Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Objetivo: Avaliar o efeito da intervenção dietética individualizada sobre o diagnóstico nutricional e controle metabólico em diabéticos tipo 2 sedentários Casuística e Métodos: Trata-se de um ensaio clínico controlado e prospectivo com 80 adultos, de ambos dos sexos, com Diabetes Mellitus tipo 2 divididos em GI (grupo intervenção: 40 indivíduos submetidos à intervenção dietética e a utilização de hipoglicemiante) e GC (grupo controle: 40 indivíduos submetidos à medicação hipoglicemiante). Foi realizada intervenção dietética individualizada por três meses baseando-se nas recomendações da American Diabetes Association (2002). Foram analisadas as variáveis antropométricas: massa corporal total (MCT), estatura com determinação do Índice de Massa Corporal (IMC) e perímetro da cintura (PC); as variáveis bioquímicas glicemia, colesterol total, LDL-colesterol, HDL-colesterol, triglicerídeos (TG) e hemoglobina glicada (HbA1c) e as variáveis dietéticas energia, proteínas, carboidratos, lipídeos, colesterol e fibras alimentares. Para estatística inferencial foi utilizado o Anova two-way com nível de significância de 95%. Resultados: Na análise intergrupos, o GC apresentou aumento nas variáveis: MCT (&#916;%=0,78; p=0,014), IMC (&#916;%=0,76; p=0,012), PC (&#916;%=0,75; p=0,019) enquanto que o GI apresentou redução nas variáveis: MCT (&#916;%=-3,71; p<0,001), IMC (&#916;%=-3,77; p<0,001), PC (&#916;%=-3,98; p<0,001). Na comparação da média do IR intergrupos, observou-se diferença nas variáveis: energia (p<0,001), lipídeos (p=0,012), gorduras saturadas (p<0,001); colesterol dietético (p=0,006); fibras alimentares (p=0,001); glicemia (p<0,001), colesterol total (p<0,001), LDL-colesterol (p<0,001) e HbA1c (p<0,001).Conclusão: A intervenção dietética foi eficiente em melhorar o perfil antropométrico e o controle metabólico dos diabéticos tipo 2 sedentários. / Objective: To evaluate the effect of individualized dietary intervention on nutritional diagnosis and metabolic control in sedentary subjects with type 2 diabetes. Materials and methods: This controlled clinical trial, investigated 80 adults, of both sexes, with type 2 diabetes. Patients were divided into intervention group (IG: 40 individuals subjected to intervention and hypoglycemic drug) and control group (CG: 40 individuals subjected only hypoglycemic drug). Individualized dietary intervention was conducted, for three months, based on the American Diabetes Association (2002). The anthropometric variables evaluated included: total body mass (TBM) and height to calculate body mass index (BMI), and waist circumference (WC): biochemical variables assessed were: blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), and glycated hemoglobin (HbA1c): In addition, the intake of energy, protein, carbohydrate, lipid, cholesterol, and dietary fibers. For inferential statistics two-way ANOVA was used with significant level of 95%.Results: In the intergroup analysis, the CG showed increase in TBM (&#916;%=0.78; p=0.014), BMI (&#916;%=0.76; p=0.012), WC (&#916;%=0.75; p=0.019); whereas IG decreased TBM (&#916;%=-3.71; p<0.001), BMI (&#916;%=-3.77; p<0.001), WC (&#916;%=-3.98; p<0.001). In comparing the mean RI intergroups, there was difference in the variables: energy/day (p<0.001), lipids (p=0.012), saturated fats (p<0.001), cholesterol (p=0.006), dietary fibers (p=0.001); blood glucose (p<0.001), total cholesterol (p<0.001), LDL-cholesterol (p<0.001), and HbA1c (p<0.001). Conclusions: The dietary intervention was efficiently the improvement the anthropometric and metabolic control of type 2 sedentary diabetics.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Objetivo: Avaliar o efeito da intervenção dietética individualizada sobre o diagnóstico nutricional e controle metabólico em diabéticos tipo 2 sedentários Casuística e Métodos: Trata-se de um ensaio clínico controlado e prospectivo com 80 adultos, de ambos dos sexos, com Diabetes Mellitus tipo 2 divididos em GI (grupo intervenção: 40 indivíduos submetidos à intervenção dietética e a utilização de hipoglicemiante) e GC (grupo controle: 40 indivíduos submetidos à medicação hipoglicemiante). Foi realizada intervenção dietética individualizada por três meses baseando-se nas recomendações da American Diabetes Association (2002). Foram analisadas as variáveis antropométricas: massa corporal total (MCT), estatura com determinação do Índice de Massa Corporal (IMC) e perímetro da cintura (PC); as variáveis bioquímicas glicemia, colesterol total, LDL-colesterol, HDL-colesterol, triglicerídeos (TG) e hemoglobina glicada (HbA1c) e as variáveis dietéticas energia, proteínas, carboidratos, lipídeos, colesterol e fibras alimentares. Para estatística inferencial foi utilizado o Anova two-way com nível de significância de 95%. Resultados: Na análise intergrupos, o GC apresentou aumento nas variáveis: MCT (&#916;%=0,78; p=0,014), IMC (&#916;%=0,76; p=0,012), PC (&#916;%=0,75; p=0,019) enquanto que o GI apresentou redução nas variáveis: MCT (&#916;%=-3,71; p<0,001), IMC (&#916;%=-3,77; p<0,001), PC (&#916;%=-3,98; p<0,001). Na comparação da média do IR intergrupos, observou-se diferença nas variáveis: energia (p<0,001), lipídeos (p=0,012), gorduras saturadas (p<0,001); colesterol dietético (p=0,006); fibras alimentares (p=0,001); glicemia (p<0,001), colesterol total (p<0,001), LDL-colesterol (p<0,001) e HbA1c (p<0,001).Conclusão: A intervenção dietética foi eficiente em melhorar o perfil antropométrico e o controle metabólico dos diabéticos tipo 2 sedentários. / Objective: To evaluate the effect of individualized dietary intervention on nutritional diagnosis and metabolic control in sedentary subjects with type 2 diabetes. Materials and methods: This controlled clinical trial, investigated 80 adults, of both sexes, with type 2 diabetes. Patients were divided into intervention group (IG: 40 individuals subjected to intervention and hypoglycemic drug) and control group (CG: 40 individuals subjected only hypoglycemic drug). Individualized dietary intervention was conducted, for three months, based on the American Diabetes Association (2002). The anthropometric variables evaluated included: total body mass (TBM) and height to calculate body mass index (BMI), and waist circumference (WC): biochemical variables assessed were: blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides (TG), and glycated hemoglobin (HbA1c): In addition, the intake of energy, protein, carbohydrate, lipid, cholesterol, and dietary fibers. For inferential statistics two-way ANOVA was used with significant level of 95%.Results: In the intergroup analysis, the CG showed increase in TBM (&#916;%=0.78; p=0.014), BMI (&#916;%=0.76; p=0.012), WC (&#916;%=0.75; p=0.019); whereas IG decreased TBM (&#916;%=-3.71; p<0.001), BMI (&#916;%=-3.77; p<0.001), WC (&#916;%=-3.98; p<0.001). In comparing the mean RI intergroups, there was difference in the variables: energy/day (p<0.001), lipids (p=0.012), saturated fats (p<0.001), cholesterol (p=0.006), dietary fibers (p=0.001); blood glucose (p<0.001), total cholesterol (p<0.001), LDL-cholesterol (p<0.001), and HbA1c (p<0.001). Conclusions: The dietary intervention was efficiently the improvement the anthropometric and metabolic control of type 2 sedentary diabetics.

