Rediscovering Kabwe

Submitted in partial fulfillment of requirements for an MA in Journalism and Media Studies in the Faculty of Humanities at the University of Witwatersrand, 2018This long-form journalism piece consists of three interwoven themes. On the one hand it is a memoir, which is by definition a factual account of one’s life and personal experience, but in reality is open to contestation and subjective interpretation. An exploration of my first six years in the mining town that was once called Broken Hill in then Northern Rhodesia, the piece also takes the form of a travelogue, recounting my observations on a subsequent trip back, 54 years later. Today the town is called Kabwe and is the capital of Central Province in Zambia. My project is an attempt to ‘fill in the gaps’ in my memory, as I was very young when I lived there, and my memories are flimsy. In addition, expatriates often live a life cut off from other communities, and I sought to find out more about the experience of these communities from the time of the town’s establishment until the present day. I have also intended my piece to be something of a sociopolitical treatise; returning to the town in February 2018, I was able to revisit places I remembered, and, building on research I had done previously, place my memories and the town as it is today in a sociopolitical context. Speaking to people in the town and drawing on accounts from family members helped me ‘rediscover’ Kabwe for myself. It helped me to round out my knowledge of the town and our life there, as well as the reasons that made my parents decide to leave on the eve of independence.XL201

Imaging Microglial/Macrophage Activation in Spinal Cords of Experimental Autoimmune Encephalomyelitis Rats by Positron Emission Tomography Using the Mitochondrial 18kDa Translocator Protein Radioligand [18F]DPA-714

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Activated microglia/macrophages play a key role in the immunopathogenesis of MS and its corresponding animal models, experimental autoimmune encephalomyelitis (EAE). Microglia activation begins at early stages of the disease and is associated with elevated expression of the 18 kDa mitochondrial translocator protein (TSPO). Thus, positron emission tomography (PET) imaging of microglial activation using TSPO-specific radioligands could be valuable for monitoring disease-associated neuroinflammatory processes. EAE was induced in rats using a fragment of myelin basic protein, yielding acute clinical disease that reflects extensive spinal cord inflammation. Enhanced TSPO expression in spinal cords of EAE rats versus those of controls was confirmed by Western blot and immunohistochemistry. Biodistribution studies in control and EAE rats were performed using the TSPO radioligand [18F]DPA-714 [N,N-diethyl-2-(2-(4-(2-fluoroethoxy)phenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)acetamide]. At 1 h after injection, almost fivefold higher levels of [18F]DPA-714 were measured in spinal cords of EAE rats versus controls. The specific binding of [18F]DPA-714 to TSPO in spinal cords was confirmed in competition studies, using unlabeled (R,S)-PK11195 [(R,S)-N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-carboxamide)] or DPA-714 in excess. MicroPET studies affirm that this differential radioactivity uptake in spinal cords of EAE versus control rats could be detected and quantified. Using [18F]DPA-714, neuroinflammation in spinal cords of EAE-induced rats could be visualized by PET, offering a sensitive technique for monitoring neuroinflammatory lesions in the CNS and particularly in the spinal cord. In addition to current MRI protocols, this approach could provide molecular images of neuroinflammation for detection, monitoring, and research in MS

