value ≤ 0.05) variants rs1051303 and rs1131620 in the LTBP4 gene, rs660339 in UCP2, rs2589156 in RPTOR, rs2304483 in the SLC12A3 gene and rs10169718 present in ARPC2, were considered as the most biologically relevant to the pathogenesis of diabetic nephropathy. The variants rs1051303 and rs1131620, as well as the variants rs660339 and rs2589156 were associated with protective effects in the development of the complication, while rs2304483 and rs10169718 were considered risk variants, being present in individuals with diagnosed diabetic nephropathy. In the rare variants approach, the genes with statistical significance (p-value ≤ 0.05) found, the STAB1 gene, accumulating 9 rare variants, and the CUX1 gene, accumulating 2 rare variants, were identified as the most relevant. Both genes were considered protective, with the accumulated rare variants mainly present in the group without the renal complication. The present study provides an initial analysis of the genetic evidence associated with the development and progression of diabetic nephropathy, and the results obtained may contribute to a deeper understanding of the genetic mechanisms associated with this diabetic complication.
A diabetes tipo 2 é um dos distúrbios metabólicos mais comuns no mundo. Globalmente, está previsto um aumento da sua prevalência, assim como um aumento do risco de desenvolver complicações associadas. Uma dessas complicações é a nefropatia diabética, definida pelo aumento progressivo de proteinúria e um declínio gradual da função renal. Aproximadamente 25% a 30% dos indivíduos com diabetes tipo 2 desenvolvem esta complicação. No entanto, os mecanismos genéticos associados permanecem por esclarecer. Posto isto, o objetivo deste estudo é contribuir para a identificação dos mecanismos envolvidos no desenvolvimento e progressão desta complicação, através da identificação de variantes genéticas relevantes, em indivíduos com diabetes tipo 2 na população portuguesa. Para isso, os exomas de 36 portugueses com diabetes tipo 2 foram sequenciados na plataforma Ion ProtonTM. Desses individuos, 19 não apresentavam nefropatia diabética, tendo sido incluídos no grupo de controlo, e os restantes 17 individuos, com a complicação diagnosticada, formaram o grupo dos casos. Uma análise estatística foi depois realizada para identificar, com base nas diferenças genéticas entre os dois grupos, variantes comuns, assim como genes que acumulam variantes raras candidatas, que podem explicar o risco acrescido ou diminuído para desenvolver a complicação. Na pesquisa das variantes comuns, as variantes rs1051303 e o rs1131620 no gene LTBP4, a variante rs660339 no UCP2, a variante rs2589156 no gene RPTOR, a variante rs2304483 no SLC12A3 e, por fim, a variante rs10169718 presente no gene ARPC2, foram, de todas aquelas consideradas estatisticamente significativas (p-value ≤ 0,05), as mais relevantes para a patogénese da nefropatia diabética. O rs1051303 e o rs1131620, assim como o rs660339 e o rs2589156, têm um efeito protetor, enquanto o rs2304483 e o rs10169718 foram considerados de risco, estando associados a indivíduos que sofrem da complicação referida. Pela abordagem utilizada para identificar as variantes raras, o gene STAB1, que acumula 9 variantes, e o gene CUX1, que acumula 2, foram, de todos os genes com significado estatístico (p-value ≤ 0,05), aqueles que se evidenciaram como sendo biologicamente relevantes. Ambos os genes foram considerados protetores, já que as suas variantes raras acumuladas estavam presentes maioritariamente nos indivíduos que não apresentam esta complicação renal. Este estudo providencia uma análise inicial das evidências genéticas associadas ao desenvolvimento e progressão da nefropatia diabética, podendo os seus reultados contribuir para uma melhor compreensão dos mecanismos genéticos que estão por detrás do seu surgimento.
3
Weigelt, Britta. "Molecular markers of breast cancer metastasis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2005. http://dare.uva.nl/document/88848.
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Bitalo, Daphne Nyachaki. "Implementation of molecular markers for triticale cultivar identification and marker-assisted selection." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71670.
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Thesis (MSc)--Stellenbosch University, 2012.Triticale is an amphidiploid that consists of wheat (A and B) and rye (R) genomes. This cereal is fast becoming important on a commercial basis and warrants further assessment for the better management and breeding of the hybrid. The assessment of the genetic diversity among the wheat and rye genomes within triticale can be obtained by using molecular markers developed in both donor genomes. Simple sequence repeats markers (SSRs) and amplified fragment length markers (AFLPs) have been previously used to assess the genetic diversity among triticale lines. SSRs are highly polymorphic markers that are abundant and which have been shown to be highly transferable between species in previous studies while AFLP markers are known to generate plenty of data as they cover so many loci. Thus, the aim of this study was to develop a marker system suitable to assess the genetic diversity and relationships of advanced breeding material (and cultivars) of the Stellenbosch University’s Plant Breeding Laboratory (SU-PBL). Therefore, both AFLP and SSR markers were initially analysed using eight triticale cultivars (with known pedigrees) to facilitate cultivar identification. Fourty-two AFLP primer combinations and 86 SSR markers were used to assess the genetic diversity among the Elite triticale cultivars. The AFLP primer combinations generated under average polymorphism information content (PIC) values. Furthermore, these markers generated neighbour-joining (NJ) and unweighted pair group method with arithmetic average (UPGMA) dendograms that displayed relationships that did not correspond with the available pedigree information. Therefore, this marker system was found not to be suitable. A set of 86 SSRs previously identified in both wheat and rye, was used to test the genetic diversity among the eight cultivars. The markers developed in wheat achieved 84% transferability while those developed in rye achieved 79.3% transferability. A subset of SSR markers was able to distinguish the cultivars, and correctly identify them by generating NJ and UPGMA dendograms that exhibited relationships that corroborated the available pedigree data. This panel of markers was therefore chosen as the most suitable for the assessment of the advanced breeding material. The panel of seven SSR markers was optimised for semi-automated analysis and was used to screen and detect the genetic diversity among 306 triticale entries in the F6, Senior and Elite phases of the SU-PBL triticale breeding programme. An average PIC value of 0.65 was detected and moderate genetic variation was observed. NJ and UPGMA dendograms generated showed no clear groupings. However, the panel of markers managed to accurately identify all cultivars within the breeding program. The marker panel developed in this study is being used to routinely distinguish among the advanced breeding material within the SU-PBL triticale breeding programme and as a tool in molecular-assisted backcross.
5
Valdman, Alexander. "Molecular genetic markers of prostate cancer development /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-618-9/.
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Larkin, Samantha. "Molecular characterisation of prostate cancer progression markers." Thesis, University of Portsmouth, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.511205.
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Steele, Katherine A. "Molecular markers in yellow rust of wheat." Thesis, University of Nottingham, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.243712.
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Hemmings, Karen Emily. "Cellular and molecular markers of oocyte quality." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445945.
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Laird, Alexander. "Molecular prognostic markers in renal cell carcinoma." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/17873.
