Thesis (Ph. D.)--University of Wisconsin--Madison, 1959. / Typescript. Abstracted in Dissertation abstracts, v. 19 (1959) no. 11, p. 2745-2746. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thèse (Ph. D.)--Université Laval, 2003. / Bibliogr.: f. 152-193. Publié aussi en version électronique.

Thesis (M.Sc. (Pharmacy)) - Rhodes University, 2007.

Made available in DSpace on 2014-10-09T12:23:19Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:35Z (GMT). No. of bitstreams: 1 01276.pdf: 2214172 bytes, checksum: e105537b579f510e386e4b8e27eb1ef6 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Biociencias, Universidade de Sao Paulo - IB/USP

Au cours du développement, les organismes croissent de façon harmonieuse suivant un programme génétique intrinsèque et en adaptation avec les conditions environnementales. Chaque tissu atteint une taille cible qui est proportionnelle à la taille finale des autres organes et à celle de l’organisme. Des expériences de régénération effectuées sur différents modèles animaux ont révélé que chaque organe possède un programme autonome de croissance. Ainsi, des mécanismes de coordination entre la croissance tissulaire et le programme de développement sont nécessaires afin d’assurer une régulation fine de l’allométrie avant le passage du stade juvénile au stade adulte fixant la taille finale du corps. Dilp8 (Drosophila Insulin Like Peptide 8) est une hormone analogue aux peptides de la famille des insulines/relaxines. Elle est produite par les tissus dont la croissance est lésée, en régénération ou néoplasique. dilp8 inhibe la production d’hormone stéroïde et retarde ainsi le passage à la forme adulte. Les mutants dilp8 présentent une augmentation du bruit développemental qui se traduit par une perte de la symétrie bilatérale des organes (asymétrie fluctuante FA). Ceci suggère un rôle de dilp8 dans la coordination de la croissance entre les organes. Au cours de ma thèse, j’ai pu montrer que la voie de signalisation Hippo, son activateur transcriptionnel Yorkie et son co-partenaire Scalloped régulent directement les niveaux transcriptionnels de dilp8 via un Hippo Responsive Element (HRE) présent dans le promoteur de dilp8. La voie Hippo joue un rôle clé dans le contrôle de la taille des organes en couplant les paramètres biomécaniques des tissus avec la prolifération cellulaire. / Growth of different body parts needs to be coordinated and scaled with the overall body size to give rise to adults of correct proportions. Since different organs follow autonomous growth programs, mechanisms must operate to ensure that each organ has reached an appropriate size before proceeding through developmental transitions. We recently identified Dilp8 (Drosophila insulin-like peptide 8) as a key hormone in coupling organ growth with animal maturation. Dilp8 is secreted from abnormally growing tissues and acts on the brain complex to delay pupariation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in coordinating organ growth and ensuring developmental stability. Identifying signals that control dilp8 expression is therefore likely to provide a better understanding of organ size assessment mechanisms. The Hippo tumour suppressor pathway plays a major function in restricting organ growth by promoting cell cycle exit and apoptosis. Hippo signalling is responsive to the mechanical forces operating in growing organs making it an ideal candidate for assessing organ size. Activation of the Hippo pathway restricts nuclear translocation of the transcriptional co-activator Yorkie (Yki), which together with its DNA-binding partner Scalloped (Sd), regulates downstream growth-promoting target genes. Using a molecular biology approach, we show that Yki/Sd directly regulate dilp8 expression through a Hpo Responsive Element (HRE) in the dilp8 promoter.