A membrane - foulant interaction study

In this thesis the problem of membrane fouling has been considered from different points of view. The aim of the study is to gather information on the physical and chemical mechanisms of membrane fouling, so that selective solutions can be introduced to overcome or to diminish the problem.Anti-foaming agents (AFA) are by necessity widely used in the process industry. The severe problems during membrane filtration have been shown to be caused by AFA used in upstream process steps. AFA are amphiphilic compounds that exhibit strong adsorption on polysulfone (PSf) membranes and thus cause the first, strong, flux decline before the usual, less severe, flux decrease during permeation (chapter 1).Polypropylene glycol (PPG) as a representative of these AFA was selected as the model foulant and the DDS GR61 PSf membrane as the model membrane.The molecular mass of the solutes appears to affect the hydraulic resistance after adsorption (R a ) as do the chemical natures of solute and membrane (chapter 2). Experiments with ethylene oxide / proylene oxide (EO/PO) block copolymers indicate hydrophobicity to be of major importance. Expressing this parameter in terms of the hydrophilic - lipophilic balance (HLB) does not provide a very useful parameter, although it illustrates the qualitative tendency of R a to decrease with decreasing hydrophobicity of the polymer.Specific surface area determination (chapter 2) has illustrated that these membranes are highly porous materials. As compared to the flux through the support layer of the GR61 membrane (large pores), the flux through the PSf layer plays a dominant role due to the smaller pores. In view of this knowledge the characterization of the porosity (pore size distribution (PSD)) of the membrane was concluded to be important.The macroscopic consideration of the porosity of the PSf membrane has prompted the development of a technique for measuring PSDs (chapter 3). Herefore, dextrans were selected as calibration compounds. The retention measurements were standardized such that adsorption, configuration and concentration polarization effects were minimized. The method is applicable for pristine and fouled membranes.It has been established that the PSD within one type and even within one batch of PSf membranes shows differences. To enable the interpretation of the adsorption mechanism on PSf membranes the PSD of the fouled membrane always should be compared to that of the corresponding pristine membrane.A schematic model for the physical adsorption mechanism of PPG on PSf has been proposed. Due to adsorption small pores are blocked and do not contribute to the flux anymore. Pores intermediate in size remain unaltered after adsorption. Large pores are narrowed so that the flux through these pores after adsorption has decreased. The applicability of this model to other combinations of membranes and solutes has not been investigated.To characterize the membrane on a molecular scale, surface -sensitive spectroscopic techniques have been selected (chapter 4). Only a combination of data obtained from photoelectron spectroscopy (XPS), fast atom bombardment mass spectrometry (FAB MS) and attenuated total reflection infrared spectroscopy (ATR IR) appeared feasible in revealing the surface properties of the PSf. Similarities as well as differences between DDS GR61 and Dorr Oliver S10, both PSf membranes, were established. Criteria to distinguish between both samples have been developed.Exploiting the depth profiling properties of the three spectroscopic techniques a gradient in hydrophobicity of the membranes was established. The S02 chemical functions of the PSf are mainly oriented towards the bulk, whereas the hydrophobic CH 3 and Aryl-C-Aryl structures are more oriented towards the surface.Application of the surface -sensitive spectroscopic techniques to the PPG fouled PSf membrane (chapter 5) revealed indeed an additional layer of PPG. The question if particular chemical groups could be indicated as being responsible for the interaction in, membrane and adsorbing compound could be answered affirmatively. The entities CH 2 and CH 3 in PPG and Aryl-C(CH 3 ) 2 -Aryl in PSf form a hydrophobic interaction.In general, more insight in and knowledge on the system DDS GR61 PSf membrane and PPG as a foulant has been gathered. A PSD determination method also applicable to the fouled membrane and a molecular characterization method consisting of a combination of three spectroscopic techniques have been developed. These methods are now available for application to other membrane and foulant combinations.A general discussion (chapter 6) combines the different points of view on the PPG foulant - PSf membrane system and the obtained results. The factor hydrophobicity influences the membrane fouling. R a is for the major part determined by hydrophobicity and the interaction between PPG and PSf has been indicated as a hydrophobic one. Also the pore size alteration after PPG fouling has been established. The knowledge gathered in this study leads to a discussion about the possibilities to abolish and to avoid the fouling on membranes

Evolution within a given virulence phenotype (pathotype) is driven by changes in aggressiveness: a case study of French wheat leaf rust populations