Made available in DSpace on 2016-12-06T17:07:11Z (GMT). No. of bitstreams: 1 Dissertacao Lucieli Cambri.pdf: 576726 bytes, checksum: 2f4d7c6056c88929e5f180b6d53cc248 (MD5) Previous issue date: 2007-02-15 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The purpose of the study was to analyze the cardiac autonomic modulation and the metabolic central during the rest and the physical exercise (PE) in subjects with type 2 diabetes. The group of study was composed by 22 volunteers of both sexes, sedentary, with ages between 40 and 65 years. The PE program was constituted of 3 weekly sessions, during 12 weeks, composed by walking or weight resisted exercise. They had data collected given reference to antropometric variables, biochemical variables, blood presssure and heart rate variability (HRV) in rest, capillary glycemia before and after one of the weekly sessions of PE. The referring collections of anthropometric and biochemical variables were remade after 6 and 12 weeks of PE. A walked gradual test was submitted for identification of the of HRV threshold (HRVT). The results shows that 63.6% and 89% of the evaluated ones were classified as obese as the matter of body mass index and corporal %fat (%FC) respectively. Analyzing the biochemical results, it was verified that 87.5% of the individuals had presented an increase in total cholesterol (TC) and 72.7% in triglycerides (TG). Moreover, 68.2% of the evaluated ones had presented reduced levels of HDL and glycated hemoglebin (Alc) above 7%. As well as, 87.5% had presented high LDL. During correlation analysis it was observed that TC, TG, HDL and Alc were the biochemical variables most influenced by the morphologic variables. The physiological and biochemical variables which had presented significant correlations with the HRV of rest were systolic blood pressure, heart rate (HR) of rest and fasting glycemia. The waist-to-hip ratio and the HDL had presented significant associations with the HR of rest. The average of the capillary glycemia reduced significantly. None of the morphologic variables had reduced significantly, as a chronic effect of the training, although the abdominal circunference, the sum of skinfolds and %FC had reduced. Only the HDL had presented an effect of the training. However, despite the other biochemical variables didn t present significant reductions, some subjects have passed from the inadequate condition to an adequate adjusted condition. The HRVT, based on the criteria of Lima & Kiss (1999) and Tulppo et al. (1998), was identified in all the subjects. However, based on the linear regression criteria, it was not possible to be identified in 4 subjects. There was no difference between the different criteria used to determine the HRTV. It was verified significant associations between the HRV of rest and intensity in the HRVT, using the criteria of Lima & Kiss (1999) and the HR of rest with the decreased percentage of the HR in the 5º minute of recovery. From the results obtained it is suggested that some morphological variables can influence biochemical parameters. As well as morfo-physiological and biochemical variables in the cardiac autonomic modulation. And still, the PE presents a favorable acute effect under capillary glycemia and a favorable chronic effect under morphological and biochemical variables. In addition to that, there were evidences that the HRVT might have applicability in the adequacy of training loads. / Este trabalho teve por objetivo analisar a modulação autonômica cardíaca e o controle metabólico durante o repouso e o exercício físico ÇEP) em diabéticos tipo 2. O grupo de estudo foi composto por 22 voluntários de ambos os sexOs, sedentários, com idades entre 40 e 65 anos. O programa de HP foi constituído de 3 sessões semanais, durante 12 semanas, compostas por caminhada ou exercícios resistidos com pesos. Foram coletados dados referentes as variáveis antropométricas e bioquímicas, pressão arterial e variabilidade da freqüência cardíaca (VFC) em repouso, e glicemia capilar antes e após uma das sessões semanais de EF. As coletas referentes as variáveis antropométricas e bioquímicas foram refeitas após 6 e 12 semanas de EF. Foi realizado um teste progressivo de caminhada para identificação do limiar de variabilidade da freqüência cardíaca (LiVFC). A partir dos resultados observou-se que 63,6% e 89% dos avaliados classificam-se como obesos no que se refere ao índice de massa corporal e ao %gordura corporal (%GC) respectivamente. Quanto aos resultados bioquímicos, verificou.e que 87,5% dos indivíduos apresentaram colesterol total (CT) e 72,7% triglicerídeos (TG) elevados, Além disso, 68,2% dos avaliados apresentaram níveis de HDL reduzidos e hemoglobina glicada (Alc) acima de 7%. Assim como, 87,5% apresentaram LDL elevados. Pela análise de correlação, o CT, TG, HDL e Alc foram as variáveis bioquímicas mais influenciadas pelas variáveis morfológicas. As variáveis fisiológicas e bioquímicas que apresentaram correlações significativas com a VFC de repouso foram pressão arterial sistólica, freqüência cardíaca (FC) de repouso e glicemia de jejum. A relação cintura quadril e a HDL apresentaram associações significativas com a FC de repouso. A média da glicemia capilar reduziu significativamente. Nenhuma das variáveis morfológicas reduziram significativamente, como efeito crônico do treinamento, com tendência de redução da circunferência abdominal, o somatório das dobras cutâneas e o %GC. Somente a HDL sofreu efeito do treinamento. Contudo, apesar das demais variáveis bioquímicas não terem apresentado reduções significativas, vários sujeitos passaram das condições de controle inadequado para adequado. O LiVFC, pelo critério de Lima & Kiss (1999) e de Tulppo et al. (1998), foi identificado em todos os sujeitos. Contudo, pelo critério de regressão linear não foi possível identificar em 4 sujeitos. Não houve diferença entre os critérios para determinação do LiVFC. Verificou-se associações significativas entre a VFC de repouso e intensidade no LiVFC, pelo critério de Lima & Kiss (1999) e a FC de repouso com o percentual de queda da FC no 5º minuto de recuperação. Assim, sugere-se que determinadas variáveis morfológicas estão associadas parâmetros bioquímicos e que variáveis morfo-fisiológicas e bioquímicas podem ser determinantes na modulação autonômica cardíaca. E ainda, o EF apresenta efeito agudo favorável na glicemia capilar e crônico nas variáveis morfológicas e bioquímicas. Além da obtenção de evidências de que o LiVFC pode ter aplicabilidade na adequação das cargas de treinamento.

