No description available.

Dans le contexte de raréfaction de la ressource en eau, il est nécessaire de prendre en compte le caractère de tolérance à la sécheresse dans les programmes d’amélioration variétale, en particulier pour les porte-greffes de vigne. L’objectif de cette thèse est d’analyser, à l’échelle de la plante entière, le déterminisme génétique des effets du porte-greffe sur les réponses de la tranpiration et de la croissance, au niveau de la partie aérienne, en conditions de déficit hydrique édaphique. L’étude de ces caractères complexes, soumis à une forte interaction génotype × environnement, a été conduite à partir d’une approche de génétique quantitative où ces interactions ont été intégrées par deux approches : l’utilisation des paramètres de courbes de réponses comme caractère quantitatif et la mise en oeuvre d’une analyse QTL pluriannuelle. Une population de type F1, issu du croisement Vitis vinifera Cabernet Sauvignon × Vitis riparia Gloire de Montpellier, constituée de 138 individus, a été cartographiée génétiquement avec des marqueurs microsatellites. Cette descendance a été ensuite phénotypée en position de porte-greffe, avec un greffon unique. A partir de cet outil, des QTL ont été recherchés et identifiés pour la transpiration, l’efficience d’utilisation de l’eau et la plasticité de la transpiration induite par le porte-greffe, ainsi que pour plusieurs paramètres de la croissance et de l’allocation de la biomasse au sein de la plante entière. La plasticité de la transpiration réponse à l’état hydrique du substrat est déterminée génétiquement par des régions distinctes des autres caractères descriptifs de la consommation en eau. La colocalisation de gènes candidats dans les intervalles de confiance des QTL, impliqués dans la signalisation chimique (ABA) ou hydraulique (aquaporines) permet de formuler des hypothèses sur la signalisation porte-greffe/ greffon en condition de déficit hydrique. Des régions spécifiques du génome paraissent contrôler la croissance et la vigueur conférée par le porte-greffe en conditions de déficit hydrique. Ces régions sont également indépendantes de celles contrôlant la transpiration ou l’efficience d’utilisation de l’eau. Ce résultat permet d’envisager un travail de sélection pour ces deux catégories de caractères de manière indépendante / In the water scarcity context with the global climate change, drought tolerance must be taken into account in crop genetic improvement program, particularly for grapevine rootstocks. The objective of this thesis was to analyse at the whole plant level, the genetic determinism of rootstock effect on the transpiration and growth of the scion, under edaphic water deficit conditions. The study of these complex traits, submitted to a strong genotype × environment interaction, was performed with a quantitative genetic approach. Genotype × environment interactions were integrated with two methods: first, using response curve to an environmental variable for detecting QTL, and secondly, to combine data in a multi-environment QTL analysis. The pedigree population consisted of 138 F1 individuals derived from the interspecific cross of Vitis vinifera Cabernet Sauvignon × Vitis riparia Gloire de Montpellier. This family was mapped with single sequence repeats (SSR) markers. This population was assessed as rootstock, so every genotype was grafted with the same scion. Then, QTL were detected for transpiration, water use efficiency and transpiration plasticity induced by rootstock, and for growth and biomass allocation inside the whole plant. Transpiration plasticity was represented as a function of substrate water status and was genetically determined with distinct genome regions from the other traits related to water consumption. Candidate genes involved in hormonal (ABA) or hydraulic (aquaporins) signaling between rootstock and scion, under water deficit conditions, were localized in the QTL confidence interval. Some specific genome regions were involved in growth and confered vigour genetic determinism under water deficit conditions. These regions were also different from those identified for transpiration or water use efficiency. This result allows a further selection process for these two traits groups independently.

In biochemical networks transient dynamics plays a fundamental role, since the activation of signalling pathways is determined by thresholds encountered during the transition from an initial state (e.g. an initial concentration of a certain protein) to a steady-state. These thresholds can be defined in terms of the inflection points of the stimulus-response curves associated to the activation processes in the biochemical network. In the present work, we present a rigorous discussion as to the suitability of finite-time Lyapunov exponents and metabolic control coefficients for the detection of inflection points of stimulus-response curves with sigmoidal shape.

No description available.

No description available.

