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1
Finkel, Zoe Vanessa. "Diatoms, size and metabolic processes." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ36438.pdf.
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Ford, Yves-Yannick. "Metabolic studies of transformed roots." Thesis, University of Oxford, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260120.
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Arnold, Anne. "Modeling photosynthesis and related metabolic processes : from detailed examination to consideration of the metabolic context." Phd thesis, Universität Potsdam, 2014. http://opus.kobv.de/ubp/volltexte/2014/7227/.
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Mathematical modeling of biological systems is a powerful tool to systematically investigate the functions of biological processes and their relationship with the environment. To obtain accurate and biologically interpretable predictions, a modeling framework has to be devised whose assumptions best approximate the examined scenario and which copes with the trade-off of complexity of the underlying mathematical description: with attention to detail or high coverage. Correspondingly, the system can be examined in detail on a smaller scale or in a simplified manner on a larger scale. In this thesis, the role of photosynthesis and its related biochemical processes in the context of plant metabolism was dissected by employing modeling approaches ranging from kinetic to stoichiometric models.
The Calvin-Benson cycle, as primary pathway of carbon fixation in C3 plants, is the initial step for producing starch and sucrose, necessary for plant growth. Based on an integrative analysis for model ranking applied on the largest compendium of (kinetic) models for the Calvin-Benson cycle, those suitable for development of metabolic engineering strategies were identified.
Driven by the question why starch rather than sucrose is the predominant transitory carbon storage in higher plants, the metabolic costs for their synthesis were examined. The incorporation of the maintenance costs for the involved enzymes provided a model-based support for the preference of starch as transitory carbon storage, by only exploiting the stoichiometry of synthesis pathways.
Many photosynthetic organisms have to cope with processes which compete with carbon fixation, such as photorespiration whose impact on plant metabolism is still controversial. A systematic model-oriented review provided a detailed assessment for the role of this pathway in inhibiting the rate of carbon fixation, bridging carbon and nitrogen metabolism, shaping the C1 metabolism, and influencing redox signal transduction.
The demand of understanding photosynthesis in its metabolic context calls for the examination of the related processes of the primary carbon metabolism. To this end, the Arabidopsis core model was assembled via a bottom-up approach. This large-scale model can be used to simulate photoautotrophic biomass production, as an indicator for plant growth, under so-called optimal, carbon-limiting and nitrogen-limiting growth conditions.
Finally, the introduced model was employed to investigate the effects of the environment, in particular, nitrogen, carbon and energy sources, on the metabolic behavior. This resulted in a purely stoichiometry-based explanation for the experimental evidence for preferred simultaneous acquisition of nitrogen in both forms, as nitrate and ammonium, for optimal growth in various plant species.
