No description available.

The purpose of the current study was threefold: 1) to assess youths' and parents' perceptions of their competency in managing diabetes, 2) to assess family flexibility and cohesiveness, and 3) to assess the utility of self-efficacy and family factors as predictors of adherence and metabolic control. Participants included 62 youths with insulin-dependent diabetes mellitus (IDDM) and their parents. Parents' and youths' perceptions of their abilities in diabetes and related situations, family cohesion and adaptability, and perceptions of the family's ability to integrate the demands of the diabetes regimen into general family routines were assessed. Results suggested that both social learning factors and general family relations were important in the prediction of youths' adherence to the treatment regimen for diabetes and metabolic control. Moreover, family efficacy and family cohesion were related, suggesting the need for models of assessment and intervention that include both social learning and general family functioning variables. / Ph. D.

No description available.

This manuscript presents a thorough investigation and description of metabolic control dynamics in vivo and in silico using as a model de novo pyrimidine biosynthesis. Metabolic networks have been studied intensely for decades, helping develop a detailed understanding of the way cells carry out their biosynthetic and catabolic functions. Biochemical reactions have been defined, pathway structures have been proposed, networks of genetic control have been examined, and mechanisms of enzymatic activity and regulation have been elucidated. In parallel with these types of traditional biochemical analysis, there has been increasing interest in engineering cellular metabolism for commercial and medical applications. Several different mathematical approaches have been developed to model biochemical pathways by combining stoichiometric and/or kinetic information with probabilistic analysis, or deciphering the comparative logic of metabolic networks using genomic-derived data. However, most of the research performed to date has relied on theoretical analyses and non-dynamic physiological states. The studies described in this dissertation provide a unique effort toward combining mathematical analysis with dynamic transition experimental data. Most importantly these studies emphasize the significance of providing a quantitative framework for understanding metabolic control. The pathway of de novo biosynthesis of pyrimidines in Escherichia coli provides an ideal model for the study of metabolic control, as there is extensive documentation available on each gene and enzyme involved as well as on their corresponding mechanisms of regulation. Biochemical flux through the pathway was analyzed under dynamic conditions using middle-exponential growth and steady state cultures. The fluctuations of the biochemical pathway intermediates and end products transitions were quantified in response to physiological perturbation. Different growth rates allowed the comparison of rapid versus long-term equilibrium shifts in metabolic adaptation. Finally, monitoring enzymatic activity levels during metabolic transitions provided insight into the interaction of genetic and biochemical mechanisms of regulation. Thus, it was possible to construct a robust mathematical model that faithfully represented, with a remarkable predictability, the nature of the metabolic response to specific environmental perturbations. These studies constitute a significant contribution to the fields of quantitative biochemistry and metabolic control, which can be extended to other cellular processes as well as different organisms.

<p> Nitrate assimilation is the process by which nitrate is converted into ammonia, and ultimately into organic nitrogenous compounds, which are then made available to organisms which require an exogenous supply of organic nitrogen. Nitrite is an intermediate in this process and the mechanism of its conversion to ammonia, which is catalyzed by the enzyme nitrite reductase, needs clarification. </p> <p> The purpose of this investigation was to find a suitable assay system for nitrite reductase in N. crassa and to examine some aspects of the metabolic control of the enzyme. A new assay system for nitrite reductase is described and evidence suggesting that the enzyme is derepressible is presented. </p> / Thesis / Master of Science (MSc)