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Renal cell carcinoma (RCC) is the most deadly of urological malignancies. While metastatic disease affects one third of patients at diagnosis, a further third of patients who undergo extirpative surgery with curative intent subsequently develop metastatic disease. Inconsistency in the clinical course ensures predicting subsequent metastasis is notoriously difficult, despite the routine use of prognostic clinico-pathological parameters in risk stratification. With greater understanding of pathways involved in disease pathogenesis, a number of biomarkers have been proposed to be of prognostic significance; however there are currently no molecular prognostic markers in clinical use. Genetic intra-tumoural heterogeneity (genetic ITH) has been described in clear cell RCC (ccRCC) and may limit the clinical translation of biomarkers. There has been no assessment of ITH at other molecular levels. The aim of this work was to define and compare proteomic, transcriptomic and DNA methylation ITH in ccRCC, and identify potential prognostic biomarkers. Using reverse phase protein arrays to study protein expression in multiple spatially separate regions of primary and metastatic ccRCC, proteomic ITH was demonstrated for the first time. Interestingly there was no significant difference in proteomic ITH in metastatic ccRCC tumour deposits compared to primary tumours. However, on analysis of differential protein expression between primary and metastatic ccRCC tissue using a tissue microarray and automated analysis of immunofluorescence, there was significantly greater expression of Ki67, p53, VEGFR1, SLUG and SNAIL in the metastases compared to the primary tumours. Subsequent profiling of gene expression and DNA methylation in multiple areas of the same primary tumours confirmed transcriptomic and methylomic ITH. On comparison of this multimolecular ITH, significantly greater proteomic ITH was seen compared to gene expression and DNA promoter methylation heterogeneity. Recent evidence suggests DNA methylation may be prognostically important in RCC and given the lower methylomic ITH in ccRCC, the identification of prognostic DNA methylation changes in ccRCC were pursued using the Infinium HumanMethylation450K Beadchip. Following development of an analysis pipeline, identification and validation of prognostic differentially methylated regions (DMR) was performed on an experimental cohort and published dataset respectively. Five DMRs, which were associated with disease recurrence in ccRCC, were identified. NEFM gene promoter methylation was the only DMR associated with cancer specific survival, independent of TNM stage and nuclear grade on multivariate analysis, which was confirmed on a third independent published dataset. This thesis therefore demonstrates multi-molecular ITH in ccRCC for the first time. Despite this, NEFM promoter methylation may be a useful independent prognostic marker of cancer specific survival.
10
Cooper, Grace. "Molecular Markers of Alzheimer’s and Parkinson’s Diseases." The Ohio State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=osu1523975395945636.
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Cao, Wenguang. "Wheat taxonomy and cultivar identification using molecular markers." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/nq24007.pdf.
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Stoltzfus, Patricia. "Molecular markers reflecting malignant transformation and tumor progression /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-888-2.
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Tascilar, Metin. "Clinical significance of molecular markers in pancreatic cancer." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/61858.
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Hopwood, N. D. "Molecular markers of mesoderm induction in Xenopus laevis." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317830.
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Kawesha, Anthony. "Prognostic molecular markers in resected ductal pancreatic carcinoma." Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7596/.
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Previous studies of molecular prognostic markers following resection for exocrine pancreatic cancer have produced conflicting results. The aim of this study was to undertake a comprehensive analysis of potentially useful markers in a large multicentre patient population and compare these markers with standard pathological prognostic variables. Formalin fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma were analysed from 157 patients (100 men and 57 women with a median [range] age of 60 [33-77] years) who had undergone pancreatectomy. Immunhistochemistry was used to detect expression of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclin D1, c-erbB-2 and c-erbB-3. In a selected number of p53 positive and negative staining cases, mutational analysis was undertaken using DNA obtained from microdissected specimens. Mutations in codons 12 and 13 of the K-ras oncogene were detected by SSCP and sequencing following DNA extraction and amplification by PCR. The median [range] survival post-resection was 12.5 [3-83] months. Abnormalities of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclin D1, c-erbB-2 and c-erbB-3 expression were found in 87%, 41%, 75%, 72%, 33% and 57% of cases, respectively. There was no significant correlation between expression of any of these markers and patient survival. K-ras mutations were found in 73 (75%) out of 97% cases with amplifiable DNA. The presence of K-ras mutation alone did not correlate with survival, but there were significant differences in survival according to the type of K-ras mutation (p=0.0007). Reduced survival was found in patients with GaT, cGT and GcT K-ras mutations compared to GtT, aGT and GaC mutations. In conclusion survival was associated with the type of K-ras mutation but not the expression of p16\(^{INK4}\), p53, p21\(^{WAF1}\), cyclinD1, c-erbB-2 and c-erbB3.
16
Hu, Jiahuai. "Phytophthora nicotianae: Fungicide Sensitivity, Fitness, and Molecular Markers." Diss., Virginia Tech, 2007. http://hdl.handle.net/10919/26416.
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Mefenoxam has been a premier compound for Phytophthora disease control in the nursery industry for 30 years. The primary objectives of this research were to examine whether Phytophthora species have developed resistance to this compound and to investigate fungicide resistance management strategies. Phytophthora nicotianae, a destructive pathogen of numerous herbaceous and some woody ornamental plants, was used as a model system. P. cinnamomi, a major pathogen of a wide range of tree species and shrub plants, was also included for comparison.
Twenty-six isolates of P. nicotianae were highly resistant to mefenoxam with a mean EC50 value of 326.5 µg/ml while the remaining 70 were sensitive with an EC50 of <0.01 µg/ml (Label rate: 0.08µg/ml). All resistant isolates were recovered from herbaceous annuals and irrigation water in 3 Virginia nurseries. Resistant isolates were compared with sensitive ones using seedlings of Lupinus â Russell Hybridsâ in the absence of mefenoxam for relative competitive ability. Resistant isolates out-competed sensitive ones within 3 to 6 sporulation cycles. Resistant isolates exhibited greater infection rate and higher sporulation ability than sensitive ones.
No mefenoxam resistant isolates were identified in P. cinnamomi. All 65 isolates of P. cinnamomi were sensitive to mefenoxam with an EC50 of < 0.04 ï g/ml. Attempts to generate mutants with high resistance to mefenoxam through UV mutagenesis and mycelial adaptation were not successful. However, there were significant reductions in sensitivity to mefenoxam; those slightly resistant mutants carried fitness penalties, which may explain why P. cinnamomi remains sensitive to mefenoxam.
The effect of propamocarb hydrochloride on different growth stages of Phytophthora nicotianae was evaluated in search for an alternative fungicide. Propamocarb greatly inhibited sporangium production, zoospore motility, germination and infection. However, it has little inhibition of mycelial growth and infections. Propamocarb can be used as an alternative fungicide to mefenoxam where mefenoxam resistance has become problematic. However, it must be used preventively; i.e. before infections occur.
The genetic inheritance of mefenoxam resistance in P. nicotianae was studied using F1 progenies of a cross between resistant and sensitive isolates. The F1 progenies segregated for mefenoxam resistance in ratio of 1R:1S, indicating the mefenoxam resistance is controlled by a single dominant gene. One RAPD marker putatively linked to resistant locus in repulsion phase was obtained by bulked segregant analysis and was converted to the SCAR marker. This marker is capable of differentiating mefenoxam resistant populations from sensitive populations included in this study.Ph. D.
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Sarela, Abeezar Ismail. "Molecular genetic markers of prognosis in colorectal carcinoma." Thesis, University of Leeds, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.438485.
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au, Constantine@wehi edu, and Clare Constantine. "Molecular markers, analysis and the population genetics of parasites." Murdoch University, 2002. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20050817.102006.
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In this study different molecular techniques are contrasted (RAPD's, allozyme, sequencing mtDNA, sequencing ribosomal spacers) and appropriate analytical methods (allelic and infinite-sites approaches; inbreeding and coalescent models) used for estimating population genetic parameters in parasites. A range of population genetic questions at different scales were chosen to emphasise the importance of tailoring techniques and analytical methods to the particular question being investigated.
The realisation that each question formulated has a particular scale means the appropriate technique and markers must be useful at that scale to attempt to answer the question. The useful scale of a technique depends several factors including the region of DNA examined, the density of sampling of the technique, and the mode of evolution of the markers. Each technique will produce a useful range of variability. Below the lower limit there is no variation, above the upper limit the variation is too high to produce useful comparisons.
Parasites are of interest for many reasons, primarily because they can cause disease and thus impact on their host's population dynamics. They are often closely associated with their hosts and may undergo co-evolution, as well as causing an ongoing immunological "arms race" with their hosts. The parasitic mode of live is found throughout nearly all taxonomic groupings and thus classical models of population genetics based on sexual, diploid vertebrates do not fit well with the entire diversity of parasite groups.
Genetic diversity within and among populations of Echinococcus granulosus was examined contrasting a RAPD dataset with an allozyme dataset. Two models of variation in Echinococcus have been proposed, those of Smyth and Rausch, and the expected genetic structure from each was compared to the observed genetic structure. The premise of Smyths model, predominant self-fertilisation, was supported, but the resultant pattern of genetic variation followed Rauschs model.