The findings presented in this thesis provide new insights into plant system's behavior, further support existing opinions for which mounting experimental evidences arise, and posit novel hypotheses for further directed large-scale experiments.Mathematische Modellierung biologischer Systeme eröffnet die Möglichkeit systematisch die Funktionsweise biologischer Prozesse und ihrer Wechselwirkungen mit der Umgebung zu untersuchen. Um präzise und biologisch relevante Vorhersagen treffen zu können, muss eine Modellierungsstrategie konzipiert werden, deren Annahmen das untersuchte Szenario bestmöglichst widerspiegelt und die dem Trade-off der Komplexität der zugrunde liegenden mathematischen Beschreibung gerecht wird: Detailtreue gegenüber Größe. Dementsprechend kann das System detailliert, in kleinerem Umfang oder in vereinfachter Darstellung im größeren Maßstab untersucht werden. In dieser Arbeit wird mittels verschiedener Modellierungsansätze, wie kinetischen und stöchiometrischen Modellen, die Rolle der Photosynthese und damit zusammenhängender biochemischer Prozesse im Rahmen des Pflanzenstoffwechsels analysiert. Der Calvin-Benson-Zyklus, als primärer Stoffwechselweg der Kohlenstofffixierung in C3-Pflanzen, ist der erste Schritt der Stärke- und Saccharoseproduktion, welche maßgeblich für das Wachstum von Pflanzen sind. Basierend auf einer integrativen Analyse zur Modellklassifizierung wurden aus der größten bekannten Sammlung von (kinetischen) Modellen des Calvin-Benson-Zyklus diejenigen ermittelt, die für die Entwicklung von Metabolic-Engineering-Strategien geeignet sind. Angeregt von der Fragestellung warum Kohlenstoff transitorisch vorwiegend in Form von Stärke anstatt Saccharose gespeichert wird, wurden die metabolischen Kosten beider Syntheseprozesse genauer betrachtet. Die Einbeziehung der Bereitstellungskosten der beteiligten Enzyme stützt die Tatsache, dass bevorzugt Stärke als temporärer Kohlenstoffspeicher dient. Die entprechende Untersuchung erfolgte einzig auf Grundlage der Stöchiometrie der Synthesewege. In vielen photosynthetisch-aktiven Organismen findet zudem Photorespiration statt, die der Kohlenstofffixierung entgegenwirkt. Die genaue Bedeutung der Photorespiration für den Pflanzenmetabolismus ist noch umstritten. Eine detaillierte Einschätzung der Rolle dieses Stoffwechselweges bezüglich der Inhibierung der Kohlenstofffixierungsrate, der Verknüpfung von Kohlenstoff- und Stickstoffmetabolismus, der Ausprägung des C1-Stoffwechsels sowie die Einflussnahme auf die Signaltransduktion wurde in einer modell-basierten, kritischen Analyse vorgenommen. Um die Photosynthese in ihrem metabolischen Kontext verstehen zu können, ist die Betrachtung der angrenzenden Prozesse des primären Kohlenstoffmetabolismus unverzichtbar. Hierzu wurde in einem Bottom-up Ansatz das Arabidopsis core Modell entworfen, mittels dessen die Biomasseproduktion, als Indikator für Pflanzenwachtum, unter photoautotrophen Bedingungen simuliert werden kann. Neben sogenannten optimalen Wachstumsbedingungen kann dieses großangelegte Modell auch kohlenstoff- und stickstofflimitierende Umweltbedingungen simulieren. Abschließend wurde das vorgestellte Modell zur Untersuchung von Umwelteinflüssen auf das Stoffwechselverhalten herangezogen, im speziellen verschiedene Stickstoff-, Kohlenstoff- und Energiequellen. Diese auschließlich auf der Stöchiometrie basierende Analyse bietet eine Erklärung für die bevorzugte, gleichzeitige Aufnahme von Nitrat und Ammonium, wie sie in verschiedenen Spezies für optimales Wachstum experimentell beobachtet wurde. Die Resultate dieser Arbeit liefern neue Einsichten in das Verhalten von pflanzlichen Systemen, stützen existierende Ansichten, für die zunehmend experimentelle Hinweise vorhanden sind, und postulieren neue Hypothesen für weiterführende großangelegte Experimente.
4
Acerenza, Luis. "Studies on the control of time-dependent metabolic processes." Thesis, University of Edinburgh, 1991. http://hdl.handle.net/1842/14242.