Using data from a purposive sample of 78 parents of children with type 1 diabetes, relationships were examined between the level of metabolic control of the child with diabetes (as measured by the HbA1c percentage), parents' marital conflict, caregiver burden, and use of psychological control. Also explored were family income and the education levels of mothers and fathers. Differences between mothers and fathers were also considered. Better metabolic control (lower HbA1c) was related to lower levels of fathers' caregiver burden. Marital conflict was also associated with mothers' and fathers' caregiver burden. Finally, mothers' caregiver burden predicted mothers' use of psychological control, and fathers' caregiver burden predicted fathers' use of psychological control. Fathers' paths were stronger from marital conflict to caregiver burden and from caregiver burden to psychological control than the mothers' paths. Only fathers had a significant path from HbA1c to caregiver burden.

Thesis (PhD (Biochemistry))--University of Stellenbosch, 2009. / ENGLISH ABSTRACT: The multiplication of cells proceeds through consecutive phases of growth and division (G1, S, G2 and M phases), in a process known as the cell cycle. The transition between these phases is regulated by so-called checkpoints, which are important to ensure proper functioning of the cell cycle. For instance, mutations leading to faulty regulation of the G1/S transition point are seen as one of the main causes of cancer. Traditionally, models for biological systems that show rich dynamic behavior, such as the cell cycle, are studied using dynamical systems analysis. However, using this analysis method one cannot quantify the extent of control of an individual process in the system. To understand system properties at the process level, one needs to employ methods such as metabolic control analysis (MCA). MCA was, however, developed for steady-state systems, and is thus limited to the analysis of such systems, unless the necessary extensions would be made to the framework. The central question of this thesis focuses on quantifying the control in mathematical models of the G1/S transition by the individual cell cycle processes. Since MCA was never applied to the cell cycle, several new methods needed to be added to the framework. The most important extension made it possible to follow and quantify, during a single cell cycle, the control properties of the individual system processes. Subsequently, these newly developed methods were used to determine the control by the individual processes of an important checkpoint in mammalian cells, the restriction point. The positioning of the restriction point in the cell cycle was distributed over numerous system processes, but the following processes carried most of the control: reactions involved in the interplay between retinoblastoma protein (Rb) and E2F transcription factor, reactions responsible for the synthesis of Delayed Response Genes and Cyclin D/Cdk4 in response to growth signals, the E2F dependent Cyclin E/Cdk2 synthesis reaction, as well as the reactions involved in p27 formation. In addition it was shown that these reactions exhibited their control on the restriction point via the Cyclin E/Cdk2/p27 complex. Any perturbation of the system leading to a change in the restriction point could be explained via its e ect on the Cyclin E/Cdk2/p27 complex, showing a causal relation between restriction point positioning and the concentration of the Cyclin E/Cdk2/p27 complex. Finally, we applied the new methods, with a modular approach, to compare a number of cell cycle models for Saccharomyces cerevisiae (budding yeast) and mammalian cells with respect to the existence of a mass checkpoint. Such a checkpoint ensures that cells would have a critical mass at the G1/S transition point. Indeed, in budding yeast, a correction mechanism was observed in the G1 phase, which stabilizes the size of cells at the G1/S transition point, irrespective of changes in the specific growth rate. This in contrast to the mammalian cell cycle models in which no such mass checkpoint could be observed in the G1 phase. In this thesis it is shown that by casting specific questions on the regulation and control of cell cycle transition points in the here extended framework of MCA, it is possible to derive consensus answers for subsets of mathematical models. / AFRIKAANSE OPSOMMING: Die selsiklus bestaan uit agtereenvolgende groei- en delingsiklusse wat tot selvermeerdering lei. Die siklus word gekenmerk deur onderskeie fases (G1, S, G2 en M) wat deur sogenaamde beheerpunte gereguleer word. Hierdie beheerpunte verseker dat selvermeerdering nie ongekontroleerd kan plaasvind nie en mutasies wat lei tot foutiewe regulering van die G1/S transisiepunt word as een van die hoofoorsake van kanker beskou. Die hoofdoel van hierdie studie was om die beheer wat selsiklusprosesse op die G1/S transisie uitoefen met behulp van wiskundige modelle te kwantifiseer. Omdat biologiese sisteme soos die selsiklus ryk dinamiese gedrag vertoon, word hulle tradisioneeldeur middel van dinamiese sisteemanalise bestudeer. Die analisemetode beskik egter nie oor die vermoë om die hoeveelheid beheer wat afsonderlike sisteemprosesse op 0n sisteemeienskap uitoefen te kwantifiseer nie. Om sisteemeienskappe op prosesvlak te verstaan moet metodes soos metaboliese kontrole analise (MKA) ingespan word. MKA was egter ontwikkel om sisteme in 0n bestendige toestand te analiseer en aangesien MKA nog nooit vantevore vir selsiklus analises gebruik was nie, moes nuwe MKA tegnieke gedurende die studie ontwikkel word. Die belangrikste van die metodes maak dit moontlik om beheer (soos uitgeoefen deur die onderskeie sisteemprosesse) oor 0n enkele selsiklus na te volg en te kwantifiseer. Die nuut-ontwikkelde metodes was vervolgens gebruik om te bepaal hoe een so 0n beheerpunt in soogdierselle - die restriksiepunt - deur die onderskeie sisteemprosesse beheer word. Die studie het aangedui dat die posisie van die restriksiepunt tydens die selsiklus deur ’n verskeidenheid sisteemprosesse beheer word. Die bevinding was dat vier prosesse beduidend meer beheer op die posisie van die restriksiepunt uitoefen: Reaksies wat betrekking het op die wisselwerking tussen retinoblastoma proteïen (Rb) en E2F transkripsiefaktor; reaksies verantwoordelik vir die sintese van vertraagde responsgene en Siklien D/Cdk4 in respons tot groeiseine; die E2F afhanklike Siklien E/Cdk2 sintesereaksie; sowel as die reaksies betrokke in p27 vorming. Daar was ook aangetoon dat hierdie reaksies hul beheer op die posisie van die restriksiepunt deur die Siklien E/Cdk2/p27 kompleks uitoefen, siende enige sisteemversteuringe (wat tot veranderinge in die restriksiepuntposisie aanleiding gee) deur veranderinge in die kompleks verklaar kon word - 0n observasie wat aandui dat daar 0n kousale verhouding is tussen die posisie van die restriksiepunt en die Siklien E/Cdk2/p27 kompleks. Die nuut-ontwikkelde metodes was verder gebruik om 0n verskeidenheid selsiklusmodelle van Saccharomyces cerevisiae (bakkersgis) en soogdierselle met 0n modulêre aanpak te vergelyk om te bepaal of daar 0n massa beheerpunt in beide soogdier- en bakkersgisselle bestaan. Daar word gepostuleer dat hierdie beheerpunt verseker dat selle 0n kritiese massa by die G1/S transisiepunt bereik. Die resultate van die studie dui daarop dat bakkersgis, anders as soogdierselle, oor so 0n korreksiemeganisme beskik. Die meganisme stabiliseer die grootte van selle in die G1 fase ondanks veranderinge in die groeitempo van die selle, sodat massa homeostaties by die G1/S transisiepunt gehandhaaf word. Die studie het getoon dat moeilike vrae met betrekking tot die selsiklus beantwoord kan word deur van wiskundige modelle gebruik te maak en die probleme in die nuut-ontwikkelde metaboliese kontrole analise raamwerk te giet.