RAPD data, being dominant, present challenges to analysis. An approach to overcome this dominance problem and allow standard allelic frequency analysis is described using the selfing rate estimated from allozyme data. The RAPD data were also analysed using both band-sharing and nucleotide diversity approaches.
A population genetic study of Ostertagia ostertagi in the USA was extended to two different scales: within an Australian state and between the USA and Australian continents. Three alternative explanations for the observed discrepancy between genetic structure and differentiation in an important biological trait, hypobiosis, were explored. A number of programs and analyses were compared including coalescent geneflow estimates.
Variation among multiple copies of two spacer regions of rDNA was examined within individuals of Ostertagia ostertagi. Both the intergenic spacer and internal transcribed spacer 1 regions were found to include repeat regions, with different numbers of repeats creating length differences in clones from the same worm. Multi-copy genes present extra challenges in analysis to ensure that only homologous copies are being compared. Many studies fail to look for variation within populations or within individuals.
The two major conclusions from these examples are that:
1). The study of variation necessarily involves an implicit scale, and markers must be chosen that are appropriate to the question being explored.
2). Using several methods of analysis of genetic data allows contrasts to be made, and if different methods produce similar results gives much more confidence in the conclusions drawn. Incongruence in results leads to new questions and reexamination of the assumptions of each analysis.
19
Constantine, Clare. "Molecular markers, analysis and the population genetics of parasites." Constantine, Clare (2002) Molecular markers, analysis and the population genetics of parasites. PhD thesis, Murdoch University, 2002. http://researchrepository.murdoch.edu.au/662/.
Full textAbstract:
In this study different molecular techniques are contrasted (RAPD's, allozyme, sequencing mtDNA, sequencing ribosomal spacers) and appropriate analytical methods (allelic and infinite-sites approaches; inbreeding and coalescent models) used for estimating population genetic parameters in parasites. A range of population genetic questions at different scales were chosen to emphasise the importance of tailoring techniques and analytical methods to the particular question being investigated.
The realisation that each question formulated has a particular scale means the appropriate technique and markers must be useful at that scale to attempt to answer the question. The useful scale of a technique depends several factors including the region of DNA examined, the density of sampling of the technique, and the mode of evolution of the markers. Each technique will produce a useful range of variability. Below the lower limit there is no variation, above the upper limit the variation is too high to produce useful comparisons.
Parasites are of interest for many reasons, primarily because they can cause disease and thus impact on their host's population dynamics. They are often closely associated with their hosts and may undergo co-evolution, as well as causing an ongoing immunological "arms race" with their hosts. The parasitic mode of live is found throughout nearly all taxonomic groupings and thus classical models of population genetics based on sexual, diploid vertebrates do not fit well with the entire diversity of parasite groups.
Genetic diversity within and among populations of Echinococcus granulosus was examined contrasting a RAPD dataset with an allozyme dataset. Two models of variation in Echinococcus have been proposed, those of Smyth and Rausch, and the expected genetic structure from each was compared to the observed genetic structure. The premise of Smyth's model, predominant self-fertilisation, was supported, but the resultant pattern of genetic variation followed Rausch's model.
RAPD data, being dominant, present challenges to analysis. An approach to overcome this dominance problem and allow standard allelic frequency analysis is described using the selfing rate estimated from allozyme data. The RAPD data were also analysed using both band-sharing and nucleotide diversity approaches.
A population genetic study of Ostertagia ostertagi in the USA was extended to two different scales: within an Australian state and between the USA and Australian continents. Three alternative explanations for the observed discrepancy between genetic structure and differentiation in an important biological trait, hypobiosis, were explored. A number of programs and analyses were compared including coalescent geneflow estimates.
Variation among multiple copies of two spacer regions of rDNA was examined within individuals of Ostertagia ostertagi. Both the intergenic spacer and internal transcribed spacer 1 regions were found to include repeat regions, with different numbers of repeats creating length differences in clones from the same worm. Multi-copy genes present extra challenges in analysis to ensure that only homologous copies are being compared. Many studies fail to look for variation within populations or within individuals.
The two major conclusions from these examples are that:
1). The study of variation necessarily involves an implicit scale, and markers must be chosen that are appropriate to the question being explored.
2). Using several methods of analysis of genetic data allows contrasts to be made, and if different methods produce similar results gives much more confidence in the conclusions drawn. Incongruence in results leads to new questions and reexamination of the assumptions of each analysis.
20
Constantine, Clare Colleen. "Molecular markers, analysis and the population genetics of parasites /." Access via Murdoch University Digital Theses Project, 2002. http://wwwlib.murdoch.edu.au/adt/browse/view/adt-MU20050817.102006.
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Hoerder, Anna. "Mouse cortical subplate neurones : molecular markers, connectivity and development." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442449.
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Conway, Caroline Anne. "Identification of molecular markers of prognosis in malignantm melanoma." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496124.
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Cheung, Nga-yin Annie, and 張雅賢. "Cervical cancer screening: evolution from Paptest to molecular markers." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46540465.
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Ambrosini, Spaltro Andrea <1978>. "Immunohistochemical and Molecular Prognostic/Predictive Markers in Neoplastic Diseases." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2012. http://amsdottorato.unibo.it/4309/.
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Traditional morphological examinations are not anymore sufficient for a complete evaluation of tumoral tissue and the use of neoplastic markers is of utmost importance. Neoplastic markers can be classified in: diagnostic, prognostic and predictive markers. Three markers were analyzed.
1) Insulin-like growth factor binding protein 2 (IGFBP2) was immunohistochemically examined in prostatic tissues: 40 radical prostatectomies from hormonally untreated patients with their preoperative biopsies, 10 radical prostatectomies from patients under complete androgen ablation before surgery and 10 simple prostatectomies from patients with bladder outlet obstruction. Results were compared with α-methylacyl-CoA racemase (AMACR). IGFBP2 was expressed in the cytoplasm of untreated adenocarcinomas and, to a lesser extent, in HG-PIN; the expression was markedly lower in patients after complete androgen ablation. AMACR was similarly expressed in both adenocarcinoma and HG-PIN, the level being similar in both lesions; the expression was slightly lower in patients after complete androgen ablation.
IGFBP2 may be used a diagnostic marker of prostatic adenocarcinomas.
2) Heparan surface proteoglycan immunohistochemical expression was examined in 150 oral squamous cell carcinomas. Follow up information was available in 93 patients (range: 6-34 months, mean: 19±7). After surgery, chemotherapy was performed in 8 patients and radiotherapy in 61 patients. Multivariate and univariate overall survival analyses showed that high expression of syndecan-1 (SYN-1) was associated with a poor prognosis. In patients treated with radiotherapy, such association was higher.
SYN-1 is a prognostic marker in oral squamous cell carcinomas; it may also represent a predictive factor for responsiveness to radiotherapy.
3) EGFR was studied in 33 pulmonary adenocarcinomas with traditional DNA sequencing methods and with two mutation-specific antibodies. Overall, the two antibodies had 61.1% sensitivity and 100% specificity in detecting EGFR mutations.
EGFR mutation-specific antibodies may represent a predictive marker to identify patients candidate to tyrosine kinase inhibitors therapy.
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Chapman, Natalie HeÌleÌ€ne. "Identification and mapping of molecular markers for eyespot resistance." Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426603.
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Leal, Soraya Cristina de Macedo. "Detection and characterization of Metarhizium anisopliae using molecular markers." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307762.
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Hall, Nicola. "Stable isotopes, molecular markers and water use in Brassicas." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324874.
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Allender, Charlotte Jane. "Molecular markers and the speciation of African cichlid fish." Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394101.
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Schrag, Tobias A. "Prediction of hybrid performance in maize using molecular markers." [S.l. : s.n.], 2008. http://nbn-resolving.de/urn:nbn:de:bsz:100-opus-3035.
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Burrows, Kimberley. "Molecular genetic epidemiology studies of quantitative nucleic acid markers." Thesis, University of Bristol, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.761240.