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Sensitivity analysis studies how changes in the parameters affect the system's variables. Its application to metabolic systems (Metabolic Control Analysis, MCA) was traditionally developed under certain assumptions:i) the steady state is stable (the effect on the steady state values only is studied).ii) each reaction is catalyzed by one enzyme, the rates being proportional to the corresponding enzyme concentration.iii) the parameters are changed by a small (strictly speaking infinitesimal) amount. In the present work MCA is extended to deal with the instantaneous values of time-dependent metabolite concentrations and fluxes. Their summation and connectivity relationships are derived. In some cases it is more convenient to characterize the time courses by time-invariant variables (such as period and amplitude in oscillating systems). Summation relationships for time-invariant variables are also derived. Stability analysis shows that a linear chain of four enzyme-catalized reactions, where the third metabolite is a negative effector of the first enzyme constitutes a 'minimal' oscillator. The model is used to gain insight into the control of oscillations. The control exerted by enzyme concentrations and other parameters that are not proportional to the rate is appropriately described by parameter-unspecified coefficients (Cv). A proof of the theorems of steady-state MCA in terms of Cv is given. By a similar procedure an attempt is made to derive the theorems in terms of Cv for time-dependent systems, which is only successful for the particular case of constant π-matrix. The effect that a simultaneous change in all the enzyme concentrations by the same factor α (Coordinate-Control Operation. CCO) has on the variables of time-dependent metabolic systems is investigated. This factor α can have any arbitrary large value. The metabolic variables are classified according to the relationships they fulfil when the CCO is applied. A method is given to test these relationships in experimental systems and quantify deviations from the predicted behaviour.
5
Li, Yanjun. "COMPUTATIONAL MODELING OF IN VIVO METABOLIC PROCESSES IN SKELETAL MUSCLE." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1283473428.
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Cairns, Andrew G. "Design and synthesis of small molecule probes for metabolic processes." Thesis, University of Glasgow, 2013. http://theses.gla.ac.uk/4897/.
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Synthesis of a photoactivated uncoupler I was completed and subsequently used by collaborators to demonstrate mitochondria uptake. The synthesis of a ratiometric, targetable calcium sensor was completed up to intermediate II (9 steps), alongside a thiohydantoin heterocycle III synthesised in 5 steps. A co-worker has subsequently completed the probe synthesis based on this route, with the resulting probe showing good binding and optical responses in testing. Numerous routes to 5,6-disubstituted phenanthridinium salts were investigated towards the synthesis of a mitochondrially targeted superoxide probe and hydroxylated standards. In the course of this work a novel cyclisation was developed based on intramolecular SNAr giving access to 9-benzyloxyphenanthridinium salt V. Rapid and high-yielding access to 5,6-disubstituted phenanthridinium salts IX was then achieved through forming benzophenones VIII via Suzuki coupling and converting these to imines with the alkylamine. The nitrogen atom of the imine then undergoes cyclisation onto the aryl fluoride in an intramolecular SNAr upon heating. This transformation was shown to have good steric and electronic tolerance in the synthesis of 13 phenanthridinium analogues with 6 structural diversification points. Subsequent DFT calculations by a colleague showed this reaction proceeds in a concerted fashion and as such represents a considerable mechanistic novelty. Efforts towards a new probe for mitochondrial superoxide led to the synthesis of 3-tertbutyl-dihydrophenanthridine X, which does not intercalate into DNA upon oxidation. This concept was refined and lead to the development of neopentyl ethidium XI and the targeted analogue MitoBNH XII and its deuterated analogue XIII.
7
Soeprijanto. "Study of phosphorous released and removal under anaerobic and aerobic conditions." Thesis, University of Strathclyde, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.249057.
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Barr, Sarah Marie. "Origins and consequences of altered metabolic processes in obese pregnant women." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8827.
