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Genetic modification of lettuce for resistance to lettuce necrotic yellow virusCampbell, P. Unknown Date (has links)
No description available.
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Discovery of novel downstream target genes regulated by the hedgehog pathwayIngram, W. J. Unknown Date (has links)
No description available.
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Which postman delivers the RNA? Trans-acting factors in mRNA localisationSnee, Mark James Unknown Date (has links)
No description available.
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Discovery of novel downstream target genes regulated by the hedgehog pathwayIngram, W. J. Unknown Date (has links)
No description available.
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Post-transcriptional regulation of BRCA1: Investigation of the roles of RNA-binding proteins and cis-acting elements in the 3untranslated regionSaunus, Jodi Marie Unknown Date (has links)
BRCA1 is a breast cancer susceptibility gene that is down-regulated in the majority of cases of sporadic breast cancer. Accordingly, there is considerable interest in the mechanisms that regulate normal expression of BRCA1, with a view to elucidating how this could be disrupted in breast cancer. In tumours with reduced BRCA1 protein expression, there can be a concomitant reduction in mRNA level to variable degrees, or no change in mRNA level, suggesting that disruption of multiple different regulatory processes may contribute to BRCA1 down-regulation. Despite this, efforts to date have chiefly focussed on transcriptional and epigenetic regulation of the gene, whilst post-transcriptional processes that regulate the dynamics of the BRCA1 transcript, such as decay, localisation and translation efficiency, are poorly understood. Post-transcriptional regulatory pathways are critical for sustaining normal cellular physiology, as evidenced by many examples where disruption of these processes results in disease, including cancer. Regulation of gene expression at this level is often mediated by RNA-binding proteins that recognise specific cis-acting sequence motifs in the untranslated regions (UTRs) of certain messenger RNAs, and recruit, or shield them from macromolecular complexes involved in RNA metabolism, such as the translation apparatus, exosome, and subcellular transport particles. This thesis is centred on investigating post-transcriptional regulation of BRCA1. Others have shown that expression of the transcript and protein is regulated throughout the mammalian cell division cycle. Results presented in this thesis suggest that changes in mRNA stability may contribute to cell cycle-dependent expression of BRCA1, and therefore that post-transcriptional regulation of BRCA1 is a biologically-relevant phenomenon. To begin to address the molecular mechanisms involved in regulation of BRCA1 mRNA decay, and possibly other post-transcriptional regulatory processes, the 3UTR of BRCA1, which had not been previously characterised, was analysed for functional regulatory motifs using a combination of bioinformatics, reporter assays and RNA-proteinbinding analysis. An evolutionarily-conserved 3UTR subsequence was identified which contains sequence elements capable of regulating reporter activity, and forming complexes with multiple proteins from human epithelial cell lines. Some of these elements have been previously characterised in the context of other genes, including a Hu-antigen R (HuR)-binding motif, adenosine-uridine (AU)- rich sequences and a differentiation control element (DICE). Experiments were also conducted to determine the identities of the RNA-binding proteins detected using an RNA probe containing the 3UTR elements. A preliminary screen of a small group of RNA-binding proteins with previously-characterised roles in 3UTR-mediated post-transcriptional gene regulation identified HuR as a negative regulator of BRCA1 protein expression. Interestingly, HuR is over-expressed in breast cancer. Evidence presented in this thesis suggests that the mechanism of HuR-mediated down-regulation of BRCA1 involves direct binding of HuR to the BRCA1 3UTR, and no changes to mRNA stability or abundance. Finally, proteomics-based analysis of protein extracts enriched with BRCA1 3UTR RNA-binding proteins yielded several interesting candidates with previously-reported RNA-binding and/or post-transcriptional regulatory activities, including Far upstream element-binding protein 1 (FBP1), Glyceraldehyde-3-phosphate dehydrogenase (GAPD) and Heat-shock protein 27 (HSP27). This thesis addresses a clear deficiency in the literature concerning regulation of BRCA1, and contributes to our general understanding of the molecular mechanisms controlling gene expression in mammalian cells. Additionally, the finding that RNA-binding proteins that are over-expressed in breast cancer can negatively regulate BRCA1 expression constitutes important groundwork for identifying potential novel breast cancer therapeutics in the future.