Background: Metabolic control declines during adolescence, increasing the risk of severe medical complications. Numerous burdensome treatments including insulin management, blood glucose monitoring, diet and exercise are necessary to prevent such complications. Adolescence is characterised by the transition from reliance on the family to independence and increased peer affiliation. It is therefore important to examine the roles of family and peer support for diabetes management tasks within a developmental context. Previous research indicates that family may have a role in supporting practical diabetes management, whilst peers may provide emotional support. Currently there is no research that compares the impact of diabetes-specific family and peer support on both metabolic control and quality of life. The present study addresses these issues. Methods: Ninety adolescents aged 13-18 with type 1 diabetes participated in this crosssectional study. Data included youth report of diabetes-specific social support (DSSQ) from peers and family, quality of life (PedsQL) and metabolic control (HbA1c). The relationships between social support, quality of life and HbA1c were examined using t-tests and correlations. Fishers Z transformations and hierarchical multiple regression were used to investigate the social support measures as potential predictors of HbA1c and quality of life. Results: Family provided significantly more support for practical diabetes management tasks than did peers. Peers provided significantly more support for exercise, but less emotional support, than did family. Better metabolic control was predicted by lower levels of peer support for insulin management, higher levels of peer support for blood glucose monitoring, increased mood and higher levels of family support for exercise. Quality of life was predicted by increased mood, higher levels of family emotional support, family support for diet, lower levels of peer support for insulin management and higher levels of peer support for exercise. Conclusion: Whilst family support remains important throughout adolescence, peer support also has an important role in the metabolic control and quality of life of adolescents with diabetes. This has implications for clinical practice, the most significant of which being the education and inclusion of peers in diabetes care.

This thesis is an investigation of the factors that impact psychological adjustment and metabolic control in children and adolescents with type 1 diabetes. Studies suggest that aspects of the family environment (stressful life events, family functioning and parent mental health) and child characteristics such as age, sex, executive functioning and hopeful thinking impact psychological adjustment and metabolic control. There is also evidence that coping processes mediate these associations. The purpose of this study was to 1) explore and identify developmental differences in coping processes in a sample of children with T1D, 2) identify the family system characteristics that are associated with child coping processes and psychological adjustment, and 3) identify the family and child characteristics that impact metabolic control. Survey data were collected through convenience sampling from an outpatient hospital clinic. Children aged 8 to 17 completed self-reports of hopeful thinking and illness-related coping style. Caregivers provided demographic information and completed questionnaires on their child’s physical health, stressful life events, mental health, family functioning, as well as the child’s initiative, emotional control, and psychological adjustment. Ratings of child metabolic control (HbA1C) were also retrieved from hospital patient records. A predictive model examining direct and indirect contributions of the family environment and coping variables toward child adjustment and metabolic control was tested. Age and sex differences in children’s coping style were identified. Family functioning and parent mental health were found to predict child psychological adjustment. Coping processes, including avoidant coping, coping efficacy and executive functioning mediated relations between family functioning and child adjustment. Results provided partial support for a mediational model of family system characteristics that influence psychological adjustment in the sample. Family functioning and parent mental health had a direct impact on children’s psychological adjustment, as well as indirect effects on adjustment through coping processes (i.e., coping style, coping efficacy, initiative and emotional control). Child age was found to moderate some paths in the proposed model. Clinical and research implications are discussed.

Magister Chirurgiae Dentium (MChD) / Chronic inflammation of the periodontium is known as periodontal disease. The inflammation can be contained only within gingival connective tissue or can progress, leading to the loss of gingival connective tissue and alveolar bone. Lately, periodontal disease is considered as a co-morbidity of diabetes mellitus (Polak, Sanui et al., 2020). Though studies that have assessed the relationship of periodontal status with the glycemic control in type 1 diabetes mellitus adolescents, such studies have not been conducted in South Africa.