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Maternal obesity is an increasing concern in the obstetric population. It confers increased morbidity and mortality to the mother and offspring during pregnancy and delivery as well as potential long-term increase in risk of ill health to the offspring. There are currently few effective interventions and no pharmacological therapies. Potential mechanisms to account for ill health in obese non-pregnant individuals include excess inflammation, both systemically and within specific tissues such as adipose, as well as alterations in metabolic regulation including hyperglycaemia, reduced sensitivity to insulin and altered adipokine expression. In healthy pregnancy, there are significant adaptations to maternal metabolism, including the development of profound systemic insulin resistance. We hypothesize that there exists an interaction between the metabolic adaptations of pregnancy and those occurring in obesity which could provide a physiologically plausible mechanism which could contribute to the pathogenesis of adverse outcomes associated with obese pregnancies. In this thesis, we sought to understand and define the metabolic adaptations to pregnancy in severely obese women. Anthropometric characteristics are described in a longitudinal case-control study of apparently healthy obese (BMI > 40kg/m2) pregnant women. Systemic adipokine and pro- inflammatory cytokine profiles were measuring using ELISA. Indices of insulin sensitivity were assessed at three time points in pregnancy. In a cohort study of healthy pregnant women in the third trimester, transcript levels of adipokines and inflammatory cytokines in paired subcutaneous and omental adipose tissue biopsies were quantified and correlated these transcript levels with booking body mass index (BMI). Obese pregnant women gained less weight in pregnancy compared to lean women, but had significantly elevated fasting third trimester glucose, as well as elevated blood pressure and fasting insulin resistance throughout pregnancy. Fasting leptin was elevated throughout pregnancy in obese compared with lean pregnancy women; however, in the third trimester there was no correlation between adipose tissue leptin mRNA levels and BMI. Transcript levels of IL-6 were positively correlated with BMI in subcutaneous but not omental adipose tissue; no other positive correlations with BMI were shown. Hyperinsulinaemic euglycaemic clamps with concomitant use of stable isotope tracers were carried out in a case-control study of healthy obese pregnant women to characterise in detail whole body insulin sensitivity, endogenous glucose production and rate of lipolysis. In contrast to the original hypothesis, by the third trimester, there were few differences between lean and obese pregnant women in whole body glucose disposal (WGD) and endogenous glucose production. Compared with non-pregnant women, lean pregnant women demonstrated approximately 60% decrement in WGD; in contrast, obese non-pregnant women were already significantly insulin resistant but did not develop further insulin resistance in response to pregnancy. 3-Tesla (3T) Magnetic Resonance Imaging (MRI) and 1H-Magnetic Resonance Spectroscopy (1H-MRS)was used to assess abdominal fat distribution, hepatic and skeletal muscle lipid content in a case-control study of healthy pregnant women in the third trimester. As expected, obese pregnant women have greater adipose accumulation in both subcutaneous and intra-abdominal adipose depots and greater lipid accumulation in skeletal muscle. However, hepatic lipid content was low in both groups and there were no significant differences between lean and obese pregnant women. This was not expected as both groups are profoundly insulin resistant at this at this gestation, and in non-pregnant individuals, insulin resistance at this level would be expected to drive hepatic lipid accumulation, and may point to a pregnancyspecific hepato-protective mechanism. In conclusion, in this thesis, it has been shown that while obese women are insulin resistant with an adverse metabolic profile, that there does not appear to be the expected worsening of this profile in response to pregnancy and that by the end of pregnancy, lean women have a similar phenotype. Instead, while lean women are exposed to this environment only towards the end of pregnancy, obese women and their offspring are exposed throughout gestation, including key periods of fetal development in early pregnancy. This prolonged exposure may account for the excess pathologies in such pregnancies, potentially by exhausting what physiological reserve such women have pre-pregnancy. Potential therapies must therefore be optimally timed to improve the metabolic profile of obese women in early pregnancy, without hindering the required adaptations of the third trimester.
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McWhorter, Todd Jason. "The integration of digestive, metabolic and osmoregulatory processes in nectar-eating birds." Diss., The University of Arizona, 2002. http://hdl.handle.net/10150/280198.