Ozone, being an unstable molecule, is believed to be one of the strongest oxidant agents known to man. Rapid growth in the application of ozone — both as disinfectant and as form of alternative medicine — led to questions about the effects of uncontrolled ozone exposure and inhalation, whether intentional or unintentional, on the human body. This study specifically focussed on examining, identifying and substantiating the respiratory effect of acute exposure (10 min or less) to considerably higher ozone concentrations than reported on before (19.5 ± 0.5 ppm). Respiratory tissue of rodents (Duncan–Hartley guinea pigs of both sexes and Male Wistar rats) was subjected to ozone by utilising three distinctly diverse models of ozone introduction: (a) in vitro exposure, (b) in vivo exposure, and (c) ex vivo by employing an isolated lung perfusion model which allows for real–time, breath–by–breath data acquisition of ozone’s effect on respiratory mechanics. The effect of ozone on the isolated trachea in the presence of various drugs with well–known effects, including methacholine, isoproterenol and ascorbic acid was also examined. The results found in this study identified two direct effects on the isolated trachea due to ozone exposure: (1) a definite contraction of the isolated trachea immediately after exposure to ozone, and (2) a clearly visible and significant hyper responsiveness of the isolated trachea to irritants, e.g. methacholine. Although ozone has a negative effect on the trachea, it was concluded that ozone has no adverse effect on muscarinic acetylcholine receptors. An apparent EC50 value of ozone on the trachea was established by two different methods as (2.77 ± 0.02) x 10–3 M and (2.10 ± 0.03) x 10–3 M, respectively. Ozone furthermore displayed an attenuation of the beneficial pharmacological response of –sympathomimetic drugs (i.e. isoproterenol), while isoproterenol itself has a relaxing effect on the ozone–induced contraction of the isolated trachea. Indomethacin pre–treatment of isolated tracheal tissue significantly (77%) reduced the ozone–induced contraction of tracheal smooth muscle, suggesting that COXproducts of arachidonic acid play a prominent role in the development of pulmonary function decrements consequent to acute high–dose ozone exposure. Ascorbic acid exhibited a meaningful prophylactic effect on ozone–induced contraction of both isolated tracheal tissue and in the isolated lung perfusion model, emphasising the major role antioxidants play in both the epithelium lining fluid (ELF) of the respiratory system and in plasma throughout the body in protecting against the destructive effects of ozone. Surprisingly, pre–treatment with ascorbic acid did not prevent hyper responsiveness of isolated tracheal preparations to methacholine after a 10 min ozone (19.5 ± 0.5 ppm) exposure. In the lung perfusion model, the presence of ascorbic acid in the perfusion medium did, however, significantly reduce the magnitude and rate of decline in lung compliance after ozone exposure (46% decline with ascorbic acid versus 96% in the control study without ascorbic acid). Examination of a lung perfusion model exposed to ozone (19.5 ± 0.5 ppm O3; 5 seconds) presented a significant decline in lung compliance (95.6% within 2 min), tidal volume (70%) and maximum inspiratory flow (71.2%), with an ensuing reduction in lung elasticity and severely hampered breathing pattern. Microscopic examination after acute high–dose inhalation studies did not display any significant cellular damage, oedema or inflammation after acute high–dose ozone exposure. This suggests that significant cellular injury and inflammation is possibly not the causative factor of early breathing difficulty experienced after acute high–dose ozone inhalation, as these symptoms and particularly the result of inflammatory precursors, is believed to probably only set in at a later stage. Although the potential advantages of ozone in certain fields of medicine are not disputed, ozone, depending on its concentration and cumulative dose, can be either therapeutic or toxic. Observations in this study emphasised that even short bursts of high–dose ozone inhalation have deleterious effects on respiratory health and care should be taken not to jump to conclusions regarding ozone’s medical application without relevant scientific evidence. It must be stressed that high–dose inhalation of ozone should be avoided at all cost – especially by those with existing airway diseases. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.