Thesis (MSc (Biochemistry))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: The Hodgkin-Huxley model, created in 1952, was one of the first models in computational neuroscience and remains the best studied neuronal model to date. Although many other models have a more detailed system description than the Hodgkin-Huxley model, it nonetheless gives an accurate account of various high-level neuronal behaviours. The fields of computational neuroscience and Systems Biology have developed as separate disciplines for a long time and only fairly recently has the neurosciences started to incorporate methods from Systems Biology. Metabolic Control Analysis (MCA), a Systems Biology tool, has not been used in the neurosciences. This study aims to further bring these two fields together, by testing the feasibility of an MCA approach to analyse the Hodgkin-Huxley model. In MCA it is not the parameters of the system that are perturbed, as in the more traditional sensitivity analysis, but the system processes, allowing the formulation of summation and connectivity theorems. In order to determine if MCA can be performed on the Hodgkin-Huxley model, we identified all the discernable model processes of the neuronal system. We performed MCA and quantified the control of the model processes on various high-level time invariant system observables, e.g. the action potential (AP) peak, firing threshold, propagation speed and firing frequency. From this analysis we identified patterns in process control, e.g. the processes that would cause an increase in sodium current, would also cause the AP threshold to lower (decrease its negative value) and the AP peak, propagation speed and firing frequency to increase. Using experimental inhibitor titrations from literature we calculated the control of the sodium channel on AP characteristics and compared it with control coefficients derived from our model simulation. Additionally, we performed MCA on the model’s time-dependent state variables during an AP. This revealed an intricate linking of the system variables via the membrane potential. We developed a method to quantify the contribution of the individual feedback loops in the system. We could thus calculate the percentage contribution of the sodium, potassium and leak currents leading to the observed global change after a system perturbation. Lastly, we compared ion channel mutations to our model simulations and showed how MCA can be useful in identifying targets to counter the effect of these mutations. In this thesis we extended the framework of MCA to neuronal systems and have successfully applied the analysis framework to quantify the contribution of the system processes to the model behaviour. / AFRIKAANSE OPSOMMINMG: Die Hodgkin-Huxley-model, wat in 1952 ontwikkel is, was een van die eerste modelle in rekenaarmagtige neurowetenskap en is vandag steeds een van die bes-bestudeerde neuronmodelle. Hoewel daar vele modelle bestaan met ’n meer uitvoerige sisteembeskrywing as die Hodgkin-Huxley-model gee dié model nietemin ’n akkurate beskrywing van verskeie hoëvlak-sisteemverskynsels. Die twee velde van sisteembiologie en neurowetenskap het lank as onafhanklike dissiplines ontwikkel en slegs betreklik onlangs het die veld van neurowetenskap begin om metodes van sisteembiologie te benut. ’n Sisteembiologiemetode genaamd metaboliese kontrole-analise (MKA) is tot dusver nog nie in die neurowetenskap gebruik nie. Hierdie studie het gepoog om die twee velde nader aan mekaar te bring deurdat die toepasbaarheid van die MKA-raamwerk op die Hodgkin-Huxley-model getoets word. In MKA is dit nie die parameters van die sisteem wat geperturbeer word soos in die meer tradisionele sensitiwiteitsanalise nie, maar die sisteemprosesse. Dit laat die formulering van sommasie- en konnektiwiteitsteoremas toe. Om die toepasbaarheid van die MKA-raamwerk op die Hodgkin-Huxleymodel te toets, is al die onderskeibare modelprosesse van die neurale sisteem geïdentifiseer. Ons het MKA toegepas en die kontrole van die model-prosesse op verskeie hoëvlak, tydsonafhanklike waarneembare sisteemvlak-eienskappe, soos die aksiepotensiaal-kruin, aksiepotensiaal-drempel, voortplantingspoed en aksiepotensiaal-frekwensie, gekwantifiseer. Vanuit hierdie analise kon daar patrone in die proseskontrole geïdentifiseer word, naamlik dat die prosesse wat ’n toename in die natriumstroom veroorsaak, ook sal lei tot ’n afname in die aksiepotensiaal-drempel (die negatiewe waarde verminder) en tot ’n toename in die aksiepotensiaal-kruin, voortplantingspoed en aksiepotensiaalfrekwensie. Deur gebruik te maak van eksperimentele stremmer-titrasies vanuit die literatuur kon die kontrole van die natriumkanaal op die aksiepotensiaaleienskappe bereken en vergelyk word met die kontrole-koëffisiënte vanuit die modelsimulasie. Ons het ook MKA op die model se tydsafhanklike veranderlikes deur die verloop van die aksiepotensiaal uitgevoer. Die analise het getoon dat die sisteemveranderlikes ingewikkeld verbind is via die membraanpotensiaal. Ons het ’n metode ontwikkel om die bydrae van die individuele terugvoerlusse in die sisteem te kwantifiseer. Die persentasie-bydrae van die natrium-, kalium- en lekstrome wat tot die waarneembare globale verandering ná ’n sisteemperturbasie lei, kon dus bepaal word. Laastens het ons ioonkanaalmutasies met ons modelsimulasies vergelyk en getoon hoe MKA nuttig kan wees in die identifisering van teikens om die effek van hierdie mutasies teen te werk. In hierdie tesis het ons die raamwerk van MKA uitgebrei na neurale sisteme en die analise-raamwerk suksesvol toegepas om die bydrae van die sisteemprosesse tot die modelgedrag te kwantifiseer.