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Nectarivorous birds are represented by three major radiations: hummingbirds, honeyeaters, and sunbirds. These lineages share a number of convergent features in ecology, morphology, physiology, and behavior, and have served as important models in the study of foraging strategies and energetics. Because their diet is rich in water and sugar but poor in nitrogen and electrolytes, nectarivores provide a striking opportunity for evaluation of physiological constraints. My research emphasizes a novel aspect of the water-energy interaction: water overingestion in nectar-eating birds. The dual purpose of my dissertation research was to investigate the physiological mechanisms that allow nectar-eating birds to cope with exceedingly high ingestion of water and to elucidate the consequences of ingesting and processing large quantities of water for energy intake and for the maintenance of balance of important metabolites such as glucose. In nectar-eating birds, water overabundance in food has the potential effect of constraining energy procurement by overwhelming osmoregulatory processes and limiting digestive function. My research has allowed the development of an integrated quantitative description of gut and kidney function under the broad range of water loads and hydration conditions that birds can experience in the wild. Understanding limits to water processing will provide general insights into how animals are designed, on how aspects of design constrain their ecological performance, and into how aspects of design in one physiological system can impose limits on other systems. The osmoregulatory processes of nectar-eating birds highlight the relevance of understanding the impact that events taking place in the gut can have for feeding behavior, and renal and metabolic function. Adopting a broadly comparative approach to understanding the interaction between feeding behavior, digestion, and osmoregulation is pertinent because is unclear whether the many extreme physiological characteristics of hummingbirds that have traditionally been assumed to be associated with a nectar-feeding habit are shared by other nectar-eating birds. In my dissertation research I have begun to examine the similarities, and have found some important differences, in the responses of two major radiations of nectar-eating birds to their sugary and watery diets.
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Song, Yang. "Electrostatically controlled enzymatic reaction, metabolic processes and microbial generation of electric power." Cleveland State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=csu1398685271.
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Arnold, Anne [Verfasser], and Joachim [Akademischer Betreuer] Selbig. "Modeling photosynthesis and related metabolic processes : from detailed examination to consideration of the metabolic context / Anne Arnold. Betreuer: Joachim Selbig." Potsdam : Universitätsbibliothek der Universität Potsdam, 2014. http://d-nb.info/1063166837/34.
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Louw, Roan. "Perturbation of critical metabolic processes associated with 3-hydroxynorvaline induced teratogenesis / R. Louw." Thesis, North-West University, 2004. http://hdl.handle.net/10394/698.
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Neural tube defects (NTD) are a group of folate-responsive congenital defects that
occur relatively frequently in humans. NTD display a multi-factorial aetiology,
resulting from a complex interplay of genetic and environmental factors (i.e. dietary
folate and/or vitamin B12 deficiency, teratogenic xenobiotics, etc.). β-Hydroxynorvaline
(HNV) is a proven toxic, non-protein amino acid (xenobiotic agent),
structurally related to L-threonine and L-serine and able to substitute L-threonine
in the primary structure of proteins. The main objectives of this study were to
investigate the teratogenic potential of HNV in the chicken embryo and Hanover
NMRl mouse embryo models and to elucidate some of the molecular mechanisms
involved in the aetiology of NTD.
HNV was dosed to chicken embryos (in ovo), 24 h post incubation (p.i.) at 37.8 °C
± 0.5 °C. Controls received a sterile saline solution. Chicken embryos were
removed 12 days p.i., weighed, fixed in Allen's solution and investigated
stereo-microscopically to assess the incidence and nature of dysmorphogenic
events (i.e. NTD). Body, toe and beak lengths of the chicken embryos were
measured. Chicken embryo fibroblasts were cultured and used to measure the
effect of HNV on the biosynthesis of DNA in fibroblasts.
Pregnant Hannover NMRl female mice were dosed with HNV or a saline solution
(per os) on days 7-9 post coitus (p.c.). Following the last dose of HNV on day 9,
the pregnant mice were placed in metabolic cages for 24 h to collect urine
samples. Urinary organic acids (GC-MS), acylcarnitines and amino acids (ESI-MSMS)
were quantitatively and qualitatively determined to assess the catabolic
breakdown of H NV and its effects on vital metabolic processes, such as amino
acid catabolism and the P-oxidation of fatty acids.
Control and HNV exposed mouse embryos were removed on days 10 or 18 post
coitus (p.c.). Embryos, removed from each individual mother on day 10 were
pooled and either immediately used to assess the catalytic activity of the glycine
cleavage system (GCS), or stored at -75 °C until the catalytic activities of cytosolic
(cSHMT), mitochondria1 serine hydroxymethyltransferase (mSHMT) and citrate
synthase (CS) could be assayed. Mouse embryos removed on day 18 p.c.,
weighed and stereo-microscopically investigated to assess the incidence and
nature of dysmorphogenic events. Bio-indicators of the effect of HNV on the flow
of one-carbon units through the folate and remethylation cycles (i.e. [3H]-thyrnidine
incorporation, DNA methylation and synthesis, polyamine synthesis, carnitine
synthesis, etc.) were determined in the liver tissues of pregnant females and in
pooled batches of whole embryos.