Ziel: Die beiden primären Ziele der Diabetes-Therapie sind eine möglichst optimale Einstellung des Blutzuckers sowie der Erhalt einer vergleichsweise guten Lebensqualität. Für beide Therapieziele konnte eine Vielzahl somatischer und psychischer Determinanten identifiziert werden. Relativ wenig Beachtung fand in diesem Kontext jedoch bislang die Bedeutung der therapeutischen Beziehung. Die vorliegende Dissertation untersucht, inwieweit ein unmittelbarer Zusam-menhang zwischen der Behandlungszufriedenheit der PatientInnen und den beiden anvisierten Therapiezielen besteht. Methodik: 650 PatientInnen (475 Insulin-behandelt, 171 nicht Insulin-behandelt) aus einer universitären Poliklinik, 3 Schwerpunktpraxen und 28 hausärztlichen Einrichtungen wurden befragt. Zur Erfassung der therapeutischen Beziehung wurde die Medical Interview Satisfaction Scale (MISS) verwendet, die Lebensqualität wurde mit dem WHOQOL-BREF gemessen und die Beurteilung der Blutzuckereinstellung erfolgte durch HbA1c-Werte. Die Darstellung der Ergebnisse erfolgte getrennt für mit und ohne Insulin behandelte PatientInnen. Ergebnisse: Für keines der beiden Subkollektive konnte ein Zusammenhang zwischen therapeutischer Beziehung und Blutzuckerkontrolle gefunden werden. Hingegen zeigte sich für beide Therapiegruppen eine signifikante Beziehung zu verschiedenen Aspekten der subjektiv wahrgenommenen Lebensqualität. Schlussfolgerungen: Unterschiede in der Blutzuckereinstellung waren mit der gewählten Methodik sowie dem verwendeten Konstrukt (Behandlungszufriedenheit) in dieser naturalistischen Studie nicht aufzuzeigen und ein Einbeziehen weiterer Dimensionen der therapeutischen Beziehung, insbesondere der ärztlichen Perspektive und der jeweiligen Interaktion, erscheint für weitere Untersuchungen wünschenswert. Auch wenn die signifikanten Ergebnisse in der Interaktion mit Lebensqualität z.T. als gemeinsame Kovarianz zu verschiedenen Persönlichkeitsmerkmalen interpretiert werden können, ergeben sich deutliche Hinweise, dass die therapeutische Beziehung ein Einflussfaktor der gesundheitsbezogenen Lebensqualität ist. / Objective: The primary goals in treating Diabetes are maintaining blood glucose levels as close to normal as possible and making a relatively normal quality of life achievable. A multitude of somatic and psychological determinants for both of these goals could be identified. However, relatively little consideration in this context was given to the importance of the doctor-patient-relationship. This study examines, whether a direct relationship between treatment satisfaction and the primary treatment goals exists. Methods: 650 patients (475 insulin-treated, 171 not insulin-treated) from one universitary outpatient centre, 3 specialized treatment facilities and 28 general practitioners were asked. The doctor-patient-relationship was assessed using the Medical Interview Satisfaction Scale (MISS), health-related quality of life was measured by the WHOQOL-Bref and metabolic control by HbA1c values. Results are presented separately for patients treated with and without insulin. Results: For none of the two subgroups a relationship between doctor-patient-relationship and metabolic control was detected. However, significant interactions were found for both collectives regarding different aspects of quality of life. Conclusions: Differences in metabolic control could not be shown using the chosen methods and the construct treatment satisfaction under routine conditions and further dimensions of the doctor-patient-relationship as the physician's perspective and interactional aspects are likely to be included in future studies. Even while the significant results concerning the interaction with quality of life can be interpreted as a common covariance regarding various personality dispositions there are clear indications that the doctor-patient-relationship is a determinant of health-related quality of life.