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Post-transcriptional regulation of BRCA1: Investigation of the roles of RNA-binding proteins and cis-acting elements in the 3untranslated regionSaunus, Jodi Marie Unknown Date (has links)
BRCA1 is a breast cancer susceptibility gene that is down-regulated in the majority of cases of sporadic breast cancer. Accordingly, there is considerable interest in the mechanisms that regulate normal expression of BRCA1, with a view to elucidating how this could be disrupted in breast cancer. In tumours with reduced BRCA1 protein expression, there can be a concomitant reduction in mRNA level to variable degrees, or no change in mRNA level, suggesting that disruption of multiple different regulatory processes may contribute to BRCA1 down-regulation. Despite this, efforts to date have chiefly focussed on transcriptional and epigenetic regulation of the gene, whilst post-transcriptional processes that regulate the dynamics of the BRCA1 transcript, such as decay, localisation and translation efficiency, are poorly understood. Post-transcriptional regulatory pathways are critical for sustaining normal cellular physiology, as evidenced by many examples where disruption of these processes results in disease, including cancer. Regulation of gene expression at this level is often mediated by RNA-binding proteins that recognise specific cis-acting sequence motifs in the untranslated regions (UTRs) of certain messenger RNAs, and recruit, or shield them from macromolecular complexes involved in RNA metabolism, such as the translation apparatus, exosome, and subcellular transport particles. This thesis is centred on investigating post-transcriptional regulation of BRCA1. Others have shown that expression of the transcript and protein is regulated throughout the mammalian cell division cycle. Results presented in this thesis suggest that changes in mRNA stability may contribute to cell cycle-dependent expression of BRCA1, and therefore that post-transcriptional regulation of BRCA1 is a biologically-relevant phenomenon. To begin to address the molecular mechanisms involved in regulation of BRCA1 mRNA decay, and possibly other post-transcriptional regulatory processes, the 3UTR of BRCA1, which had not been previously characterised, was analysed for functional regulatory motifs using a combination of bioinformatics, reporter assays and RNA-proteinbinding analysis. An evolutionarily-conserved 3UTR subsequence was identified which contains sequence elements capable of regulating reporter activity, and forming complexes with multiple proteins from human epithelial cell lines. Some of these elements have been previously characterised in the context of other genes, including a Hu-antigen R (HuR)-binding motif, adenosine-uridine (AU)- rich sequences and a differentiation control element (DICE). Experiments were also conducted to determine the identities of the RNA-binding proteins detected using an RNA probe containing the 3UTR elements. A preliminary screen of a small group of RNA-binding proteins with previously-characterised roles in 3UTR-mediated post-transcriptional gene regulation identified HuR as a negative regulator of BRCA1 protein expression. Interestingly, HuR is over-expressed in breast cancer. Evidence presented in this thesis suggests that the mechanism of HuR-mediated down-regulation of BRCA1 involves direct binding of HuR to the BRCA1 3UTR, and no changes to mRNA stability or abundance. Finally, proteomics-based analysis of protein extracts enriched with BRCA1 3UTR RNA-binding proteins yielded several interesting candidates with previously-reported RNA-binding and/or post-transcriptional regulatory activities, including Far upstream element-binding protein 1 (FBP1), Glyceraldehyde-3-phosphate dehydrogenase (GAPD) and Heat-shock protein 27 (HSP27). This thesis addresses a clear deficiency in the literature concerning regulation of BRCA1, and contributes to our general understanding of the molecular mechanisms controlling gene expression in mammalian cells. Additionally, the finding that RNA-binding proteins that are over-expressed in breast cancer can negatively regulate BRCA1 expression constitutes important groundwork for identifying potential novel breast cancer therapeutics in the future.