HNV proved to be embryotoxic and displayed the capacity to induce a variety of
congenital defects, including NTD, in both the chicken and mouse embryo models.
The incidence of NTD in both models proved to be dose-dependent. Selected
stereoisomers of HNV were rapidly catabolised and the main HNV derived
metabolite in the urines of HNV treated pregnant mice, was identified as 2,3-
dihydroxypentanoic acid (DHPA; GC-MS). The structure of DHPA was confirmed
by chemical synthesis and subsequent GC-MS, NMR (13c-NMR, 1H-NMR,
HETCOR and COSY) spectroscopy and IR spectrometry.
HNV altered the flow of one-carbon units through the folate and remethylation
cycles, causing a decrease in DNA synthesis, DNA methylation, polyarnine
biosynthesis, carnitine and trimethyllysine synthesis. Free carnitine stores in HNV
treated pregnant mice appeared to be depleted, probably due to a combined effect
of the detoxification of vast amounts of accumulated metabolites, generated as a
result of HNV toxicosis and decreased carnitine biosynthesis. HNV also appeared
to have altered serinelglycine interconversion, due to an inhibition of cSHMT and
to a lesser degree the inhibition of GCS. Organic acid profiles of urine samples,
collected from HNV treated pregnant mice, suggested that HNV had induced a
general ketothiolase defect in pregnant females by inhibiting the P-oxidation of
fatty acids, isoleucine catabolism and ketone body utilisation.
HNV affected the hornocysteine to cysteine transulffuration by acting as a
substrate for CBS, culminating in the biosynthesis of Sethylcysteine (GC-MS).
The presence of 3-ethylcysteine in the urines of HNV treated pregnant mice was
confirmed by GC-MS. following its in vitro synthesis, employing a reaction system
containing mouse liver hornogenate, homocysteine, HNV and pyridoxal-5-
phosphate.
In conclusion, HNV can apparently cause multiple metabolic perturbations in
pregnant mice and their developing embryos. One-carbon flux, energy metabolism
and a number of other vital biochemical processes can be adversely affected,
resulting in a disturbance of normal embryonic development (i.e. proper closure of
the neural tube) and subsequent dysmorphogenesis in developing embryos.Thesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.
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Jing, Chenzhi. "Characterisation of the effect and functional significance of Fcγ receptor crosslinking on metabolic processes in macrophages." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/280316.
