Thèse--Neuchâtel. / "Bibliographie": p. 224-227.

Thesis (Ph. D.)--University of Oulu. / Includes bibliographical references.

Thesis (M.A.)--University of British Columbia, 2003. / Includes bibliographical references (leaves 98-103).

Thesis (B.A.)--University of Utah, 2005. / Includes bibliographical references (leaves 49-54). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (B.A.)--University of Utah, 2005. / Includes bibliographical references (leaves 49-54).

Despite their beneficial effects, concerns have been raised about the role of antimicrobial growth promoters (AGP) in the emergence of antibiotic resistant bacteria. This study evaluated the effects of approved AGP on the emergence of antibiotic resistance in commensal E. coli and foodborne pathogen Salmonella. A survey of antibiotic resistance levels in commercial broiler chicken farms in the Fraser Valley (B.C.) and an experimental feeding trial were conducted from May 2004 to February 2005 and May to November 2005, respectively. The latter examined the effects of ten AGP formulations (bambermycin, penicillin, salinomycin, bacitracin, combination of salinomycin and bacitracin, chlortetracycline, virginiamycin 11ppm, virginiamycin 22ppm, monensin and narasin) on bird performance as well. Multiple antibiotic resistant commensal E. coli and Salmonella carrying virulence genes were found at commercial broiler chicken farms and therefore may serve as reservoirs for these genes. There was no significant difference between feed formulations on the phenotypic or genotypic characteristics of the isolates, except for tetracycline resistance gene tet(B). In the experimental feeding trial, broiler chickens were fed a diet including or excluding AGP. Birds were sampled prior to and weekly during feeding of the control and the AGPP containing diets. Although not detected on day 0, E. coli increased after day 7 to more than 9.9 log10 CFU/g in ceca. Multi-drug resistant E. coli were isolated from birds fed the ten AGP containing diets as well as the control diet. Except for penicillin, none of the AGP containing diets significantly improved bird performance compared to the control diet (P>0.05). Good management practices can significantly improve broiler chickens performance and decrease the mortality rate. / Land and Food Systems, Faculty of / Graduate

The basic helix-loop-helix (bHLH) family oftranscription factors consists of proteins involved in cellular proliferation and differentiation. The HLH structure plays a key role in protein-protein dimerization and with the DNA target sites, referred to as E boxes containing the consensus DNA sequence CANNTG. One class of mammalian class I bHLH proteins includes products of the E2A gene, which result from alternative splicing (E12, E47, and ITF), E2-2 and HEB. E2A proteins have also been detected in most cell lines with high levels of expression in lymphoid- and pancreatic cells. It has also been demonstrated that E2A is required for B cell maturation, T cell development and has been shown to function as tumor suppressors. To date, an E2A-interacting bHLH transcription factor largely restricted to activated B lymphocytes, called ABF -1, was isolated using the two-hybrid system. ABF -1 is the only B cell restricted bHLH protein isolated. ABF-1/E2A heterodimers have been detected in B lymphocytes. In these studies, the mapping of the ABF-1 promoter and the critical 5' regulatory elements that control ABF-1 gene expression were analyzed through 5' deletional analysis. 5' -DNA flanking pieces of the promoter region were created through PCR and inserted into a promoterless cloning vector containing the firefly luciferase reporter gene. RT -PCR analysis and anchored PCR was utilized to demonstrate the transcriptional activity of the - promoter region of the ABF-1 gene. Transient transfections were completed to determine critical regulatory sequences. The promoter location was confirmed through computer analysis of the nucleotide sequence and deletional analysis.

Yes / DNA breaks at protein-coding sequences are well-established threats to tissue homeostasis and maintenance. They arise from the exposure to intracellular and environmental genotoxins, causing damage in one or two strands of the DNA. DNA breaks have been also reported in non-coding regulatory regions such as enhancers and promoters. They arise from essential cellular processes required for gene transcription, cell identity and function. One such process that has attracted recent attention is the oxidative demethylation of DNA and histones, which generates abasic sites and DNA single-strand breaks. Here, we discuss how oxidative DNA breaks at non-coding regulatory regions are generated and the recently reported role of NuMA (nuclear mitotic apparatus) protein in promoting transcription and repair at these regions.

by Abdrew Pang Kin Kwan & Chan Yiu Nin. / Thesis (M.B.A.)--Chinese University of Hong Kong, 1988. / Bibliography: leaves 104-106.