Diese Doktorarbeit behandelt die Beobachtung, daß Koregulationsmuster in Genexpressionsdaten häufig Funktionsstrukturen der Zelle widerspiegeln. Zunächst werden simulierte Genexpressionsdaten und Expressionsdaten aus Hefeexperimenten mit Hilfe von Independent Component Analysis (ICA) und verwandten Faktormodellen untersucht. In einem eher theoretischen Zugang werden anschließend Beziehungen zwischen den Expressionsmustern und der biologischen Funktion der Gene aus einem Optimalitätsprinzip hergeleitet. Lineare Faktormodelle, beispielsweise ICA, zerlegen Genexpressionsmatrizen in statistische Komponenten: die Koeffizienten bezüglich der Komponenten können als Profile von verborgenen Variablen ("Expressionsmoden") interpretiert werden, deren Werte zwischen den Proben variieren. Im Gegensatz zu Clustermethoden beschreiben solche Faktormodelle eine überlagerung biologischer Effekte und die individuellen Reaktionen der einzelnen Gene: jedes Genprofil besteht aus einer überlagerung der Expressionsmoden, die so die gemeinsamen Schwankungen vieler Gene erklären. Die linearen Komponenten werden blind, also ohne zusätzliches biologisches Wissen, aus den Daten geschätzt, und die meisten der hier betrachteten Methoden erlauben es, nahezu schwach besetzte Komponenten zu rekonstruieren. Beim Ausdünnen einer Komponente werden Gene sichtbar, die stark auf die entsprechende Mode reagieren, ganz in Analogie zu Genen, die differentielle Expression zwischen einzelnen Proben zeigen. Verschiedene Faktormodelle werden in dieser Arbeit auf simulierte und experimentelle Expressionsdaten angewendet. Bei der Simulation von Expressionsdaten wird angenommen, daß die Genexpression von einigen unbeobachteten Variablen ("biologischen Expressionsmoden") abhängt, die den Zellzustand beschreiben und deren Einfluss auf die Gene sich durch nichtlineare Funktionen, die sogenannten Genprogramme, beschreiben läßt. Besteht Hoffnung, solche Expressionsmoden durch blinde Datenanalyse wiederzufinden? Die Tests in dieser Arbeit zeigen, daß die Moden mit ICA recht zuverlässig gefunden werden, selbst wenn die Daten verrauscht oder leicht nichtlinear sind und die Anzahl der wahren und der geschätzten Komponenten nicht übereinstimmt. Regressionsmodelle werden an Profile einzelner Gene angepasst, um ihre Expression durch Expressionsmoden aus Faktormodellen oder durch die Expression einzelner Transkriptionsfaktoren zu erklären. Nichtlineare Genprogramme werden mit Hilfe von nichtlinearer ICA ermittelt: solche effektiven Genprogramme könnten zur Beschreibung von Genexpression in großen Zellmodellen Verwendung finden. ICA und verwandte Methoden werden auf Expressionsdaten aus Zellzyklusexperimenten angewendet: neben biologisch interpretierbaren Moden werden experimentelle Artefakte identifiziert, die vermutlich Hybridisierungseffekte oder eine Verunreinigung der Proben widerspiegeln. Für einzelne Komponenten wird gezeigt, daß die koregulierten Gene gemeinsame biologische Funktionen besitzen und daß die entsprechenden Enzyme bevorzugt in bestimmten Bereichen des Stoffwechselnetzes zu finden sind. Die Expressionmechanismen scheinen also - als Ergebnis der Evolution - Funktionsbeziehungen zwischen den Genen widerzuspiegeln: es wäre unter ökonomischen Gesichtspunkten vermutlich ineffizient, wenn kooperierende Gene nicht auch koreguliert würden. Um diese teleologische Vorstellung von Genexpression zu formalisieren, wird in dieser Arbeit ein mathematisches Modell zur Analyse der optimalen differentiellen Expression (ANODE) vorgeschlagen: das Modell beschreibt Regulatoren, also beispielsweise Gene oder Enzyme, und die von ihnen gesteuerten Variablen, zum Beispiel metabolische Flüsse. Das Systemverhalten wird durch eine Fitnessfunktion bewertet, die beispielsweise vom bestimmten Stoffwechselflüssen abhängt und die es zu optimieren gilt. Dieses Optimalitätsprinzip definiert eine optimale Reaktion der Regulatoren auf kleine äußeren Störungen. Zur Berechnung optimaler Regulationsmuster braucht das zu regulierende System nur teilweise bekannt zu sein: es genügt, sein mögliches Verhalten in der Nähe des optimalen Zustandes sowie die lokale Form der Fitnesslandschaft zu kennen. Die Methode wird auf zeitabhängige Störungen erweitert: um die Antwort von Stoffwechselsystemen auf kleine oszillatorische Störungen zu beschreiben, werden frequenzabhängige Kontrollkoeffizienten definiert und durch Summations- und Konnektivitätstheoreme charakterisiert. Um die vorhergesagte Beziehung zwischen Expression und Funktion zu prüfen, werden Kontrollkoeffizienten für ein großes Stoffwechselnetz simuliert, und ihre statistischen Eigenschaften werden untersucht: die Struktur der Kontrollkoeffizientenmatrix bildet die Netztopologie ab, das bedeutet, chemische Reaktionen haben gewöhnlich einen geringen Einfluss auf weit entfernte Teile des Netzes. Außerdem hängen die Kontrollkoeffizienten innerhalb eines Teilnetzes nur schwach von der Modellierung des umgebenden Netzes ab. Verschiedene plausible Annahmen über sinnvolle Expressionsmuster lassen sich formal aus dem Optimalitätsprinzip herleiten: das Hauptergebnis ist eine allgemeine Beziehung zwischen dem Verhalten und der biologischen Funktion von Regulatoren, aus der sich zum Beispiel die Koregulation von Enzymen in Komplexen oder Funktionsmodulen ergibt. Die Funktionen der Gene werden in diesem Zusammenhang durch ihre linearen Einflüsse (die sogenannten Responsekoeffizienten) auf fitnessrelevante Zellvariable beschrieben. Für Stoffwechselenzyme werden aus den Theoremen der metabolischen Kontrolltheorie Summenregeln hergeleitet, die die Expressionsmuster mit der Struktur des Stoffwechselnetzes verknüpfen. Weitere Vorhersagen betreffen eine symmetrische Kompensation von Gendeletionen und eine Beziehung zwischen Genexpression und dem Fitnessverlust aufgrund von Deletionen. Wenn die optimale Steuerung durch eine Rückkopplung zwischen Zellvariablen und den Regulatoren verwirklicht ist, dann spiegeln sich funktionale Beziehungen auch in den Rückkopplungskoeffizienten wider. Daher ist zu erwarten, daß Gene mit ähnlicher Funktion durch Eingangssignale aus denselben Signalwegen gesteuert werden. Das Modell der optimalen Steuerung sagt voraus, daß Expressionsprofile aus Linearkombinationen von Responsekoeffizientenprofilen bestehen: Tests mit experimentellen Expressionsdaten und simulierten Kontrollkoeffizienten stützen diese Hypothese, und die gemeinsamen Komponenten, die aus diesen beiden Arten von Daten geschätzt werden, liefern ein anschauliches Bild der Stochwechselvorgänge, die zur Anpassung an unterschiedliche Umgebungen notwendig sind. Alles in allem werden in dieser Arbeit empirische Beziehungen zwischen der Expression and der Funktion von Genen bestätigt. Darüber hinaus werden solche Beziehungen aus theorischen Gründen vorhergesagt. Ein Hauptziel ist es, teleologische Aussagen über Genexpression auf explizite Annahmen zurückzuführen und dadurch klarer zu formulieren, und so einen theoretischen Rahmen für die Integration von Expressionsdaten und Funktionsannotationen zu liefern. Während andere Autoren die Expression mit Funktionskategorien der Gene oder topologisch definierten Stoffwechselwegen verglichen haben, schlage ich vor, die Funktionen von Genen durch ihre Responsekoeffizienten auszudrücken. Als ein Hauptergebnis dieser Arbeit werden allgemeine Beziehungen zwischen der Funktion, der optimalen Expression und dem Programm eines Gens vorhergesagt. Soweit die Optimalitätsannahme gilt, rechtfertigt das Modell die Verwendung von Expressionsdaten zur Funktionsannotation und zur Rekonstruktion von Stoffwechselwegen