Thesis (PhD (Biochemistry))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Metabolic Control Analysis (MCA) provides a powerful quantitative framework for understanding and explaining the control and regulation within a cellular system. MCA allows the global control of a steady-state system to be quantified in terms of control coeficients, which we can express in terms of the local properties referred to as elasticity coeficients. MCA relates elasticities to control coeficients through a matrix inversion, thus allowing scientists to predict and quantify how the kinetics of the individual enzymes affect the systemic behaviour of cellular systems. Traditionally we solved this problem numerically, while we used algebraic and symbolic control analysis techniques less frequently. By using symbolic algebraic computation we present a general implementation of the symbolic matrix inversion of MCA, known as SymCA, which requires only the description of any allosteric modifier interactions and the stoichiometry of a cellular system. The algebraic expressions generated allow an in-depth analysis of the distribution of the control within a system and also of the parameters which exhibit the greatest effect on this control distribution. This also applies when the exact values for the elasticities or control coeficients are unknown. We have demonstrated that by quantifying the control patterns, referred to as `routes of regulation', inherent in all control coeficient expressions, we can gain insight into how perturbations are propagated through a cellular system and which regulatory pathways are favoured under changing conditions. / AFRIKAANSE OPSOMMING: Metaboliese Kontrole-Analise (MKA) bied 'n kragtige kwantitatiewe raamwerk om die beheer en regulering binne sellulere sisteme te verstaan en te verduidelik. 'n Sleutelaspek van MKA is dat die globale beheer van 'n sisteem met 'n bestendige toestand gekwantifiseer kan word in terme van kontrole-koefisente en dat hierdie koefisente uitgedruk kan word in terme van die sisteem se lokale eienskappe, genaamd elastisiteitskoefisente. Deur van matriksinversie gebruik te maak kan MKA die verband tussen elastisiteitskoefisente en kontrole-koefisente aflei wat mens in staat stel om te sien hoe die kinetika van die individuele ensiemreaksies die sisteemgedrag op sellulere vlak beinvloed. Die probleem word tradisioneel hoofsaaklik op numeriese wyse bereken terwyl die gebruik van algebraiese en simboliese kontrole-analise minder gereeld gebruik word. In hierdie proefskrif verskaf ons, deur van simboliese algebraiese metodes gebruik te maak, 'n generiese implementasie van die simboliese matriksinversie van MKA, genaamd SymCA, wat slegs 'n beskrywing van 'n sellulere sisteem se allosetriese interaksies en die stoichiometrie benodig. Die algebraiese uitdrukkings sodanig gegenereer stel mens in staat om 'n in-diepte analise te doen om vas te stel waar die beheer binne 'n sisteem le, asook watter parameters die grootste effek op die kontrole-verspreiding het. Dit geld selfs in die geval waar die presiese waardes van die elastisiteitskoefisente of kontrole-koefisente onbekend is. Hierdie proefskrif demonstreer hoe die kwantifisering van kontrole-patrone, ook gesien as 'roetes van regulering', wat inherent is aan kontrole-koefisent vergelykings, mens in staat stel om te sien hoe perturbasies in 'n sellulere sisteem voortplant en watter regulatoriese paaie bevoordeel word onder veranderde kondisies.