La transcription est une étape fondamentale dans l'expression des gènes. Cependant, elle reste incomplètement caractérisée dans les cellules vivantes. Pour mieux comprendre la dynamique de la transcription, notre laboratoire a amélioré le système de marquage d'ARN en utilisant la séquence codante pour MS2, facilement fusionnée avec le promoteur d'intérêt et inséré copie unique dans deux lignées cellulaires HeLa cellules. Cette construction permet une vue quantitative de la transcription, a l’échelle de la molécule unique, en temps réel. Nous avons trouvé que le VIH-1 est transcrit par des groupes de polymérases nominés convois. La transcription oscille de manière aléatoire avec des périodes actives (ON) et inactives (OFF) et est contrôlée indépendamment.Sur la base de cette découverte, nous avons étudié: (i) comment l'architecture de différents promoteurs de mammifères contrôle la cinétique transcriptionnelle; et (ii) le rôle du transactivateur transcriptionnel (Tat), le régulateur principal de la transcription du VIH-1, dans les cellules vivantes. Pour traiter ces questions, une nouvelle méthode de modélisation a été établi, combinant l'information des fluctuations transcriptionnelles avec différentes résolutions temporelles. Cela a donné une vue complète et précise du processus stochastique, décrit par le modèle de Markov. Cinq des six promoteurs de mammifères pourraient être définis par trois états, probablement contrôlés par des mécanismes différents. Le passage entre ces états est défini par les constantes de vitesse et l'écart entre eux pourrait potentiellement expliquer la différence dans la quantité d'ARN produit. De manière intéressante, nous avons constaté que les taux de passage entre les états inactifs et profondément silencieux sont la marque distinctive de différents promoteurs, suggérant que les événements cruciaux définissant les profils transcriptionnels sont en fait des événements pré-transcriptionnels.Pour étudier le rôle de Tat, des lignées cellulaires contenant un rapporteur du VIH-1 et une quantité différente de Tat ont été produites. Avec cette approche décrite ci-dessus, nous avons montré que Tat, précédemment caractérisé en tant qu'acteur dominant dans la libération de la polymérase en pause, agit longtemps avant que la transcription soit initiée. Ces résultats frappants apportent de nouvelles perspectives concernant la dynamique transcriptionnelle du VIH-1 contrôlée par Tat. / Transcription is a fundamental step in gene expression. However, it is incompletely characterized in single living cells. To address this question, our laboratory developed the improved RNA tagging system using MS2-binding protein that could easily be fused with the promoter of interest inserted in a single copy in HeLa cell lines. This construct allows quantitative, single molecule view of the transcription in a real time. We have found that HIV-1 is transcribed by groups of closely spaced polymerases referred as convoys. The transcription oscillates randomly between active (ON) and inactive (OFF) periods that are controlled independently.On the basis of this discovery, we further investigated: (i) how architecture of different mammalian promoters controls the transcriptional kinetics; and (ii) the role of transcriptional transactivator (Tat), the master regulator of in HIV-1 transcription in living cells. To address this, new pipeline for the quantification was established, combining the information of transcriptional fluctuations with different temporal resolutions. This gave the full and precise view of the stochastic switching, described by the Markov model. Five of six mammalian promoters could be defined by three states, probably controlled by different mechanisms. Switching between them is defined by the rate constants and the discrepancy among them could potentially explain the difference in the amount mRNA produced. Interestingly, we found that switching rates between inactive, deeply silent states are the hallmark of different promoters, suggesting that the crucial events defining the transcriptional profiles are in fact pre-transcriptional events.To address the role of Tat, cell lines containing HIV-1 reporter and different amounts of Tat were produced. With the above described approach, we found that Tat, previously characterized as dominant player in the release of the paused polymerase, actually acts long before the transcription is initiated. These striking results bring new insights of HIV-1 transcriptional dynamics controlled by Tat.