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Post-transcriptional regulation of BRCA1: Investigation of the roles of RNA-binding proteins and cis-acting elements in the 3untranslated regionSaunus, Jodi Marie Unknown Date (has links)
BRCA1 is a breast cancer susceptibility gene that is down-regulated in the majority of cases of sporadic breast cancer. Accordingly, there is considerable interest in the mechanisms that regulate normal expression of BRCA1, with a view to elucidating how this could be disrupted in breast cancer. In tumours with reduced BRCA1 protein expression, there can be a concomitant reduction in mRNA level to variable degrees, or no change in mRNA level, suggesting that disruption of multiple different regulatory processes may contribute to BRCA1 down-regulation. Despite this, efforts to date have chiefly focussed on transcriptional and epigenetic regulation of the gene, whilst post-transcriptional processes that regulate the dynamics of the BRCA1 transcript, such as decay, localisation and translation efficiency, are poorly understood. Post-transcriptional regulatory pathways are critical for sustaining normal cellular physiology, as evidenced by many examples where disruption of these processes results in disease, including cancer. Regulation of gene expression at this level is often mediated by RNA-binding proteins that recognise specific cis-acting sequence motifs in the untranslated regions (UTRs) of certain messenger RNAs, and recruit, or shield them from macromolecular complexes involved in RNA metabolism, such as the translation apparatus, exosome, and subcellular transport particles. This thesis is centred on investigating post-transcriptional regulation of BRCA1. Others have shown that expression of the transcript and protein is regulated throughout the mammalian cell division cycle. Results presented in this thesis suggest that changes in mRNA stability may contribute to cell cycle-dependent expression of BRCA1, and therefore that post-transcriptional regulation of BRCA1 is a biologically-relevant phenomenon. To begin to address the molecular mechanisms involved in regulation of BRCA1 mRNA decay, and possibly other post-transcriptional regulatory processes, the 3UTR of BRCA1, which had not been previously characterised, was analysed for functional regulatory motifs using a combination of bioinformatics, reporter assays and RNA-proteinbinding analysis. An evolutionarily-conserved 3UTR subsequence was identified which contains sequence elements capable of regulating reporter activity, and forming complexes with multiple proteins from human epithelial cell lines. Some of these elements have been previously characterised in the context of other genes, including a Hu-antigen R (HuR)-binding motif, adenosine-uridine (AU)- rich sequences and a differentiation control element (DICE). Experiments were also conducted to determine the identities of the RNA-binding proteins detected using an RNA probe containing the 3UTR elements. A preliminary screen of a small group of RNA-binding proteins with previously-characterised roles in 3UTR-mediated post-transcriptional gene regulation identified HuR as a negative regulator of BRCA1 protein expression. Interestingly, HuR is over-expressed in breast cancer. Evidence presented in this thesis suggests that the mechanism of HuR-mediated down-regulation of BRCA1 involves direct binding of HuR to the BRCA1 3UTR, and no changes to mRNA stability or abundance. Finally, proteomics-based analysis of protein extracts enriched with BRCA1 3UTR RNA-binding proteins yielded several interesting candidates with previously-reported RNA-binding and/or post-transcriptional regulatory activities, including Far upstream element-binding protein 1 (FBP1), Glyceraldehyde-3-phosphate dehydrogenase (GAPD) and Heat-shock protein 27 (HSP27). This thesis addresses a clear deficiency in the literature concerning regulation of BRCA1, and contributes to our general understanding of the molecular mechanisms controlling gene expression in mammalian cells. Additionally, the finding that RNA-binding proteins that are over-expressed in breast cancer can negatively regulate BRCA1 expression constitutes important groundwork for identifying potential novel breast cancer therapeutics in the future.
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Which postman delivers the RNA? Trans-acting factors in mRNA localisationSnee, Mark James Unknown Date (has links)
No description available.