Ozone, being an unstable molecule, is believed to be one of the strongest oxidant agents known to man. Rapid growth in the application of ozone — both as disinfectant and as form of alternative medicine — led to questions about the effects of uncontrolled ozone exposure and inhalation, whether intentional or unintentional, on the human body. This study specifically focussed on examining, identifying and substantiating the respiratory effect of acute exposure (10 min or less) to considerably higher ozone concentrations than reported on before (19.5 ± 0.5 ppm). Respiratory tissue of rodents (Duncan–Hartley guinea pigs of both sexes and Male Wistar rats) was subjected to ozone by utilising three distinctly diverse models of ozone introduction: (a) in vitro exposure, (b) in vivo exposure, and (c) ex vivo by employing an isolated lung perfusion model which allows for real–time, breath–by–breath data acquisition of ozone’s effect on respiratory mechanics. The effect of ozone on the isolated trachea in the presence of various drugs with well–known effects, including methacholine, isoproterenol and ascorbic acid was also examined. The results found in this study identified two direct effects on the isolated trachea due to ozone exposure: (1) a definite contraction of the isolated trachea immediately after exposure to ozone, and (2) a clearly visible and significant hyper responsiveness of the isolated trachea to irritants, e.g. methacholine. Although ozone has a negative effect on the trachea, it was concluded that ozone has no adverse effect on muscarinic acetylcholine receptors. An apparent EC50 value of ozone on the trachea was established by two different methods as (2.77 ± 0.02) x 10–3 M and (2.10 ± 0.03) x 10–3 M, respectively. Ozone furthermore displayed an attenuation of the beneficial pharmacological response of –sympathomimetic drugs (i.e. isoproterenol), while isoproterenol itself has a relaxing effect on the ozone–induced contraction of the isolated trachea. Indomethacin pre–treatment of isolated tracheal tissue significantly (77%) reduced the ozone–induced contraction of tracheal smooth muscle, suggesting that COXproducts of arachidonic acid play a prominent role in the development of pulmonary function decrements consequent to acute high–dose ozone exposure. Ascorbic acid exhibited a meaningful prophylactic effect on ozone–induced contraction of both isolated tracheal tissue and in the isolated lung perfusion model, emphasising the major role antioxidants play in both the epithelium lining fluid (ELF) of the respiratory system and in plasma throughout the body in protecting against the destructive effects of ozone. Surprisingly, pre–treatment with ascorbic acid did not prevent hyper responsiveness of isolated tracheal preparations to methacholine after a 10 min ozone (19.5 ± 0.5 ppm) exposure. In the lung perfusion model, the presence of ascorbic acid in the perfusion medium did, however, significantly reduce the magnitude and rate of decline in lung compliance after ozone exposure (46% decline with ascorbic acid versus 96% in the control study without ascorbic acid). Examination of a lung perfusion model exposed to ozone (19.5 ± 0.5 ppm O3; 5 seconds) presented a significant decline in lung compliance (95.6% within 2 min), tidal volume (70%) and maximum inspiratory flow (71.2%), with an ensuing reduction in lung elasticity and severely hampered breathing pattern. Microscopic examination after acute high–dose inhalation studies did not display any significant cellular damage, oedema or inflammation after acute high–dose ozone exposure. This suggests that significant cellular injury and inflammation is possibly not the causative factor of early breathing difficulty experienced after acute high–dose ozone inhalation, as these symptoms and particularly the result of inflammatory precursors, is believed to probably only set in at a later stage. Although the potential advantages of ozone in certain fields of medicine are not disputed, ozone, depending on its concentration and cumulative dose, can be either therapeutic or toxic. Observations in this study emphasised that even short bursts of high–dose ozone inhalation have deleterious effects on respiratory health and care should be taken not to jump to conclusions regarding ozone’s medical application without relevant scientific evidence. It must be stressed that high–dose inhalation of ozone should be avoided at all cost – especially by those with existing airway diseases. / Thesis (Ph.D. (Pharmacology))--North-West University, Potchefstroom Campus, 2011.

It is generally accepted that the Marginal Value Theorem (MVT) describes optimal foraging strategies. Some research findings, however, indicate that in natural conditions foragers not always behave according to the MVT. To address this inconsistency, in a series of computer simulations, I examined the behaviour of four types of foragers having specific foraging efficiencies and using the MVT and alternative strategies in 16 simulated landscapes in an ideal environment (no intra- and inter-species interactions). I used data on elk (Cervus elaphus) to construct the virtual forager. Contrary to the widely accepted understanding of the MVT, I found that in environments with the same average patch quality and varying average travel times between patches, patch residence times of some foragers were not affected by travel times. I propose a mechanism responsible for this observation and formulate the perfect forager theorem (PFT). I also introduce the concepts of a foraging coefficient (F) and foragers hub (), and formulate a model to describe the relationship between the perfect forager and other forager types. I identify situations where a forager aiming to choose an optimal foraging strategy and maximize its cumulative consumption should not follow the MVT. I describe these situations in a form of a mathematical model. I also demonstrate that the lack of biological realism and environmental noise are not required to explain the deviations from the MVT observed in field research, and explain the importance of scale in optimal foraging behaviour. I also demonstrate that smart foraging, which is a set of rules based on key ecological concepts: the functional response curve (FRC), satisficing, the MVT, and incorporates time limitations, should allow for fitness maximization. Thus, it should be an optimal behavior in the context of natural selection. I also demonstrate the importance of the FRC as a driver for foraging behaviors and argue that animals should focus more on increasing the slope of their FRC than on choosing a specific foraging strategy. Natural selection should, therefore, favor foragers with steep FRC. My findings introduce new concepts in behavioural ecology, have implications for animal ecology and inform wildlife management.