und liefert außerdem eine funktionsbezogene Interpretation für die linearen Komponenten in Expressionsdaten. Die Methoden aus dieser Arbeit sind nicht auf Genexpressionsdaten beschränkt: die Faktormodelle lassen sich auch auf Protein- und Metabolitdaten anwenden, und das Optimalitätsprinzip könnte ebenfalls auf andere Steuerungsmechanismen angewendet werden, beispielsweise auf die allosterische Steuerung von Enzymen. / This thesis is concerned with the observation that coregulation patterns in gene expression data often reflect functional structures of the cell. First, simulated gene expression data and expression data from yeast experiments are studied with independent component analysis (ICA) and with related factor models. Then, in a more theoretical approach, relations between gene expression patterns and the biological function of the genes are derived from an optimality principle. Linear factor models such as ICA decompose gene expression matrices into statistical components. The coefficients with respect to the components can be interpreted as profiles of hidden variables (called "expression modes") that assume different values in the different samples. In contrast to clusterings, such factor models account for a superposition of effects and for individual responses of the different genes: each gene profile consists of a superposition of the expression modes, which thereby account for the common variation of many genes. The components are estimated blindly from the data, that is, without further biological knowledge, and most of the methods considered here can reconstruct almost sparse components. Thresholding a component reveals genes that respond strongly to the corresponding mode, in comparison to genes showing differential expression among individual samples. In this work, different factor models are applied to simulated and experimental expression data. To simulate expression data, it is assumed that gene expression depends on several unobserved variables ("biological expression modes") which characterise the cell state and that the genes respond to them according to nonlinear functions called "gene programs". Is there a chance to reconstruct such expression modes with a blind data analysis? The tests in this work show that the modes can be found with ICA even if the data are noisy or weakly nonlinear, or if the numbers of true and estimated components do not match. Regression models are fitted to the profiles of single genes to explain their expression by expression modes from factor models or by the expression of single transcription factors. Nonlinear gene programs are estimated by nonlinear ICA: such effective gene programs may be used for describing gene expression in large cell models. ICA and similar methods are applied to expression data from cell-cycle experiments: besides biologically interpretable modes, experimental artefacts, probably caused by hybridisation effects and contamination of the samples, are identified. It is shown for single components that the coregulated genes share biological functions and the corresponding enzymes are concentrated in particular regions of the metabolic network. Thus the expression machinery seems to portray - as an outcome of evolution - functional relationships between the genes: regarding the economy of resources, it would probably be inefficient if cooperating genes were not coregulated. To formalise this teleological view on gene expression, a mathematical model for the analysis of optimal differential expression (ANODE) is proposed in this work: the model describes regulators, such as genes or enzymes, and output variables, such as metabolic fluxes. The system´s behaviour is evaluated by a fitness function, which, for instance, rates some of the metabolic fluxes in the cell and which is supposed to be optimised. This optimality principle defines an optimal response of regulators to small external perturbations. For calculating the optimal regulation patterns, the system to be controlled needs to be known only partially: it suffices to predefine its possible behaviour around the optimal state and the local shape of the fitness function. The method is extended to time-dependent perturbations: to describe the response of metabolic systems to small oscillatory perturbations, frequency-dependent control coefficients are defined and characterised by summation and connectivity theorems. For testing the predicted relation between expression and function, control coefficients are simulated for a large-scale metabolic network and their statistical properties are studied: the structure of the control coefficients matrix portrays the network topology, that is, chemical reactions tend to have little control on distant parts of the network. Furthermore, control coefficients within subnetworks depend only weakly on the modelling of the surrounding network. Several plausible assumptions about appropriate expression patterns can be formally derived from the optimality principle: the main result is a general relation between the behaviour of regulators and their biological functions, which implies, for example, the coregulation of enzymes acting in complexes or functional modules. In this context, the functions of genes are quantified by their linear influences (called ``response coefficients'') on fitness-relevant cell variables. For enzymes controlling metabolism, the theorems of metabolic control theory lead to sum rules that relate the expression patterns to the structure of the metabolic network. Further predictions concern a symmetric compensation for gene deletions and a relation between gene expression and the fitness loss caused by gene deletions. If optimal regulation is realised by feedback signals between the cell variables and the regulators, then functional relations are also portrayed in the linear feedback coefficients, so genes of similar function may be expected to share inputs from the same signalling cascades. According to the model of optimal regulation, expression profiles are linear combinations of response coefficient profiles: tests with experimental expression profiles and simulated control coefficients support this hypothesis, and the common components which are estimated from both kinds of data provide a vivid picture of the metabolic adaptations that are required in different environments. To summarise, empirical relations between gene expression and function have been confirmed in this work. Furthermore, such relations have been predicted on theoretical grounds. A main aim is to clarify teleological assertions about gene expression by deriving them from explicit assumptions, and thus to provide a theoretical framework for the integration of expression data and functional annotations. While other authors have compared expression to functional gene categories or topologically defined metabolic pathways, I propose to relate it to the response coefficients. A main result of this work is that general relations are predicted between a gene's function, its optimal expression behaviour, and its regulatory program. Where the assumption of optimality is valid, the model justifies the use of expression data for functional annotation and pathway reconstruction, and it provides a function-related interpretation for the linear components behind expression data. The methods from this work are not limited to gene expression data: the factor models are applicable to protein and metabolite data as well, and the optimality principle may also apply to other regulatory mechanisms, such as the allosteric control of enzymes.