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Plata-Muñoz, Juan José. "Clinical, biochemical and molecular markers of injury before transplantation." Thesis, University of Oxford, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.572681.
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The use of organs from donors after circulatory death (DCD) has been recommended as one strategy to enlarge the donor pool and raise the transplant rate. However, DCD allografts had higher incidence of early post-transplant dysfunction. The general aim of this research project was to develop clinical and experimental strategies to reduce the incidence of early post-transplant dysfunction of kidney and liver allografts from DCD. First the ability of a clinical scoring system based on donor data for identifying DCD kidneys with high-risk of post-transplant dysfunction was evaluated using the Oxford and the UK National DCD kidney transplant cohorts. This works suggest that stratification of DCD kidneys before transplantation might allow early identification of kidneys in which lower graft function and survival could be expected if any additional therapeutic intervention is implemented. Second, as it has been suggested that hypothermic machine perfusion (HMP) may protect DCD kidneys from additional preservation injury and improve their outcome after transplantation, this work explored the benefit of HMP as preservation technique fo DCD kidneys in Oxford and discusses the potential of this technique for reducing the incidence of post-transplant dysfunction in DCD kidneys. The Oxford. Liver Group has provided evidence of the benefit of preservation with normothermic machine perfusion (NMP) on post-transplant function and survival of DCD liver allografts. In this work, the molecular mechanisms associated with this benefit were characterized using micro array technology. This analysis suggests that the beneficial effect ofNMP may be associated with the induction of the ischaemic preconditioning phenomenon and highlights a group of genes with potential for gene therapy. Finally, this works provides the "proof-of-concept" that the use of a non-mammalian viral vector for gene transfer of kidneys and livers during conventional cold preservation is feasible and is not associated with additional tissue injury.
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Poli, Maurizio. "Novel molecular markers for assessment of human embryo competence." Thesis, University of Oxford, 2016. http://ora.ox.ac.uk/objects/uuid:4c5bffff-d12c-4df1-b5f0-1459298fc45c.
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In vitro fertilization treatments are responsible for 1-5% births in industrialized countries. The safest way to generate a pregnancy is to transfer a single embryo to the mother, reducing the likelihood of multiple gestations. Hence, in order to maximize the chance of success, it is extremely important that the embryo prioritised for transfer is the most capable within the cohort of embryos generated by the patient. Along with cytogenetic components, it has been suggested that embryo protein expression patterns may correlate with its ability to implant. However, embryo proteomics strategies have not been easy to harness mainly due to the complexity of the media the embryos are cultured in, and the low concentration of the proteins that are secreted. In this study, the use of the blastocentesis procedure, which allows the safe retrieval of embryo inner fluid (blastosol), was described. The use of the blasocoel fluid as a source of embryonic DNA for preimplantation genetic assessment was also investigated. From this highly purified embryonic sample, a comprehensive catalogue of proteins present in the human blastosol was generated using standard and custom- made mass spectrometry strategies. The embryonic origin of these proteins was validated by gene expression microarray and RNASeq analysis. These experiments also allowed the identification of differentially expressed genes in the first two cell lineages, the Inner Cell Mass and the Trophectoderm. Finally, a targeted proteomics strategy able to measure part of the previously described protein targets in single blastosol samples was employed. The correlation between the presence and abundance of proteins of interest in single blastosols and several biological characteristics of the embryo, including its chromosomal status, was assessed. These data are of major interest for the understanding of human embryo development. The validated embryo-derived protein catalogue and blastocyst gene expression profiles generated in this study, provides access to a thorough document for consultation in human embryology proteomics-based experiment design, paving the way to next-generation proteomic-based embryo assessment.
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Ishiy, Felipe Augusto André. "Evaluation of molecular markers in osteogenic differentiation of mesenchymal stem cells." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/41/41131/tde-20032017-104921/.
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The use of stem cells is a promising therapeutic approach for tissue engineering by their ability to boost tissue regeneration, and to model in vitro human genetics disorders since it provides continuous supplies of cells with differentiation potential. Our study has been focused in the identification of molecules or mechanisms that could contribute to a better osteogenesis in mesenchymal stem cells (MSC). To achieve our goals we have explored the osteopontential differences of stem cells from different sources. In this regard, we have observed that MSCs from human exfoliated deciduous teeth (SHED) presented higher in vitro osteogenic differentiation potential (OD) as compared to MSCs derived from human adipose tissue (hASCs). Through microarray analysis and cell sorting, we have shown that IGF2 and CD105 expression levels contribute to these osteopontential cell differences, that is, higher IGF2 expression levels and lower CD105 expression levels were associated with the increased osteogenic potential of SHED as compared to hASCs. The molecular mechanisms associated with the diferent expression levels of IGF2 and CD105 in these cells were also investigated. Despite the advantages of adult MSCs they can exhibit drawbacks such as restricted self-renewal and limited cell amounts. Induced Pluripotent Stem Cells (iPSC) technology has emerged as an alternative cell source, as they provide more homogeneous cellular populations with prolonged self-renewal and higher plasticity. We verified that the OD of MSC-like iPSC differs from MSCs and it depends on the iPSCs originating cellular source. Comparative in vitro osteogenesis analysis showed higher osteogenic potential in MSC-like cells derived from iPS-SHED when compared with MSC-like cells from iPS-FIB and SHED. iPSCs can be also used as a tool to model genetic disorders. We have thus proposed to verify if it could be possible to in vitro model Treacher-Collins syndrome, a condition with deficient craniofacial bone development. We have compared the effects of pathogenic mutations in TCOF1 gene in cell proliferation, differentiation potential between MSCs, dermal fibroblasts, neural-crest like and MSC-like cells differentiated from iPSCs.TCS cells showed changes in cell properties anddysregulated expression of chondrogenesis markers during osteogenic and chondrogenic differentiation. In summary, the comparative analysis of stem cells of different sources allow us to identify markers that may facilitate osteogenesis and that it is possible to establish an in vitro model to Treacher-Collins syndromeO uso de células-tronco trata-se de uma abordagem terapêutica promissora para a engenharia de tecidos, devido à sua capacidade na regeneração de tecidos, e para modelamento in vitro de distúrbios genéticos humanos, uma vez que fornece um abastecimento contínuo de células com potencial de diferenciação. Nosso estudo se propos a identificar moléculas e mecanismos que contribuem na otimização da osteogênese de células-tronco mesenquimais (MSCs). Para atingir nossos objetivos exploramos as diferenças no potencial osteogênico (PO) de MSCs de diferentes fontes. Observamos que MSCs de polpa de dente decíduo humano (SHED) apresentaram maior PO em comparação com as MSC derivadas de tecido adiposo humano (hASCs). Através de análise de microarray de expressão e cell sorting, demonstramos que os níveis de expressão de IGF2 e CD105 contribuem para as diferenças do PO, onde a maior expressão de IGF2 e menor expressão de CD105 estão associadas a maior PO em SHED quando comparado as hASCs. Também investigamos os mecanismos moleculares associados aos diferentes níveis de expressão de IGF2 E CD105 em ambas as fontes celulares. Apesar das vantagens, as MSCs podem apresentar pontos negativos como restrita auto-renovação e menor quantidade de células. Células-tronco pluripotentes induzidas (iPSC) surgem como uma fonte celular alternativa, proporcionando populações celulares homogêneas com auto-renovação prolongada e maior plasticidade. O PO de MSC-like iPSC difere de MSCs, e este potencial é dependente da fonte celular em que as iPSCs são obtidas. Análise comparativa de PO in vitro demonstrou maior osteogênse em células MSC-like derivadas de iPS-SHED quando comparada as células MSC-like de iPSCs-fibroblastos e SHED. iPSCs também podem ser utilizadas como ferramenta para investigar doenças genéticas humanas. Propomos a modelagem in vitro da síndrome de Treacher-Collins (TSC), doença que acomete as estruturas craniofaciais durante o desenvolvimento ósseo. Comparamos os efeitos de mutações patogênicas no gene TCOF1 na proliferação celular, potencial de diferenciação entre MSCs, fibroblastos dérmicos, neural-crest like e células MSC-like diferenciadas de iPSCs. Células de pacientes TCS exibiram alterações em propriedades celulares e na expressão de marcadores osteogênicos e condrogênicos. Em resumo, a análise comparativa de células-tronco de diferentes fontes permitiu a identificação de marcadores e mecanismos que podem facilitar a osteogênese e tambem demonstramos que é possível modelar in vitro a síndrome de Treacher-Collins
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Bernal, Sierra Yinth Andrea [Verfasser]. "Molecular markers of mechanoreceptors and potential molecules for gating mechanotransduction / Yinth Andrea Bernal Sierra." Berlin : Freie Universität Berlin, 2013. http://d-nb.info/1045194972/34.