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The metabolic state of an immune cell directly influences its ability to function and differentiate, ultimately affecting immunity, inflammation and tolerance. Different immune cell subsets have differing metabolic requirements. Macrophages, as the frontline, tissue-resident cells of the innate immune system, undergo profound metabolic reprogramming in response to environmental stimuli. To date, there has been little consideration how macrophage metabolism might be affected by humoral immunity. IgG antibodies are the soluble effector molecules of the adaptive humoral immune system. Fcγ receptors (FcγRs) mediate the cellular functions of IgG antibodies and are expressed on most immune cells including macrophages. FcγR cross-linking induced by IgG immune complexes (ICs) is important for defence against some infections but can also play a pathogenic role in autoimmunity. Here, I studied the metabolic reprogramming induced in macrophages by IgG IC ligation of FcγRs. I first investigated how FcγRs cross-linking might impact glucose metabolism. We show that macrophages undergo a switch to glycolysis in response to IgG IC stimulation. FcγR-associated glycolysis was dependent on the mammalian target of rapamycin (mTOR) and hypoxia-inducible factor (HIF)1α. Moreover, this glycolytic switch was required to generate a number of pro-inflammatory mediators and cytokines. Inhibition of glycolysis, or genetic depletion of HIF1α in macrophages resulted in the attenuation of IL1β and other inflammatory mediators produced in response to IgG IC in vitro. To determine the relevance of these observations to responses to IgG IC in vivo and, in particular, to IC-associated tissue inflammation in autoimmune diseases such as system lupus erythematosus (SLE), I developed three models to interrogate tissue macrophages. Following administration of IC to peritoneal macrophages, I observed IL1β-associated neutrophil recruitment that was abrogated by inhibiting glycolysis, or in the presence of HIF-1a deficiency. Similarly, following administration of intravenous IC, or nephrotoxic serum, kidney macrophage activation was abrogated by glycolysis inhibition or by myeloid HIF-1a deficiency. Together my data reveal the cellular molecular mechanisms required for FcγR-mediated metabolic reprogramming in macrophages and define a novel therapeutic strategy in autoantibody-induced inflammation. In the final part of the thesis I identified additional metabolic pathways that were altered by FcγR ligation, including cholesterol biosynthesis and fatty acid biosynthesis. This has important implications for protective immune responses and autoimmune susceptibility, since a number of intermediates in these pathways can directly regulate and contribute to immune responses. In summary, I have demonstrated the metabolic alterations triggered by FcγR ligation, reveal the cellular molecular mechanisms required for FcγR-mediated cellular respiration reprogramming in macrophages and define a potential therapeutic target in autoimmunity.
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Waterworth, James Stephen. "Anaerobic biodegradation of Peptidoglycan and Chitin by freshwater and marine sediment bacteria." Thesis, Queen Mary, University of London, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266849.
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Maibaum, Elaine Catherine. "Spectro-electro-array spectroscopy and the in-vitro modelling of metabolic processes and reactive intermediates." Thesis, Imperial College London, 2004. http://hdl.handle.net/10044/1/8599.
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Nelson, Jasmine N. Fadel Paul J. "Metabolic and autonomic nervous system effects of bariatric surgery." Diss., Columbia, Mo. : University of Missouri-Columbia, 2009. http://hdl.handle.net/10355/6658.
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The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 5, 2010). Thesis advisor: Paul J. Fadel. "December 2009" Includes bibliographical references.
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Yacob, Shahrakbah, and n/a. "Metal-reducing microorganisms in petroleum reservoirs." University of Canberra. Resource & Environmental Science, 2000. http://erl.canberra.edu.au./public/adt-AUC20061112.102729.
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Metal-reducing microorganisms reduce a variety of metals in metabolic processes
coupled to the oxidation of organic compounds. These bacteria play an important role
in the biogeochemical cycling of metals and organic matter in anaerobic aquatic and
sediment ecosystems. It has been proposed recently that metal-reducing
microorganisms also are active in deep subsurface environments such as petroleum
reservoirs. Only two metal-reducing bacteria have been isolated from petroleum
reservoir fluids, Shewanella putrefaciens and Deferribacter thermophilus. This project
studied the occurrence and distribution of metal-reducing microorganisms in petroleum
reservoirs. The research focused on the isolation, characterisation and identification of
anaerobic bacteria from petroleum reservoirs that were capable of reducing metals and
the potential roles of these isolates in the microbial ecology and biogeochemical cycling
of petroleum reservoirs.
Petroleum reservoirs were selected for this study on the basis of physio-chemical
conditions such as temperature, salinity, pH and the presence of organic and inorganic
compounds, that were likely to provide a suitable environment for anaerobic bacteria
capable of reducing metals. Factors such as the stratigraphic features of the
sedimentary basin, age of reservoir and past oil field practices also were considered in
choosing the reservoir for study. Seven petroleum reservoirs in the USA and
Azerbaijan were chosen for extensive investigations. The physico-chemical conditions
in these reservoirs varied substantially.