Plant pathogens are constantly evolving and adapting to their environment, including their host. Virulence alleles emerge, and then increase, and sometimes decrease in frequency within pathogen populations in response to the fluctuating selection pressures imposed by the deployment of resistance genes. In some cases, these strong selection pressures cannot fully explain the evolution observed in pathogen populations. A previous study on the French population of Puccinia triticina, the causal agent of wheat leaf rust, showed that two major pathotypes — groups of isolates with a particular combination of virulences — predominated but then declined over the 2005-2016 period. The relative dynamics and the domination of these two pathotypes — 166 317 0 and 106 314 0 —, relative to the other pathotypes present in the population at a low frequency although compatible, i.e. virulent on several varieties deployed, could not be explained solely by the frequency of Lr genes in the landscape. Within these two pathotypes, we identified two main genotypes that emerged in succession. We assessed three components of aggressiveness — infection efficiency, latency period and sporulation capacity — for 44 isolates representative of the four P. triticina pathotype-genotype combinations. We showed, for both pathotypes, that the more recent genotypes were more aggressive than the older ones. Our findings were highly consistent for the various components of aggressiveness for pathotype 166 317 0 grown on Michigan Amber — a ‘naive’ cultivar never grown in the landscape — or on Apache — a ‘neutral’ cultivar, which does not affect the pathotype frequency in the landscape and therefore was postulated to have no or minor selection effect on the population composition. For pathotype 106 314 0, the most recent genotype had a shorter latency period on several of the cultivars most frequently grown in the landscape, but not on ‘neutral’ and ‘naive’ cultivars. We conclude that the quantitative components of aggressiveness can be significant drivers of evolution in pathogen populations. A gain in aggressiveness stopped the decline in frequency of a pathotype, and subsequently allowed an increase in frequency of this pathotype in the pathogen population, providing evidence that adaptation to a changing varietal landscape not only affects virulence but can also lead to changes in aggressiveness

L’agressivité est-elle une composante significative de l’adaptation au paysage variétal cultivé, des populations de Puccinia triticina, agent de la rouille brune du blé ?