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Jung, Renata. "Identification of Molecular Markers for Marker-Assisted Selection of Malting Quality and Associated Traits in Barley." Diss., North Dakota State University, 2015. http://hdl.handle.net/10365/25241.
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Barley (Hordeum vulgare L.) is one of the most important cereal crops in North Dakota, which ranks second amongst all states for barley production in the United States. Barley is used for the production of malt, which is used for brewing beer. The malting and brewing industries set strict standards for malt quality; yet, determining malt quality of experimental barley lines is very expensive. For this reason, quality is typically determined at the latter stages of the breeding program, resulting in rejection of many genotypes after large investments for agronomic performance, disease resistance, and end-use quality evaluations have occurred. High quality malt cultivars must possess numerous genetically controlled characteristics. This limits the effectiveness of phenotypic selection for malt quality. The use of marker-assisted selection (MAS) may enable breeders to eliminate lines with undesirable traits earlier in the breeding process, reducing costs, and improving genetic gain. In spite of the large number of mapped QTLs, few examples exist in the literature in which QTL analysis and MAS have been applied to the genetic improvement of malting barley. This research was initiated to identify robust marker-trait associations for malting quality, disease resistance, and agronomic traits utilizing genome-wide association mapping of selected NDSU two-rowed lines. Our research successfully identified numerous marker-trait associations for the traits evaluated to be used for MAS to improve the North Dakota State University barley breeding program.American Malting Barley Association
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Bin, Kaderi Mohamed Arifin. "Assessment of Novel Molecular Prognostic Markers in Chronic Lymphocytic Leukemia." Doctoral thesis, Uppsala universitet, Hematologi och immunologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-110371.
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The clinical course of chronic lymphocytic leukemia (CLL) is highly heterogeneous, which has prompted the search for biomarkers that can predict prognosis in this disease. The IGHV gene mutation status and certain genomic aberrations have been identified as reliable prognostic markers of clinical outcome for this disorder. However, the search for more feasible prognostic markers in CLL is still being pursued. Recently, certain single nucleotide polymorphisms (SNPs) in the GNAS1, BCL2 and MDM2 genes and the RNA expression levels of the LPL, ZAP70, TCL1, CLLU1 and MCL1 genes were suggested as novel prognostic markers in CLL. In papers I-III, we performed genotyping analyses of the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms in 268-418 CLL patients and related the genotypes with clinical data. Association studies between the polymorphisms and established prognostic markers (i.e. IGHV mutation status, genomic aberrations, CD38 expression) were also performed. Our studies did not find any significant relationship between these SNPs with either clinical outcome or other known prognostic markers in CLL. In paper IV, we measured the RNA expression levels of LPL, ZAP70, TCL1, CLLU1 and MCL1 in 252 CLL cases and correlated these levels with clinical outcome. Here, we verified that high expression of all these RNA-based markers, except MCL1, were associated with an unfavourable prognosis. We also confirmed a close relationship between IGHV mutation status and the RNA-based markers, especially for LPL and CLLU1 expression. Among the RNA-based markers, multivariate analysis revealed LPL expression as the strongest independent prognostic marker for overall survival and time to treatment. Furthermore, the RNA-based markers could add further prognostic information to established markers in subgroups of patients, with LPL expression status giving the most significant results. In summary, data from papers I-III could not verify the GNAS1 T393C, BCL2 -938C>A and MDM2 SNP309 polymorphisms as prognostic markers in CLL. Future SNP markers must hence be confirmed in large, independent cohorts before being proposed as prognostic marker in CLL. In paper IV, we conclude that LPL expression appears to be the strongest among the RNA-based markers for CLL prognostication. Further efforts to standardize LPL quantification are required before it can be applied in the clinical laboratory to predict clinical outcome in this disease.
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Poulsen, David Malcolm Ernest. "Application of molecular markers to breeding barleys for disease resistance /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17378.pdf.
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Ponza, Pattareeya, and pattareeya pon@biotec or th. "Molecular markers of ecotoxicological interest in the rainbowfish Melanotaenia fluviatilis." RMIT University. Applied Science, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080102.121231.
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The Crimson-spotted rainbowfish (Melanotaenia fluviatilis) from the Murray-Darling basin of Australia is a common indicator species in Australian ecotoxicology. Biochemical changes have been investigated in this species, but not molecular markers of ecotoxicological interest. In this study genes of M. fluviatilis were isolated using a cDNA library and sequences analysed. Of 345 randomly selected clones, 94 shared similarity with 26 different genes in other organisms in public databases. Amongst these, reproductive genes coding for vitellogenin, retinol binding protein, sialyltransferase and zona pellucida protein were considered of interest in ecotoxicology. The vitellogenin gene was selected for study as it has been widely used as a molecular marker of exposure to 17â-estradiol (E2) in teleosts. Gene expression was examined via northern blot, RT-PCR and Real-Time PCR relative to the housekeeping gene (18S rRNA). The expression of vitellogenin mRNA was observed a t 12 hours post-exposure, peaked at 48 hours according to northern blot analysis; and cleared within 4 days, partly consistent with RT-PCR. However, Real-time PCR yielded an inconclusive result, probably due to differences between pooled and individual samples. Vitellogenin in blood plasma was confirmed by western blot, found to be significantly increased and retained in the plasma in fish treated with E2 compared to controls. It was concluded that vitellogenin mRNA is a molecular marker of exposure to 17â-estradiol in the rainbowfish, and could potentially be used as a marker of exposure to environmental estrogenic chemicals. Further investigations of the expression of genes in the cDNA library, could establish other molecular markers of ecotoxicological interest in M. fluviatilis.
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Tar'an, Bunyamin. "Development and application of molecular markers in common bean breeding." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0015/NQ47413.pdf.
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Luan, Shi-Lu. "Molecular epidemiology of Streptococcus agalactiae : mobile elements as genetic markers /." Doctoral thesis, Umeå : Umeå University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-877.
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Mazhar, Kehkashan. "Molecular genetic markers for selection and genome mapping in cattle." Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260797.
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Eastmond, Nigel C. "Molecular markers of adipose tissue function during the febrile response." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.320259.
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Fever has been shown to increase metabolic rate and there is evidence that there is an induction of heat production in brown adipose tissue (BAT). This thesis examines heat production in BAT during fever by measuring GDP-binding to BAT mitochondria and the gene expression of UCP and lipoprotein lipase (LPL). Rats were injected iv. with lipopolysaccharide (LPS; 10 μg/kg body weight) and developed a triphasic fever characterized by an initial decrease in core temperature. Ketoprofen (3 mg/kg body weight), an inhibitor of prostaglandin synthesis, attenuated the increases in core temperature throughout the response but had no effect on the initial hypothermia. Animals made febrile with LPS showed no increase in GDP-binding to BAT mitochondria when compared to saline controls. UCP mRNA and LPL mRNA levels in BAT were also unaffected by the fever. Acute cold exposure induced increases in all of the above parameters. Measurements of the quantity of ob mRNA and LPL mRNA in the WAT of febrile rats revealed no changes in the expression of either gene. Acute cold exposure decreased the levels of ob mRNA, with smaller, but statistically insignificant decreases in LPL mRNA. Genetically obese (fa/fa) Zucker rats and lean controls responded to iv. LPS (10 μg/kg body weight) with a fever characterized by an initial hypothermia. The obese rats had lower levels of UCP mRNA in BAT, but not LPL mRNA, than lean controls. In addition, levels of ob mRNA were considerably elevated in the obese variant but, surprisingly, these differences were not statistically significant. It is concluded that fever does not necessarily involve thermogenesis in BAT and, that changes in energy balance during fever are not manifested as changes in the expression of the ob gene in WAT.