Les événements de diversification adaptative sont des éléments primordiaux de l'évolution. En effet, ils engendrent des innovations phénotypiques telles que la colonisation de nouvelles niches écologiques et au final, la spéciation. Afin d'étudier les ressorts écologiques et moléculaires de la diversification adaptative, nous utilisons la plus longue des expériences d'évolution en cours. Depuis 1988, soit plus de 60 000 générations, douze populations indépendantes issues d'un ancêtre commun d'Escherichia coli sont propagées quotidiennement dans un milieu minimum comportant une faible quantité de glucose.Un événement unique de diversification s'est produit dans une des 12 populations (Ara–2). Deux lignées de phénotypes différents sont apparues après environ 6500 générations, les S pour «Small» et les L pour «Large», chacune présentant des tailles cellulaires différentes. Les deux lignées coexistent grâce à une sélection négative dépendant de la fréquence qui favorise la lignée la plus rare et permet de supplanter sa concurrente; ainsi, aucune des deux lignées ne s'éteint. Avant l’événement de diversification, la population Ara–2 a développé un phénotype hypermutateur suite à la mutation d'un gène de réparation de l'ADN. L'objectif de cette thèse est de caractériser les mécanismes écologiques, physiologiques et moléculaires sous-tendant l'émergence et la coexistence des lignées S et L.En premier lieu, nous avons utilisé un ensemble d'expériences d'évolution in vivo et in silico afin de déterminer les moteurs écologiques et physiologiques de l'émergence de ce polymorphisme. Plusieurs mécanismes écologiques, incluant les compromis (trade-off évolutifs), la saisonnabilité et les déplacements de caractères interviennent dans l'émergence et la persistance de la diversité au long terme. Nous avons montré que la lignée L, en produisant de l'acétate, créait une nouvelle opportunité écologique exploitée par les S. De plus, au cours du temps, les S et les L s'adaptent à leur niche écologique, respectivement l'acétate et le glucose.En second lieu, nous avons cultivé les S et les L séparément pour éliminer la compétition entre les deux lignées. Dans ces conditions, il y a perte des interactions dépendantes de la fréquence entre les S et les L. Ceci démontre l'importance de la compétition dans le maintien du polymorphisme.En troisième lieu, nous avons combiné des approches génétiques, physiologiques et biochimiques pour déterminer le rôle, dans l'émergence du polymorphisme, d'une mutation spécifique aux S survenant dans le gène arcA, codant un régulateur global. Nous avons montré que l'allèle évolué de arcA augmentait la transcription de gènes du métabolisme de l'acétate dans la lignée S. Au cours de cette étude, nous avons identifié une mutation supplémentaire dans le gène acs, impliqué dans le métabolisme de l'acétate, intervenant dans l'émergence de la lignée S. Nous avons aussi démontré que ces deux mutations étaient favorables à la lignée S au début de son émergence, puis que des mutations plus tardives agissaient de façon épistatiques avec les allèles évolués de acs et de arcA. Ainsi, ces résultats démontrent que l'établissement et le maintien du polymorphisme des S et des L est un processus en plusieurs étapes nécessitant des interactions épistatiques entre plusieurs mutations.En quatrième lieu, nous avons identifié la dynamique au long terme des taux de mutations dans cette population. L'apparition et l'invasion rapide du phénotype hypermutateur est suivie d'une réversion complète mais indépendante dans chacune des lignées S et L.L'émergence d'un polymorphisme bactérien durable reflète une restructuration complexe des réseaux métaboliques et de régulation dans ces lignées qui co-existent, ce qui aboutit à l'apparition et à l'exploitation de nouvelles opportunités écologiques. La compétition et l'évolution de l'utilisation de ressources différentes sont des forces sélectives permettant le maintien du polymorphisme. / Diversification events are central issues in evolution since they generate phenotypic innovation such as colonization of novel ecological niches and, ultimately, speciation. To study the ecological and molecular drivers of adaptive diversification, we used the longest still-running evolution experiment. Twelve independent populations are propagated in a glucose limited minimal medium from a common ancestor of Escherichia coli by serial daily transfers since 1988 for more than 60,000 generations. In one of the twelve populations, called Ara–2, a unique diversification event occurred: two phenotypically-differentiated lineages, named S (Small) and L (Large) according to their cell size, emerged from a common ancestor at ~ 6500 generations. The two lineages co-exist ever since, owing to negative frequency-dependent selection whereby each lineage is favored and invades the other when rare, such that no lineage gets extinct. Moreover, and before the split between the two S and L lineages, the population Ara–2 evolved a hypermutator phenotype, owing to a defect in a DNA repair gene. The objective of this thesis is to characterize the ecological, physiological and molecular mechanisms that allowed the emergence and stable co-existence of the S and L lineages.First, we used a combination of in vivo and in silico experimental evolution to determine the ecological and physiological drivers of the emergence of the polymorphism. Several ecological mechanisms including tradeoff, seasonality and character displacement are involved in the emergence and long-term persistence of diversity. In particular, we showed that the L lineage secretes acetate which generates a new ecological opportunity that the S lineage exploited. In addition, the S and L lineages became fitter and fitter over time in their respective ecological niches, respectively acetate and glucose. Second, we propagated S and L clones separately to remove competition between the two lineages. In these conditions, frequency-dependent interactions between the S and L clones evolved separately were completely abolished, revealing the importance of competition in the maintenance of the polymorphism. Third, we combined genetic, physiological and biochemical approaches to determine the role of an S-specific mutation that was previously found in arcA, encoding a global regulator, in the emergence of the S and L polymorphism. We showed that the evolved arcA allele conferred to the S lineage the capacity to growth on acetate by increasing the transcription of target genes involved in acetate consumption. During this study, we found an additional mutation, in the acs gene involved in acetate metabolism, that was also involved in the emergence of the S lineage. We further showed that these two mutations were favorable to the S lineage early during its emergence, and that other mutations occurred later that interacted epistatically with the acs and arcA evolved alleles. Therefore, these data showed that the establishment and further maintenance of the S and L polymorphism was a multi-step process involving epistatic interactions between several mutations. Fourth, we identified the long-term dynamics of mutation rates in this divergent population. A first early rise of a hypermutator was followed by a full reversion of this mutator state twice independently in each of the two S and L lineages.The emergence of a long-term bacterial polymorphism reflects a complex restructuration of the metabolic and regulatory networks in the co-existing lineages, resulting in the generation and exploitation of a new ecological opportunity. Competition and evolution of divergent resource consumption were the selective forces driving the maintenance of the polymorphism.