The ability of plant pathogens — especially fungi — to cause disease is generally divided into a qualitative term, ‘virulence’, defined as the capacity of the pathogen to infect its host (compatible interaction), and ‘aggressiveness’, defined as the quantitative variation of pathogenicity on a compatible host, which usually refers to the damages caused on this host. Surveys of pathogen populations of Puccinia triticina, the causal agent of leaf rust on wheat, were performed in France during the two latest decades. This epidemiological data set revealed that qualitative resistances (Lr genes) were strongly structuring for the pathogen populations. Concretely, few years after new Lr genes are introduced in the landscape, the corresponding virulences emerge. However, the Lr genes present in the wheat cultivars might not fully explain the changes observed in the dynamics of the pathogen population, characterized by the frequency of the different ‘pathotypes’ (virulence phenotypes). The objective of my thesis was to investigate whether, under the influence of the varietal landscape, the aggressiveness can indeed act as a significant selective force for the adaptation of the P. triticina population and, if applicable, to quantify this potential impact. Chapter 1 is an introduction litterature review. Chapter 2 links the overall composition of the varietal landscape and the evolution of French pathogen populations over the decade 2006-2016. I showed that the Lr genes carried by the most frequently grown cultivars can not explain the prevalence of two pathotypes — 166 317 0 and 106 314 0 — that dominated despite the presence of other compatible pathotypes. In Chapter 3, by comparing in planta the agressiveness traits (infection efficiency, latency period and sporulation capacity) of P. triticina isolates of each dominant pathotype, I highlighted the role of aggressiveness in the changes of the composition of the pathogen population at a large spatio-temporal scale. I showed, for a given pathotype, that the frequency dynamics of a ‘pathogenotype’ — defined as the unique combination of this pathotype and a SSR genotype — was driven by its aggressiveness level. In Chapter 4, using similar experimental methods, I showed that a higher aggressiveness could explain the prevalence of certain pathogenotypes in the cultivated landscape, despite advantages provided to others pathogenotypes by their virulence phenotype.La capacité des agents phytopathogènes – notamment les champignons – à provoquer des maladies est généralement décomposée en un terme qualitatif, la ‘virulence’, définie comme la capacité à infecter la plante hôte (interaction compatible), et ‘l’agressivité’, définie comme étant la variation quantitative du pouvoir pathogène sur un hôte compatible, reflétant généralement les dommages infligés à cet hôte. Des suivis populationnels de Puccinia triticina, champignon responsable de la rouille brune du blé, ont été réalisés en France durant les deux dernières décennies. Ces données épidémiologiques ont révélé que les résistances qualitatives (gènes Lr) étaient fortement structurantes pour les populations d’agents pathogènes. Concrètement, l’introduction de nouveaux gènes Lr dans le paysage variétal précède de seulement quelques années l’émergence des virulences correspondantes. Cependant, les gènes Lr présents dans les variétés de blé n’expliquent pas entièrement les changements observés dans la dynamique de la population pathogène, caractérisée par la fréquence des ‘pathotypes’ (phénotypes de virulences). L’objectif de ma thèse était d’étudier si, sous l’influence du paysage variétal, l’agressivité pouvait être une force sélective ayant un impact sur l’adaptation des populations de P. triticina et, le cas échéant, de quantifier cet impact. Après le Chapitre 1 bibliographique introductif, le chapitre 2 fait le lien entre la composition globale du paysage cultivé et l’évolution des populations pathogènes au cours de la décénnie 2006-2016. J’ai mis en évidence que les gènes Lr présents dans les variétés françaises les plus cultivées ne peuvent à eux seuls expliquer la prévalence de deux pathotypes – 166 317 0 et 106 314 0 – ayant dominé malgré la présence d’autres pathotypes compatibles. Dans le chapitre 3, en comparant in planta les traits d’agressivité (efficacité d’infection, période de latence et capacité de sporulation) d’isolats de P. triticina appartenant à chaque pathotype dominant, j’ai mis en évidence le rôle de l’agressivité dans les changements de la composition de la population pathogène à une échelle spatio-temporelle large. J’ai notamment montré, pour un même pathotype, que la dynamique de fréquence de ‘pathogénotype’ – défini comme la combinaison unique de ce même pathotype et d’un génotype SSR – est influencée par son niveau d’agressivité. Dans le chapitre 4, en appliquant les mêmes méthodes expérimentales, j’ai montré qu’une agressivité plus élevée pouvait expliquer la prévalence de certains pathogénotypes dans le paysage variétal, malgré les avantages conférés à d’autres pathogénotypes par leur profil de virulences

Is aggressiveness a significant component of the adaptation of Puccinia triticina populations to the cultivated wheat landscape?