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Laatio, L. (Liisa). "In search of new prognostic molecular markers in ovarian cancer." Doctoral thesis, Oulun yliopisto, 2012. http://urn.fi/urn:isbn:9789514298349.
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Abstract Ovarian cancer is the leading cause of death from gynaecological cancers in the Western world. Ovarian cancer comprises of tumours with distinct behaviour and individually different responses to chemotherapy, even within the same histology. Unfortunately, there are no molecular markers in clinical use to either distinguish between patients with better and worse prognosis or to predict individual chemosensitivity. The comprehension of the molecular effects of chemotherapeutic drugs is a prerequisite for finding predictive molecular factors for chemoresponse and prognosis. Some proteins in molecular pathways contributing to DNA damage response, angiogenesis and oxidative stress have been implicated in ovarian cancer prognosis. In this study, the responses in p53 pathway and among angiogenesis-related factors to chemotherapeutic drugs were analysed in ovarian cancer cell lines. In OVCAR-3 cells with mutated p53, cisplatin but not docetaxel induced p14ARF, an important regulator of p53, at mRNA and protein level. Cisplatin also significantly increased the mRNA expression of angiogenesis-related factors TSP-1, BMP-4, ET-1 and PlGF-2 while an equivalent dose of docetaxel had only minor effects. In clinical ovarian carcinomas, the expression of BMP-4, TSP-1 and CD105 as well as the marker of oxidative stress derived DNA damage, 8-OHdG, and peroxiredoxin antioxidants were analysed by immunohistochemistry. High expression of BMP-4 and cytoplasmic peroxiredoxin IV were associated with better prognosis, while high 8-OHdG expression associated with shorter survival. Explant cultures of fresh ovarian tumour tissue were used for the evaluation of individual responses of p53 and Hdm2 after in vitro treatments of the explant cultures by carboplatin or docetaxel. Major differences between the individual tumours were found, especially in the responses of p53 to carboplatin. The results of this study suggest, that BMP-4, 8-OHdG and peroxiredoxin IV may serve as prognostic markers in ovarian cancer. The differences shown in the molecular responses to platinum and taxane drugs may have value in tailoring individual chemotherapy. Also, fresh ovarian cancer tissue explant culture is worth further studies as a predictive method for analysing individual tumour responses for chemotherapeutic agentsTiivistelmä Munasarjasyöpä on suurinta kuolleisuutta aiheuttava gynekologinen syöpä läntisessä maailmassa. Munasarjakasvaimet eroavat toisistaan niin käyttäytymiseltään kuin yksilölliseltä sytostaattihoitovasteeltaan, jopa sama histologisen tyypin sisällä. Kliinisessä käytössä ei valitettavasti ole sellaisia molekulaarisia merkkiaineita, jotka erottaisivat toisistaan paremman ja huonomman ennusteen kasvaimet tai ennustaisivat yksilöllistä solunsalpaajaherkkyyttä. Hoitovastetta ja potilaan prognoosia ennustavien merkkiaineiden löytämisen edellytys on kemoterapian molekyylitason vaikutusten ymmärtäminen. DNA vaurion tunnistamiseen, angiogeneesiin ja oksidatiiviseen stressiin liittyvien vaikutusreittien joillakin proteiineilla on ehdotettu olevan ennusteellista merkitystä munasarjasyövässä. Tässä väitöskirjatyössä analysoitiin munasarjasyöpäsoluja käyttäen p53 vaikutusreitin ja eräiden angiogeneesiin liittyvien tekijöiden vasteita sytostaateille. Mutatoitunutta p53 proteiinia kantavissa OVCAR-3 soluissa sisplatiini, toisin kuin dosetakseli, indusoi p53 proteiinin tärkeää säätelijää, p14ARF:a sekä mRNA- että proteiinitasolla. Sisplatiini lisäsi merkittävästi myös usean angiogeneesiin liittyvän tekijän (TSP-1, BMP-4, ET-1 ja PlGF-2) mRNA:ta. Dosetakselin vaikutukset vastaavalla annoksella olivat vähäiset. Kliinisissä munasarjasyövissä BMP-4, TSP-1 ja CD105 sekä oksidatiivisen stressin aiheuttaman DNA-vaurion merkkiaineen, 8-OHdG:n sekä peroksiredoksiiniantioksidanttien ilmeneminen analysoitiin immunohistokemiallisesti. BMP-4:n ja sytoplasmisen peroksiredoksiini IV:n vahva ilmentyminen liittyivät parempaan ennusteeseen, kun taas 8-OHdG:n vahva ilmentyminen liittyi huonompaan elinajan ennusteeseen. Tuoreen munasarjasyöpäkudoksen eksplanttiviljelyn avulla selvitettiin p53 ja Hdm2 proteiinien vasteita syöpäkudoksen karboplatiini- tai dosetakseli-käsittelyille. Selkeitä yksilökohtaisia eroja havaittiin erityisesti karboplatiinin aiheuttamissa p53 vasteissa niin eri potilaiden kuin eri histologisten kasvaintyyppien välillä. Tämän väitöskirjatutkimuksen tulokset antavat viitteitä BMP-4:n, 8-OHdG:n ja peroksiredoksiinin mahdollisesta ennusteellisesta merkityksestä munasarjasyövässä. Erot platinayhdisteiden ja taksaanien välillä saattavat osoittautua merkittäviksi yksilöllisiä syövän hoitoja räätälöitäessä. Tuoreen munasarjasyöpäkudoksen eksplanttiviljelyn mahdollisuuksia yksilöllisten kasvainten hoitovasteiden ennustamisessa kannattaa selvittää jatkotutkimuksin
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Scullin, P. "Molecular markers of response to systemic therapy in prostate cancer." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.492490.
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Prostate cancer is a significant health problem worldwide. Glucocorticoids, including' dexamethasone have formed the backbone of treatment of androgenindependent disease for the past 50 years and are given with docetaxel in the only therapy with a proven survival benefit in this setting. This study explored the mecha'nism of dexamethasone action in the treatment of androgen-independent prostate cancer (AIPC). In the in vitro study' dexamethasone administration induced a suppression of NFKB transcriptional activity in AIPC cells, resulting in a decreased transcription . arid/or secretion of the pro-angiogenic factors interleukin-8 and VEGF. In addition, co-administration of dexamethasone attenuated the docetaxel-induced .- '..: .. AP-1 and NF-KB transcriptional activity and abrogated the IL-8 gene transcription . - - -- - ·L and secretion in these cells and endothelial cells. In a novel finding, addition of dexamethasone potentiated the pronounced anti-angiogenic activity of docetaxel as assessed by an in vitro angiogenesis assay. Since no modulation of docetaxel cytotoxicity in endothelial cells by addition of. dexamethasone was observed, these results suggest that dexamethasone contributes to the efficacy of docetaxel through reduction of the docetaxel-induced increase of pro-angiogenic factors both in prostate cancer and endothelial cells, which translates into inhibition of angiogenesis. In the clinical study, the PSA response rate was 63%. Serum IL-8 was elevated in all 11 oatients for whom data is available. However. at this interim analvsis Supplied by The British Library - 'The world's knowledge' I I, I ' serum IL-8 levels were not consistently modified following dexamethasone therapy. However, when IL-8 is analysed as a binary variable, low IL-8 is associated with a prolonged time to biochemical progression which does not reach statistical significance at this time. Similarly, CRP levels were not affected consistently by dexamethasone but baseline CRP was lower in patients who achieved a PSA response than in those who did not respond, though this difference was not statistically significant.
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Potter, Tara. "AFLP markers linked to Fusarium head blight resistance in Triticum aestivum." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6321.