Made available in DSpace on 2014-10-09T12:23:19Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:57:35Z (GMT). No. of bitstreams: 1 01276.pdf: 2214172 bytes, checksum: e105537b579f510e386e4b8e27eb1ef6 (MD5) / Dissertacao (Mestrado) / IEA/D / Instituto de Biociencias, Universidade de Sao Paulo - IB/USP

Philosophiae Doctor - PhD / Plant natriuretic peptides (PNPs) are a novel class of extracellular, systemically mobile molecules that elicit a number of plant responses important in homeostasis and growth. Natriuretic peptides were first identified in vertebrates where they play a role in the regulation of salt and water balance. Subsequent experimental investigations have identified the presence of a natriuretic peptide hormone system in plants. While PNPs have been implicated in various physiological responses such as stomatal guard cell movements and regulation of net water uptake, its biological role has remained elusive. Here we have used co-expression and promoter content analysis tools to understand the biological role of the Arabidopsis thaliana PNP (AtPNP-A). The analysis of AtPNP-A and its co-expressed genes revealed that genes annotated as part of the systemic acquired resistance (SAR) pathway were over-represented, thus suggesting that AtPNP-A may function as a component of plant defense responses and specifically, SAR. The results further show that AtPNP-A shares many characteristics with pathogenesis related (PR) proteins in that its transcription is strongly induced in response to pathogen challenges, thus implying a newly described role for AtPNP-A in pathogen attack. Additional tissue expression analysis also indicated distinct localization of PNP activity in sepals and transcriptional meta-analysis showed that AtPNP-A may play a role in starch breakdown. Therefore, together with the finding that AtPNP-A plays a role in regulating phloem transport, we also hypothesize that AtPNP-A may play a role in phloem unloading in sepals to assist processes such as seed formation in plants. In plants, the second messenger, guanosine 3’,5’-cyclic monophosphate (cGMP) mediates a whole range of important processes including salinity tolerance, disease resistance, drought tolerance and responses to light. Since PNPs regulate water and salt homeostasis via a cGMP-dependent signaling pathways, it is thus important to analyse the transcriptome induced by the second messenger (cGMP) in Arabidopsis thaliana to give a better understanding of its mechanism of action. This study was also supplemented by the analysis of the gibberellic acid (GA) dependent transcriptome, since cGMP also plays a role its transcription pathway. This data analysis, together with promoter content investigation, revealed that genes upregulated after cGMP treatment and down-regulated in the GA insensitive mutant (ga1-3) were enriched with a GA response element (GARE), while no GARE enrichment were observed in genes up-regulated in the ga1-3 mutant. These findings suggest that GARE is indicative of GA-induced and cGMP-dependent transcriptional up-regulation. Gene ontology analysis confirmed previous reports that cGMP is involved in ion homeostasis and indicated that the transcriptional cGMP response is bi-polar in the sense that both genes up- and down-regulated in response to cGMP is involved in cation transport. Additionally, ab initio analysis of genes transcriptionally dependent on cGMP identified CHX8 as a hub gene and promoter content of CHX8 co-expressed genes show enrichment of the GARE motif. The fact that CHX8 has its highest expression levels during male gametogenesis and pollen tube growth, together with our findings, suggest that GA-induced and cGMP- dependent genes may play a key role in ion and water homeostasis in the male gametophyte. Finally, we propose that the type of analysis undertaken here can yield new insights into gene regulation networks and inform experimental strategies to unravel complex transcription regulatory systems under different developmental and stimulus specific conditions. / South Africa