La capacité des agents phytopathogènes – notamment les champignons – à provoquer des maladies est généralement décomposée en un terme qualitatif, la ‘virulence’, définie comme la capacité à infecter la plante hôte (interaction compatible), et ‘l’agressivité’, définie comme étant la variation quantitative du pouvoir pathogène sur un hôte compatible, reflétant généralement les dommages infligés à cet hôte. Des suivis populationnels de Puccinia triticina, champignon responsable de la rouille brune du blé, ont été réalisés en France durant les deux dernières décennies. Ces données épidémiologiques ont révélé que les résistances qualitatives (gènes Lr) étaient fortement structurantes pour les populations d’agents pathogènes. Concrètement, l’introduction de nouveaux gènes Lr dans le paysage variétal précède de seulement quelques années l’émergence des virulences correspondantes. Cependant, les gènes Lr présents dans les variétés de blé n’expliquent pas entièrement les changements observés dans la dynamique de la population pathogène, caractérisée par la fréquence des ‘pathotypes’ (phénotypes de virulences). L’objectif de ma thèse était d’étudier si, sous l’influence du paysage variétal, l’agressivité pouvait être une force sélective ayant un impact sur l’adaptation des populations de P. triticina et, le cas échéant, de quantifier cet impact. Après le Chapitre 1 bibliographique introductif, le chapitre 2 fait le lien entre la composition globale du paysage cultivé et l’évolution des populations pathogènes au cours de la décénnie 2006-2016. J’ai mis en évidence que les gènes Lr présents dans les variétés françaises les plus cultivées ne peuvent à eux seuls expliquer la prévalence de deux pathotypes – 166 317 0 et 106 314 0 – ayant dominé malgré la présence d’autres pathotypes compatibles. Dans le chapitre 3, en comparant in planta les traits d’agressivité (efficacité d’infection, période de latence et capacité de sporulation) d’isolats de P. triticina appartenant à chaque pathotype dominant, j’ai mis en évidence le rôle de l’agressivité dans les changements de la composition de la population pathogène à une échelle spatio-temporelle large. J’ai notamment montré, pour un même pathotype, que la dynamique de fréquence de ‘pathogénotype’ – défini comme la combinaison unique de ce même pathotype et d’un génotype SSR – est influencée par son niveau d’agressivité. Dans le chapitre 4, en appliquant les mêmes méthodes expérimentales, j’ai montré qu’une agressivité plus élevée pouvait expliquer la prévalence de certains pathogénotypes dans le paysage variétal, malgré les avantages conférés à d’autres pathogénotypes par leur profil de virulences.The ability of plant pathogens — especially fungi — to cause disease is generally divided into a qualitative term, ‘virulence’, defined as the capacity of the pathogen to infect its host (compatible interaction), and ‘aggressiveness’, defined as the quantitative variation of pathogenicity on a compatible host, which usually refers to the damages caused on this host. Surveys of pathogen populations of Puccinia triticina, the causal agent of leaf rust on wheat, were performed in France during the two latest decades. This epidemiological data set revealed that qualitative resistances (Lr genes) were strongly structuring for the pathogen populations. Concretely, few years after new Lr genes are introduced in the landscape, the corresponding virulences emerge. However, the Lr genes present in the wheat cultivars might not fully explain the changes observed in the dynamics of the pathogen population, characterized by the frequency of the different ‘pathotypes’ (virulence phenotypes). The objective of my thesis was to investigate whether, under the influence of the varietal landscape, the aggressiveness can indeed act as a significant selective force for the adaptation of the P. triticina population and, if applicable, to quantify this potential impact. Chapter 1 is an introduction litterature review. Chapter 2 links the overall composition of the varietal landscape and the evolution of French pathogen populations over the decade 2006-2016. I showed that the Lr genes carried by the most frequently grown cultivars can not explain the prevalence of two pathotypes — 166 317 0 and 106 314 0 — that dominated despite the presence of other compatible pathotypes. In Chapter 3, by comparing in planta the agressiveness traits (infection efficiency, latency period and sporulation capacity) of P. triticina isolates of each dominant pathotype, I highlighted the role of aggressiveness in the changes of the composition of the pathogen population at a large spatio-temporal scale. I showed, for a given pathotype, that the frequency dynamics of a ‘pathogenotype’ — defined as the unique combination of this pathotype and a SSR genotype — was driven by its aggressiveness level. In Chapter 4, using similar experimental methods, I showed that a higher aggressiveness could explain the prevalence of certain pathogenotypes in the cultivated landscape, despite advantages provided to others pathogenotypes by their virulence phenotype

L’agressivité est-elle une composante significative de l’adaptation au paysage variétal cultivé, des populations de Puccinia triticina, agent de la rouille brune du blé ?