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In this study, AFLP technology was used to find markers linked to genes controlling Fusarium head blight (FHB) resistance in Triticum aestivum L. FHB is a disease of cereal crops that results in reduced wheat yields, discoloured, shrivelled kernels, mycotoxin accumulation, and reduced seed and grain quality. Since resistance mechanisms in wheat are complex, often being confounded by environmental effects, and there is high genotypic variance for resistance, molecular markers closely linked to FHB resistance would help in the screening of resistant germplasm. Candidate markers for resistance that were found among three varieties of wheat, two being susceptible to FHB ('Karena' and 'AC Cartier') and one being resistant to FHB (FHB 148), were followed into double haploid (DH) F2 from crosses between each of the susceptible varieties and the resistant variety. These DH lines were evaluated for resistance after inoculation with F. graminearum and MAXR linear regression was done to determine whether any of the candidate markers could explain the variation in phenotype. In the 'Karena'/FHB 148 DH lines, 67% of the polymorphisms segregated in a 1:1 Mendelian fashion (p ≥ 0.05), while 50% segregated 1:1 in the 'AC Cartier'/FHB 148 DH lines (p ≥ 0.05). In the 'Karena'/FHB 148 population, 35% of the variation in the FHB resistance phenotype was explained by two markers (p ≤ 0.05), while in the 'AC Cartier'/FHB 148 population, two markers explained 29% of the variation in phenotype (p ≤ 0.05). Cloning and sequencing of these markers would be useful in the development of cultivars resistant to FHB by marker assisted selection.
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Boutilier, Kim. "Isolation and characterization of molecular markers for Brassica napus microspore embryogenesis." Thesis, University of Ottawa (Canada), 1994. http://hdl.handle.net/10393/6474.
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Brassica napus microspores can be diverted from pollen development toward haploid embryo formation in culture by subjecting them to a heat stress treatment. This switch in developmental pathways has been shown to be accompanied by the induction of high levels of napin seed storage protein gene expression (DeMoor, 1992). Specific members of the napin multigene family that were expressed at this time were cloned from a cDNA library prepared from microspores that had been induced to undergo embryogenesis. The majority of napin clones represented three members (BnmNAP2, BnmNAP3 and BnmNAP4) that, along with a previously isolated napin genomic clone (BngNAP1), are members of the highly conserved BnmNAP subfamily of napin genes. DNA gel blot analysis, using a subfamily-specific probe, suggested that this subfamily may consist of up to 5 members. RNA gel blot analysis, also using the subfamily-specific probe, indicated that the BnmNAP subfamily was also expressed during embryo development. BnmNAP mRNA was detected as early as the globular stage of development in microsporic embryos, but not until the late torpedo/early cotyledon stage of development in zygotic embryos. A BngNAP1 promoter-$\beta$-glucuronidase (GUS) gene fusion was introduced into B. napus and Nicotiana tabacum (tobacco) plants in order to examine the spatial and temporal pattern of expression of one member of the BnmNAP subfamily. The BngNAP1-GUS construct was shown to be highly expressed in microspores that had been induced to undergo embryogenesis, but was not expressed in microspores continuing pollen development in culture. Furthermore, BngNAP1-directed GUS activity appeared to be predominantly localized in those microspores that have been shown to have the greatest potential to form embryos in culture. Fluorogenic and histochemical analysis of developing microsporic and zygotic embryos of B. napus indicated that the BngNAP1-GUS fusion was expressed as early as the globular stage of development. GUS activity was first detected in the micropylar region of the future embryonic axis and continued to spread upward during subsequent stages of development. In tobacco, GUS activity was first detected in the endosperm of seeds containing globular stage embryos. GUS activity did not begin to accumulate in tobacco embryos until the early heart stage of development, where it appeared as a band in the middle of the embryo, just under the lobes of the emerging cotyledons. This activity continued to spread outward in both directions as development proceeded. Thus the timing, but not the spatial localization, of BngNAP1-directed GUS expression was maintained in transgenic tobacco.
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Zeisset, Inga. "Molecular ecology of North European water frogs." Thesis, University of Sussex, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326908.
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Montenegro, Raquel Carvalho. "Preliminar study of the expression of molecular markers in patients with stomach cancer, in Ceara State." Universidade Federal do CearÃ, 2003. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=12.
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CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorIn search for a better understanding of the biology of tumors, molecular markers related to proliferation, resistance and apoptosis have been intensively studied in the different types of cancer. These markers can help on the elucidation of more specific therapeutic targets for the treatment of various tumors. It was observed that stomach cancer is the second most frequent cause of death in the world. In Brazil, this tumor is among the five major causes of death by cancer and the adenocarcinomas are held responsible for about 95% of all cases. For that matter, the expression of KI-67, PCNA, p53, bcl-2 and c-myc were evaluated independently and in a combined form in stomach adenocarcinomas. Thus, KI-67 and PCNA were confronted in order to determine which one would pose as a better cellular proliferation marker. Finally, a DNA extraction tecnique using CTAB was implemented on tumor tissue as well as the molecular analysis of the p53 gene by SSCP. The positive results were compared with those obtained by the imonohistochemistry analysis. The tumors were collected in surgical procedure, processed and classified histopathologically. The markers were detected by the imunohistochemical method SABP. The DNA was extracted by the CTAB method and the exons 5, 7 and 8/9 of the p53 gene analyzed by SABP. Some of the samples were obtained from biopsy arquives. The age range of the patients was between 61 and 70 years, with 48,1% of the tumors presenting an intestinal origin, 40,7% were diffuse and the other 11,2% were mixed. According to the location, 50% of the tumors were found to be proximal. 41,1% of the tumors were found to be in a low stage (I â IIIA), 44,8% in a high stage (IIIB â IV) and 13,8% were not staged. The imunohistochemical results indicated that KI-67 is the best marker to estimate cellular proliferation in stomach adenocarcinomas. In an independent manner, the tumors showed an 89,3% positivity for KI-67, 62,5% for PCNA, 50% for p53, 60,7% for bcl-2 e 66,7% for c-myc. According to the staging, the difference was significant only to p53 (p = 0,02), with a 66,7% positivity to the tumors in low stage and 16,7% for the ones on a high stage. When evaluated in a combined form, the associations of KI-67+/p53- (p=0,012) (66,67%) and c-myc+/p53- (p=0,02) (63,64%) both for the high stage tumors, were found to be significant. The DNA extraction technique applied to the tumor tissue was found to be satisfactory. For the SSCP analyses, five patients had mutation on the exon 5 (3) and on the exon 7 (2). Based on that, we may conclude that KI-67 is the best marker to access the proliferation of the stomach adenocarcinomas and that there are two proliferation activation pathways: one being dependent and the other independent of the p53 gene.