Background: Specialized adult care of phenylketonuria (PKU) patients is of increasing importance. Adult outpatient clinics for inherited errors of metabolism can help to achieve this task, but experience is limited. Ten years after establishment of a coordinated transition process and specialised adult care for inherited metabolic diseases, adult PKU care was evaluated with respect to metabolic control, therapy satisfaction, life satisfaction, sociodemographic data, economical welfare as well as pregnancy outcome. Methods: All PKU patients transferred from paediatric to adult care between 2005 and 2015 were identified. A retrospective data analysis and a cross-sectional survey in a sub-cohort of 30 patients including a questionnaire for assessing quality of life (FLZm) were performed as a single-centre investigation at the metabolic department of the University Hospital Leipzig, Germany. For statistical analysis, Mann-Whitney-U-test, t-test for independent samples, ANOVA and chi square test were used as appropriate. Results: 96 PKU patients (56 females/40 males; median age 32 years, range 18–62) were included. In the last 3-year period, 81 % of the transferred patients still kept contact to the adult care centre. Metabolic control was stable over the evaluation period and dried blood phenylalanine concentrations mostly remained within the therapeutic range (median 673.0 μmol/l, range 213.0–1381.1). Sociodemographic data, economical welfare and life satisfaction data were comparable to data from the general population. However, differences could be revealed when splitting the cohort according to time of diagnosis and to management during childhood. 83 % of the PKU adults were satisfied with the transition process and current adult care. 25 completed pregnancies were supervised; three newborns, born after unplanned pregnancy, showed characteristic symptoms of maternal PKU syndrome. Conclusions: Continuous care for adult PKU patients in a specialized outpatient clinic is successful, leading to good to satisfactory metabolic control and social outcomes. Uninterrupted good metabolic treatment throughout childhood and adolescence positively influences educational, professional and economic success in later life. Further effort in specialized paediatric and adult metabolic care is needed to prevent loss of follow-up and to support the recommended life-long treatment and/or care.

In recent years, streams draining agricultural land has been suggested to exhibit high carbon dioxide (CO2) concentrations when compared to streams draining other land-types. The transport of carbon from land to ocean is mainly occurring through the chain of inland waters, and with agricultural land today representing 40% of all continental area many of these inland waters are influenced by agricultural land. The aim of this study was to improve the understanding of CO2 dynamics and its control in agricultural streams. Continuous data was collected from two catchments of different scales, near the city of Uppsala, Sweden. Both catchments are typical low-land catchments largely dominated by agricultural land. The measured CO2 concentrations were analyzed to find temporal variations and differences in dynamics between the catchments. The interplay between CO2 and parameters such as dissolved oxygen, discharge and conductivity were analyzed to determine the main drivers for CO2 dynamics. The findings show supersaturation of CO2 concentration during the full length of the measurement periods, with mean CO2 concentrations higher than what have been observed in streams draining other land-type catchments. Diel CO2 cycles were found throughout most of the measurement periods, where manual measurements were conducted to confirm these findings. The diel CO2 patterns were suggested to be heavily dependent on in-situ metabolic control while hydrological factors, such as sufficient discharge, seemed to be needed to produce a good diel CO2 signal. CO2 build-up is suggested to occur in the catchment soil and, when flushed out after rain events, result in an increasing CO2 concentration. This might be one important driver for the high levels in CO2 concentration found in the streams during summer and autumn. Analysis of the catchment areas suggest the percentage of agricultural land and the size of the catchment areas had an impact on hydrology, both for sufficient water flow to exist but also for the CO2 response after rain events. More research is encouraged, where more parameters should be investigated, such as groundwater inputs and carbonate precipitation. / Bäckar som dränerar åkermark har under de senaste åren blivit mer uppmärksammade på grund av nya studier som visat att dessa bäckar tenderar att ha högre CO2-koncentration än bäckar som dränerar andra marktyper. Idag utgör cirka 40% av all kontinentalyta åkermark, då den huvudsakliga transporten av kol från land till hav sker genom sammankopplade vattendrag är därav en förståelse av åkermarkers dränering till bäckar av stor betydelse. Syftet med studien var att förbättra förståelsen av CO2-dynamiken och dess påverkan på bäckar i jordbruksdominerade avrinningsområden. Kontinuerlig data samlades in, samt erhölls från tidigare mätningar, från två avrinningsområden med olika storlekar och markfördelningar nära Uppsala. Båda avrinningsområdena var typiska låglands- avrinningsområden som dominerades av åkermark. Data för CO2-koncentration analyserades för att hitta kort- och långsiktiga variationer i CO2-dynamiken samt undersöka hur denna dynamik skiljer sig mellan avrinningsområden med olika storlek och markfördelning. Samspelet mellan CO2 och parametrar såsom vattenlösligt syre, vattenföring och konduktivitet analyserades för att hitta drivkrafter bakom CO2-dynamiken. Resultatet visar att de undersökta bäckarna var övermättade med CO2 under hela mätperioden, samt att medelkoncentrationerna som uppmättes var högre än vad som observerats i bäckar som dränerar andra landtyper. En dygnsvariation av CO2 observerades under större delar av mätperioderna, manuella prover utfördes för att stärka denna data. Den observerade dygnscykeln av CO2-koncentrationen konstaterades korrelera med den in-situ metaboliska kontrollen medan hydrologiska faktorer, såsom ett tillräckligt högt vattenflöde, visade sig var viktigt för att en CO2-dygnscykel ska existera. De mycket höga toppar av CO2-koncentration som observerats under mätningarna tros bero på ackumulering av CO2 i avrinningsområdenas marker, vilket under nederbörd utarmas och transporteras till bäcken. Vid jämförelse av de två avrinningsområdena föreslogs den procentuella andelen åkermark och storleken av avrinningsområdet ha en stor påverkan på hydrologin, både för att ett tillräckligt vattenflöde ska existera men också för CO2-responsen vid större nederbördsmängder. Mer forskning behövs där fler parametrar börs ta i beaktning, till exempel in-situ karbonutfällning och inflöde av CO2 via grundvatten, för att få en bättre bild över åkermarkens påverkan på CO2-dynamik i bäckar.