The ability of plant pathogens — especially fungi — to cause disease is generally divided into a qualitative term, ‘virulence’, defined as the capacity of the pathogen to infect its host (compatible interaction), and ‘aggressiveness’, defined as the quantitative variation of pathogenicity on a compatible host, which usually refers to the damages caused on this host. Surveys of pathogen populations of Puccinia triticina, the causal agent of leaf rust on wheat, were performed in France during the two latest decades. This epidemiological data set revealed that qualitative resistances (Lr genes) were strongly structuring for the pathogen populations. Concretely, few years after new Lr genes are introduced in the landscape, the corresponding virulences emerge. However, the Lr genes present in the wheat cultivars might not fully explain the changes observed in the dynamics of the pathogen population, characterized by the frequency of the different ‘pathotypes’ (virulence phenotypes). The objective of my thesis was to investigate whether, under the influence of the varietal landscape, the aggressiveness can indeed act as a significant selective force for the adaptation of the P. triticina population and, if applicable, to quantify this potential impact. Chapter 1 is an introduction litterature review. Chapter 2 links the overall composition of the varietal landscape and the evolution of French pathogen populations over the decade 2006-2016. I showed that the Lr genes carried by the most frequently grown cultivars can not explain the prevalence of two pathotypes — 166 317 0 and 106 314 0 — that dominated despite the presence of other compatible pathotypes. In Chapter 3, by comparing in planta the agressiveness traits (infection efficiency, latency period and sporulation capacity) of P. triticina isolates of each dominant pathotype, I highlighted the role of aggressiveness in the changes of the composition of the pathogen population at a large spatio-temporal scale. I showed, for a given pathotype, that the frequency dynamics of a ‘pathogenotype’ — defined as the unique combination of this pathotype and a SSR genotype — was driven by its aggressiveness level. In Chapter 4, using similar experimental methods, I showed that a higher aggressiveness could explain the prevalence of certain pathogenotypes in the cultivated landscape, despite advantages provided to others pathogenotypes by their virulence phenotype.La capacité des agents phytopathogènes – notamment les champignons – à provoquer des maladies est généralement décomposée en un terme qualitatif, la ‘virulence’, définie comme la capacité à infecter la plante hôte (interaction compatible), et ‘l’agressivité’, définie comme étant la variation quantitative du pouvoir pathogène sur un hôte compatible, reflétant généralement les dommages infligés à cet hôte. Des suivis populationnels de Puccinia triticina, champignon responsable de la rouille brune du blé, ont été réalisés en France durant les deux dernières décennies. Ces données épidémiologiques ont révélé que les résistances qualitatives (gènes Lr) étaient fortement structurantes pour les populations d’agents pathogènes. Concrètement, l’introduction de nouveaux gènes Lr dans le paysage variétal précède de seulement quelques années l’émergence des virulences correspondantes. Cependant, les gènes Lr présents dans les variétés de blé n’expliquent pas entièrement les changements observés dans la dynamique de la population pathogène, caractérisée par la fréquence des ‘pathotypes’ (phénotypes de virulences). L’objectif de ma thèse était d’étudier si, sous l’influence du paysage variétal, l’agressivité pouvait être une force sélective ayant un impact sur l’adaptation des populations de P. triticina et, le cas échéant, de quantifier cet impact. Après le Chapitre 1 bibliographique introductif, le chapitre 2 fait le lien entre la composition globale du paysage cultivé et l’évolution des populations pathogènes au cours de la décénnie 2006-2016. J’ai mis en évidence que les gènes Lr présents dans les variétés françaises les plus cultivées ne peuvent à eux seuls expliquer la prévalence de deux pathotypes – 166 317 0 et 106 314 0 – ayant dominé malgré la présence d’autres pathotypes compatibles. Dans le chapitre 3, en comparant in planta les traits d’agressivité (efficacité d’infection, période de latence et capacité de sporulation) d’isolats de P. triticina appartenant à chaque pathotype dominant, j’ai mis en évidence le rôle de l’agressivité dans les changements de la composition de la population pathogène à une échelle spatio-temporelle large. J’ai notamment montré, pour un même pathotype, que la dynamique de fréquence de ‘pathogénotype’ – défini comme la combinaison unique de ce même pathotype et d’un génotype SSR – est influencée par son niveau d’agressivité. Dans le chapitre 4, en appliquant les mêmes méthodes expérimentales, j’ai montré qu’une agressivité plus élevée pouvait expliquer la prévalence de certains pathogénotypes dans le paysage variétal, malgré les avantages conférés à d’autres pathogénotypes par leur profil de virulences