Na busca de um melhor entendimento da biologia dos tumores, marcadores moleculares relacionados à proliferaÃÃo, resistÃncia e apoptose tÃm sido intensamente pesquisados nos diferentes tipos de cÃncer. Estes marcadores podem auxiliar no estudo de alvos terapÃuticos mais especÃficos para cada tipo de tumor. O cÃncer de estÃmago à a segunda causa de Ãbito mais observado no mundo. No Brasil, este tumor està entre as cinco localizaÃÃes primÃrias mais comuns de Ãbitos por cÃncer, sendo os adenocarcinomas responsÃveis por 95% dos casos. Dessa forma, foi avaliada a expressÃo dos marcadores KI-67, PCNA, p53, bcl-2 e c-myc de forma independente e combinada em adenocarcinomas gÃstricos. TambÃm foi avaliado qual dos marcadores, KI-67 ou PCNA, era mais indicado para acessar a proliferaÃÃo celular. AlÃm disso, foi implantada a tÃcnica de extraÃÃo de DNA de tecido tumoral com CTAB e anÃlise molecular pelo SSCP do gene p53, sendo os resultados positivos comparados com os resultados da imunohistoquÃmica. Os tumores foram coletados em cirurgia, processados e classificados histopatologicamente. Os marcadores foram detectados pelo mÃtodo de imunohistoquÃmica SABP. Foi realizada a extraÃÃo de DNA pelo mÃtodo do CTAB, sendo os Ãxons 5, 7 e 8/9 do gene p53 analisados por SSCP. Algumas amostras foram obtidas de arquivo de biopsia. A faixa etÃria dos pacientes encontrava-se entre 61 e 70 anos de idade, com 48,1% dos tumores do tipo intestinal, 40,7% difusos e 11,2% mistos e com 50% localizados no sÃtio proximal. Em relaÃÃo ao estadiamento, 41,4% dos tumores apresentavam-se no grau baixo (I â IIIA), 44,8% no altorisco (IIIB â IV) e 13,8% sem estadiamento. De acordo com os achados imunohistoquÃmicos, os resultados sugerem que o marcador mais indicado para estimar a proliferaÃÃo celular nos adenocarcinomas gÃstricos à o KI-67. De forma independente os tumores apresentaram positividade em 89,3% para KI-67, 62,5% para PCNA, 50% para p53, 60,7% para bcl-2 e 66,7% e para c-myc. De acordo com o estadiamento, a diferenÃa foi significativa apenas para p53 (p = 0,02), com positividade de 66,7% nos tumores de baixo risco (I â IIIA) e 16,7% nos de altorisco. Quando avaliadas de forma combinada, as associaÃÃes significativas foram entre KI-67+/p53- (p=0,012) nos tumores de alto risco (66,67%) e c-myc+/p53- (p=0,02) tambÃm nos tumores de altorisco (63,64%). A tÃcnica aplicada para a extraÃÃo do DNA do tecido tumoral foi satisfatÃria. Para o SSCP, cinco pacientes apresentaram mutaÃÃo para o Ãxon 5 (3) e Ãxon 7 (2). Com isso, concluÃmos que o marcador mais indicado para acessar a proliferaÃÃo à o KI-67 e que existem duas vias de ativaÃÃo da proliferaÃÃo nos adenocarcinomas gÃstricos: uma dependente de p53 e outra independente de p53.
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Costa, Mónica Isabel Encarnação. "MHC-class I markers in non-alcoholic steatohepatitis." Master's thesis, Universidade de Aveiro, 2009. http://hdl.handle.net/10773/8797.
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Mestrado em Biologia Molecular e CelularO Fígado é o principal órgão regulador do metabolismo do ferro. Distúrbios relacionados com a sobrecarga de ferro podem ser devido a factores genéticos, como na HH com mutações conhecidas para o gene HFE, mas também associados a doença hepática crónica, como a NASH. Vários estudos relatam uma elevada frequência das mutações do gene HFE em pacientes com NASH. Do modelo genético e imunológico da HH, sabe-se que estes doentes têm um haplótipo conservado na região MHC que está associado com o número de células CD8 + T. Os indivíduos que têm baixos números de linfócitos T CD8 +, acumulam mais ferro no tecido hepático do que os têm elevado número de linfócitos CD8+ T. A partir destes pressupostos, questionamos se este efeito é também observado em pacientes com NASH e se a região MHC, utilizando os marcadores genéticos do modelo da HH, teria qualquer impacto na gravidade da doença. Foram analisados dados clínicos, imunológicos e histopatológicos de 59 pacientes com NASH. Pacientes com NASH foram genotipados para oito marcadores genéticos na região MHC correlacionados com o número de células CD8 + T (HLA-A, B e C; PGBD1; ZNF193 e HFE) e dois perto do HLA-A: RS7240078 e RS4713207. Controlos (264 indivíduos) foram utilizados para a comparação das frequências de todos os alelos, excepto para PGBD1 e ZNF193 onde um subgrupo (n = 56) foi usado. Não foram observadas diferenças estatisticamente significativas entre NASH e controlos para os marcadores genéticos e dados imunológicos. Foi encontrada uma associação entre números de linfócitos CD8 + T com fibrose e inflamação, sendo estas variáveis inversamente correlacionados. Os alelos HLA-A33 e HLA-A29 foram encontrados em dois haplótipos conservados na região definida pelos marcadores. O haplótipo contendo o HLA-A 33 encontra-se associado à presença de fibrose simultaneamente com uma baixa média de células CD8 + enquanto os indivíduos com o haplótipo do HLA-A 29 não desenvolviam fibrose e tinham linfócitos CD8+T mais elevados. Os resultados demonstram que o perfil imunológico dos NASH não reflecte o mesmo padrão da HH. Este facto pode ser devido à condição inflamatória dos NASH, porque as células CD8+ T à periferia não reflectem o que ocorre nos tecidos como é observado no modelo da HH.
Liver is the main organ in regulation of iron metabolism. Disorders of iron overload can be due to genetic factors, as in HH associated with the HFE gene mutations, and also associated with chronic liver disease, as in NASH. Several studies report a high frequency of HFE mutations in NASH patients. From HH genetic and immunological model it is known that a conserved haplotype in the MHC region is associated with CD8+T cell numbers. Individuals that have low CD8+T cell numbers have more iron accumulated in liver tissue, than individuals with high CD8+T cells. From these assumptions, we questioned if this effect is also seen in NASH patients and if the MHC region, using the genetic markers of HH, would have any impact in disease severity. Clinical, immunological and histopathological data from 59 NASH patients were analyzed. NASH patients were genotyped for eight genetic markers of the MHC region correlated with CD8+T cell numbers (HLA –A, B and C; PGBD1; ZNF193; HFE; RS7240078 and RS4713207. Controls (264 individuals) were used for comparing frequencies of all genes except for PGBD1 and ZNF193 where a subgroup (n=56) was used. No statistically significant differences were observed between NASH and controls for the genetic markers and immunological data. A negative association was found between CD8+T cell numbers and both fibrosis and inflammation. Two conserved haplotype were found with HLA-A33 and HLA-A29. HLA-A33 haplotype was found associated with the presence of fibrosis and low CD8+T cells average while haplotype carrying HLA-A*29 had less fibrosis and high CD8+T cells. In conclusion, the results show that immunological profile in NASH patients do not reflect the same picture as in HH. This may be due to a different distribution of lymphocytes cells between blood and tissues given the inflammatory condition in NASH.
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Callak, Kirisozu Asude. "Molecular Characterization Of Blumeria Graminis F. Sp. Hordei Using Aflp Markers." Master's thesis, METU, 2009. http://etd.lib.metu.edu.tr/upload/3/12611153/index.pdf.
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Blumeria graiminis f. sp. hordei (powdery mildew) is an obligate biotroph infecting hordeum vulgare (barley). It is one of the most devastating pathogens of barley, decreasing barley yield in great extent. In order to decrease barley loss, numerous studies are being conducted for overcoming the disease from the sides of both pathogen and host. However the pathogen is evolving very rapidly preventing the effective use of pesticides such as fungisides or development of resistant barley varieties by crossing race-specific resistance varieties, varieties having R genes, with susceptible but high yield producing varieties. In order to understand the mechanism of pathogen-host interactions, and producing enduring solutions for the problem of yield loss in barley molecular tools need to be used.
In this thesis study, Amplified Fragment Length Polymorphism (AFLP) molecular marker method is used in order to reveal the molecular characterization of Turkish Blumeria graminis f. sp. hordei varieties collected from Çukurova region in Turkey. Thirty-nine samples were analyzed with eigth universal races, of which virulence genes are studied. AFLP studies were conducted on LI-COR 4300 DNA Analyzer system. Bioinformatics analysis was performed with NTSYS program. By the help of this Numerical Taxonomic System, similarity, dissimilarity, clustering, dendograms, two-dimensional scatter plots, and three-dimensional perspective plots were obtained. By the light of these analyses Turkish Blumeria graminis f. sp. hordei varieties together with universal races are grouped into three clusteres. In conclusion, studying Turkish Blumeria graminis f. sp. hordei isolates and comparing them with universal races is a unique study in terms of characterizing the Turkish Bgh isolates for the first time, and can be used as a frontier study for studying Resistance genes, by reverse genetic tools.