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Post-transcriptional regulation of BRCA1: Investigation of the roles of RNA-binding proteins and cis-acting elements in the 3untranslated regionSaunus, Jodi Marie Unknown Date (has links)
BRCA1 is a breast cancer susceptibility gene that is down-regulated in the majority of cases of sporadic breast cancer. Accordingly, there is considerable interest in the mechanisms that regulate normal expression of BRCA1, with a view to elucidating how this could be disrupted in breast cancer. In tumours with reduced BRCA1 protein expression, there can be a concomitant reduction in mRNA level to variable degrees, or no change in mRNA level, suggesting that disruption of multiple different regulatory processes may contribute to BRCA1 down-regulation. Despite this, efforts to date have chiefly focussed on transcriptional and epigenetic regulation of the gene, whilst post-transcriptional processes that regulate the dynamics of the BRCA1 transcript, such as decay, localisation and translation efficiency, are poorly understood. Post-transcriptional regulatory pathways are critical for sustaining normal cellular physiology, as evidenced by many examples where disruption of these processes results in disease, including cancer. Regulation of gene expression at this level is often mediated by RNA-binding proteins that recognise specific cis-acting sequence motifs in the untranslated regions (UTRs) of certain messenger RNAs, and recruit, or shield them from macromolecular complexes involved in RNA metabolism, such as the translation apparatus, exosome, and subcellular transport particles. This thesis is centred on investigating post-transcriptional regulation of BRCA1. Others have shown that expression of the transcript and protein is regulated throughout the mammalian cell division cycle. Results presented in this thesis suggest that changes in mRNA stability may contribute to cell cycle-dependent expression of BRCA1, and therefore that post-transcriptional regulation of BRCA1 is a biologically-relevant phenomenon. To begin to address the molecular mechanisms involved in regulation of BRCA1 mRNA decay, and possibly other post-transcriptional regulatory processes, the 3UTR of BRCA1, which had not been previously characterised, was analysed for functional regulatory motifs using a combination of bioinformatics, reporter assays and RNA-proteinbinding analysis. An evolutionarily-conserved 3UTR subsequence was identified which contains sequence elements capable of regulating reporter activity, and forming complexes with multiple proteins from human epithelial cell lines. Some of these elements have been previously characterised in the context of other genes, including a Hu-antigen R (HuR)-binding motif, adenosine-uridine (AU)- rich sequences and a differentiation control element (DICE). Experiments were also conducted to determine the identities of the RNA-binding proteins detected using an RNA probe containing the 3UTR elements. A preliminary screen of a small group of RNA-binding proteins with previously-characterised roles in 3UTR-mediated post-transcriptional gene regulation identified HuR as a negative regulator of BRCA1 protein expression. Interestingly, HuR is over-expressed in breast cancer. Evidence presented in this thesis suggests that the mechanism of HuR-mediated down-regulation of BRCA1 involves direct binding of HuR to the BRCA1 3UTR, and no changes to mRNA stability or abundance. Finally, proteomics-based analysis of protein extracts enriched with BRCA1 3UTR RNA-binding proteins yielded several interesting candidates with previously-reported RNA-binding and/or post-transcriptional regulatory activities, including Far upstream element-binding protein 1 (FBP1), Glyceraldehyde-3-phosphate dehydrogenase (GAPD) and Heat-shock protein 27 (HSP27). This thesis addresses a clear deficiency in the literature concerning regulation of BRCA1, and contributes to our general understanding of the molecular mechanisms controlling gene expression in mammalian cells. Additionally, the finding that RNA-binding proteins that are over-expressed in breast cancer can negatively regulate BRCA1 expression constitutes important groundwork for identifying potential novel breast cancer therapeutics in the future.