Cette thèse est composée de deux parties. Dans la première partie, nous proposons une théorie pour l'interaction entre l'apprentissage par renforcement et les processus de régulation homéostatique. En fait, la régulation efficace de l'homéostasie interne et la défendre contre les perturbations a besoin des stratégies comportementales complexes pour obtenir des ressources physiologiquement épuisés. À cet égard, il est essentiel que les processus cérébraux de régulation homéostatique et les processus d'apprentissage associatifs travaillent de concert. Nous proposons une théorie computationnelle normative pour régulation homéostatique par l'apprentissage associatif, où la stabilité physiologique et l'acquisition de récompense s'avèrent les mêmes objectifs, réalisables simultanément. En théorie, le cadre résout la question de longue date de la façon dont le comportement manifeste est modulée par l'état interne, et comment les animaux apprennent à agir de manière prédictive pour empêcher des défis homéostasie potentiels (répondre par anticipation). Il fournit en outre une explication normative pour choix intertemporel, aversion au risque, la concurrence entre les systèmes de motivation, et le manque de motivation pour l'injection intraveineuse de produits alimentaires. Neurobiologiquement, la théorie suggère une explication pour le rôle de l'interaction par orexine entre les circuits hypothalamiques et les noyaux dopaminergiques du mésencéphale, comme une interface entre les états internes et les comportements motivés. Dans la deuxième partie de la thèse, nous utilisons le modèle présenté dans la première partie, comme base du développement d'une théorie de la dépendance à la cocaïne. Nous soutenons que la dépendance à la cocaïne provient du système de régulation homéostatique être détourné par les effets pharmacologiques de la cocaïne sur le cerveau. Nous démontrons que le modèle réussit à expliquer une variété des aspects comportementaux et neurobiologiques de la dépendance à la cocaïne , à savoir la grandissant de l’administration de cocaine sous les conditions de long accès a cocaïne, fonction dose-réponse pour la cocaïne , rechute à l'addiction à la cocaïne provoquée par amorçage, et l'interaction entre la disponibilité du récepteur de la dopamine D2 et dépendance à la cocaïne. / This thesis is composed of two parts. In the first part, we propose a theory for interaction between reinforcement learning and homeostatic regulation processes. In fact, efficient regulation of internal homeostasis and defending it against perturbations requires complex behavioral strategies to obtain physiologically-depleted resources. In this respect, it is essential that brains homeostatic regulation and associative learning processes work in concert. We propose a normative computational theory for homeostatically-regulated reinforcement learning (HRL), where physiological stability and reward acquisition prove to be identical objectives achievable simultaneously. Theoretically, the framework resolves the long-standing question of how overt behavior is modulated by internal state, and how animals learn to predictively act to preclude prospective homeostatic challenges (anticipatory responding). It further provides a normative explanation for temporal discounting of reward, and accounts for risk-aversive behavior, competition between motivational systems, taste-induced overeating, and lack of motivation for intravenous injection of food. Neurobiologically, the theory suggests a computational explanation for the role of orexin-based interaction between the hypothalamic circuitry and the midbrain dopaminergic nuclei, as an interface between internal states and motivated behaviors. In the second part of the thesis, we use the HRL model presented in the first part, as the cornerstone for developing an Allostatic Reinforcement Learning (ARL) theory of cocaine addiction. We argue that cocaine addiction arises from the HRL system being hijacked by the pharmacological effects of cocaine on the brain. We demonstrate that the model can successfully capture a wide range of behavioral and neurobiological aspects of cocaine addiction, namely escalation of cocaine self-administration under long- but not short-access conditions, U-shaped dose-response function for cocaine, priming-induced reinstatement of cocaine seeking, and interaction between dopamine D2 receptor availability and cocaine seeking.

In biochemical networks transient dynamics plays a fundamental role, since the activation of signalling pathways is determined by thresholds encountered during the transition from an initial state (e.g. an initial concentration of a certain protein) to a steady-state. These thresholds can be defined in terms of the inflection points of the stimulus-response curves associated to the activation processes in the biochemical network. In the present work, we present a rigorous discussion as to the suitability of finite-time Lyapunov exponents and metabolic control coefficients for the detection of inflection points of stimulus-response curves with sigmoidal shape.