Plant natriuretic peptides (PNP) are novel peptides which, like in vertebrates, have been shown to have a function associated with water and salt homeostasis. Two PNP-encoding genes have been identified and isolated from Arabidopsis thaliana, namely; AtPNP-A and AtPNP-B. In this study, the focus was on PNP-B, which has not been extensively studied. Bioinformatic analysis was done on the AtPNP-B gene. This included the bioinformatic study of its primary structure, secondary structure, tertiary structure, transcription factor binding sites (TFBS) and its relation to other known proteins. The AtPNP-B gene was shown to be a 510 bp long, including a predicted 138 bp intron. AtPNP-B was also shown to have some sequence similarity with AtPNP-A and CjBAp12. The TFBS for AtPNP-B and OsJPNP-B were compared and they comprised of TFBS that are related to water homeostasis and pathogenesis. This suggested two possible functions; water stress and homeostasis and a pathogenesis related function for PNP-B. Following bioinformatic analysis, the heterologous expression of the AtPNP-B was attempted to investigate whether the AtPNP-B gene encoded a functional protein and to determine the functional role of PNP-B. However, expression was unsuccessful. An evolutionary study was then carried out which revealed that there were some plants without the intron such as, rice, leafy spurge, oilseed rape, onion, poplar, sugar cane, sunflower and tobacco. These plants would therefore be used for expression and functional studies in the future. The evolutionary studies also revealed that PNP-B had a relationship with expansins and the endoglucanase family 45. Other PNP-B related molecules were also obtained from other plant genomes and therefore used in the construction of a phylogenetic tree. The phylogenetic tree revealed that AtPNP-B clustered in the same group as CjBAp12 while AtPNP-A had its own cluster group. There were also other PNP-B like molecules that clustered in the same group as expansins (α- and β-). Thus, we postulate that, like PNP-A, PNP-B also has a possible function in water and salt homeostasis. However, due to the clustering iii of AtPNP-B into the same group as CjBAp12, a possible role of PNP-B in pathogenesis-related response is also postulated.

Intrauterine crowding and placental insufficiency are main reasons for prenatal losses in swine. Two studies were conducted to examine: 1) conceptus development and in vitro steroidogenic capability of three regions of the placenta (middle, inner, polar) at d 30, 50, 70, and 90 of gestation; and 2) the effects of intrauterine position and fetal sex on conceptus development and in vitro steroidogenic activity of the placenta and endometrium at d 40, 60, 80, and 100 of gestation. All variables were examined in gilts that were uterine intact before hysterectomy (n=19) and in gilts unilaterally hysterectomized-ovariectomized (UHOX) before breeding (n=17) to induce intrauterine crowding. Placentas were combined according to the sex of the fetus associated with the placental unit (except at d 30). Placentas were sectioned into middle, inner and polar regions. Placental tissues were incubated, and release of progesterone (P₄) and estrone (E₁) was determined. Fetal survival rate was greater (P< .01, .05, .001 at d 50, 70 and 90, respectively) from intact versus UHOX gilts. Placental length and weight, fetal length and weight, and allantoic fluid volume were greater in intact compared to UHOX gilts. The polar region of the placenta released less P₄ than the other regions at d 50, 70 and 90. Uterine status (P< .005) affected P₄ release only at d 90. Sex of the fetus did not affect placental P₄ release. Region of the placenta affected E₁, release at d 30 (P< .01) and d 50 (P< .06). Uterine status did not affect E₁ release. Sex of the fetus affected (P< .001) E₁ release only at d 50. In the second study, a total of 45 gilts was used. Placentas and endometrium were combined based upon the intrauterine position of the associated fetus. Placental and endometrial tissues were incubated and release of P₄ and E₁ was determined. Uterine status (intact or UHOX) did not affect the variables measured. Intrauterine position affected fetal and placental weights (P< .02 and .01, respectively) at d 40 of gestation. No significant effect of intrauterine position was detected on placental and endometrial P₄ release. At d 100 of gestation, placentas associated with fetuses bordered in utero by fetuses of the same sex released more (P< .01) E₁ compared to placentas associated with fetuses bordered by fetuses of the opposite sex. Estrone release by the endometrium was not significantly affected by intrauterine position. Only trace amounts of testosterone and dehydroepiandrosterone sulfate were measured in the fetal fluids at all days of gestation. Intrauterine position had no effect on P₄, E₁ or androstenedione concentrations in fetal fluids. Collectively, the results indicated a) a differential release of P₄ and E₁ by the three regions of the placenta at certain days of gestation, b) no compensatory increase in placental steroidogenic activity per unit of tissue when total placental mass was reduced, and c) a limited effect of intrauterine position on placental and endometrial steroidogenesis at various days of gestation. / Ph. D.

No description available.