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Taxonomy and Biology of benedeniine capsalid monogeneansDeveney, Marty R. Unknown Date (has links)
Abstract The Benedeniinae, the largest of nine capsalid subfamilies, includes genera with an aseptate, apapillate haptor and a pair of discrete testes. Eight of 13 nominal benedeniine genera, Benedenia Diesing, 1858 (the type genus); Allobenedenia Yamaguti, 1963; Allometabenedeniella Velasquez, 1982; Dioncopseudobenedenia Yamaguti, 1965; Lagenivaginopseudobenedenia Yamaguti, 1966; Oligoncobenedenia Yamaguti, 1965; Pseudallobenedenia Yamaguti, 1966 and Tareenia, Hussey, 1986 are revised using type material of most nominal species with observations for some species from new material. Allobenedenia and Allometabenedeniella are transferred to the Trochopodinae Price, 1936 emend. Sproston, 1946 because all valid species of both genera bear septa on the ventral haptor surface. Allobenedenia ishikawae (Goto, 1894) Yamaguti, 1963 is transferred to Benedenia because its haptor is aseptate. I recognize Menziesia Gibson, 1976, based on the form of the male copulatory organ and associated structures and include five species in it. Tareenia Hussey, 1986 is synonymised with Benedenia because characters used to differentiate the two genera do not indicate discontinuities at the generic level. Benedeniella Johnston, 1929, Calicobenedenia Kritsky and Fennessy, 1999 and Trimusculotrema Whittington and Barton, 1990 are considered to belong in Entobdellinae Bychowsky, 1957, pending further studies on that group. The anatomy of Calicobenedenia is outlined briefly; the other genera are not discussed here in detail. Lachishia n. g. is described, based on the structure of the male copulatory organ and a species is transferred to it from Dioncopseudobenedenia. I describe four new species of benedeniines from teleosts caught at Heron and Green Islands, Australia namely: Benedenia ernsti n. sp. from the gills of Symphorus nematophorus; Benedenia fieldsi n. sp. from the fins of Cephalopholis boenak, C. cyanostigma and C. miniatus; Benedenia haywardi n. sp. from the skin of S. nematophorus and Dioncopsudobenedenia ancoralis n. sp. from the gills of Siganus lineatus. Benedenia akaisaki Iwata, 1990 is synonymised with B. ovata (Goto, 1894) Johnston, 1929, B. kintoki Iwata, 1990 is synonymised with B. elongata (Yamaguti, 1968) Egorova, 1997, B. sargocentron Zhang, Yang and Liu, 2001 is synonymised with B. hawaiiensis Yamaguti, 1968 and Pseudallobenedenia arabica Timofeeva, 1995 is synonymised with P. opakapaka Yamaguti, 1966. Benedenia madai Ishii and Sawada, 1938, B. pagrosomi Ishii and Sawada, 1938 and Allobenedenia pedunculata Raju and Rao, 1980 are considered species inquirendae. I examined an outbreak in aquaculture of the pathogenic benedeniine, Neobenedenia melleni (MacCallum, 1927) Yamaguti, 1963 and report this species for the first time in Australia. I examined the pathogenesis caused by this parasite by histology of host tissue. Possible routes of introduction to the farm in question are investigated and studies are detailed that should be undertaken in Australia to manage future outbreaks of N. melleni. Capsalids usually colonise new hosts by an infective ciliated oncomiracidium. An experiment was conducted to ascertain whether cleaner fish Labroides dimidiatus could transfer adult skin-parasitic monogeneans from one host fish to another. I have shown that transmission of adult monogeneans between two individuals of Hemigymnus melapterus by cleaner fish can occur. In coral reef environments, frequent contact between unrelated hosts involved in cleaning interactions might create previously unsuspected evolutionary pressures. I discuss the implications of this discovery for host-specificity and lateral transmission of monogeneans. General biological studies of monogeneans are necessary to understand the evolution, pathology, epidemiology, phylogeny and taxonomy of these parasites. My study provides a taxonomic system which, when applied to other capsalid subfamilies, should help prevent errors and create a clear system of classification for the entire family.
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