A systematic study of the production water from these petroleum reservoirs revealed a
consistent presence of iron- and manganese-reducing microorganisms. It was found
that salinity and temperature play a significant and defining role in the occurrence and
distribution of these metal-reducing microorganisms. Biotic metal reduction was
detected from production waters from all but one of the oil wells sampled. It was
significant that the water from this well (Neftcala #1074) was the most saline (78 g/l
NaCI). Metal-reducing activity was detected at temperatures up to 70°C.
Two pure cultures, strains RED1 for Redwash petroleum reservoir (USA) and NEF1
from the Neftcala petroleum reservoir (Azerbaijan) were isolated and characterized.
The strains had diverse physiological and metabolic properties including the ability to
oxidize a wide range of carbon compounds and reduce a variety of metals. Their
temperature, salinity and pH optima varied markedly. Phylogenetic analyses of the 16S
rRNA of strain RED1 showed that the strain represented a new species of a new genus
in the domain Bacteria. The bacterium most closely related to strain RED1 is the
fermentative Fe(III)-reducer, Pelobacter acetylenicus (similarity value, 92.8%). Strain
NEF1 possesses a unique combination of phenotypic traits and a low mol % G+C.
From preliminary analyses and comparative biochemistry, NEF1 appears to be a novel
metal-reducing bacterium of the Flexistipes group.
The bacteria isolated in this study were able to grow at temperatures and salinities
consistent with the reservoir from which they were isolated. This indicated that
petroleum reservoirs are a new source of physiologically diverse, novel, metal-reducing
microorganisms. The bacteria isolated also demonstrated a number of characteristics
that would enable them to survive and persist in extreme subsurface conditions and
develop a selective ecological advantage in petroleum reservoir environments.
Significantly, the metal-reducing bacteria isolated were able to utilize an array of
metabolic products produced by bacteria indigenous to petroleum reservoirs. This has
resulted in a new proposed model for the ecological succession of bacteria in petroleum
reservoirs.
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Vilà, Brau Anna. "Anàlisi del fenotip resultant de la modificació de l’expressió del gen 3-Hidroxi-3-metilglutaril-CoA sintasa mitocondrial." Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/32118.
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La cetogènesi és el procés mitocondrial pel qual es sintetitzen els cossos cetònics (acetoacetat, 3-hidroxibutirat i acetona) a partir de l’acetil-CoA provinent de la degradació dels àcids grassos. És un procés mitocondrial i l’enzim clau de la via és la 3-hidroxi-3-metilglutaril-CoA sintasa mitocondrial (HMGCS2). La regulació de l’HMGCS2 ha estat àmpliament estudiada i es coneixen les hormones (glucagó, insulina, dexametasona), situacions metabòliques (dieta grassa, dejuni-realimentació, lactància, exercici perllongat) o patològiques (diabetis) que la regulen. Durant la darrera dècada s’atribueix als cossos cetònics un paper com a molècules senyalitzadores.
Per tal d’aprofundir en l’estudi d’aquest paper, en la present tesi doctoral ens hem plantejat estudiar les conseqüències de la modificació de l’expressió del gen HMGCS2. Amb aquest objectiu, hem realitzat experiments en cèl·lules HepG2 de sobreexpressió i disminució de l’expressió del gen HMGCS2 que ens han permès demostrar que l’HMGCS2 és necessària per la inducció de l’oxidació d’àcids grassos mitjançada per PPARα. També hem demostrat que l’HMGCS2 regula positivament l’expressió d’FGF21, un gen diana de PPARα implicat en l’homeòstasi energètica per un mecanisme que implica la sirtuina SIRT1. D’altra banda, s’ha reduït l’expressió del gen HMGCS2 en ratolins de forma aguda mitjançant la injecció d’adenovirus codificants per shRNAs i se n’ha analitzat el fenotip. S’ha identificat, mitjançant un anàlisi massiu d’expressió gènica, el gen Fat specific protein 27 (Fsp27/CIDEC), una proteïna implicada en la formació de gotes lipídiques, com a potencial gen diana de l’HMGCS2. Finalment, s’ha aprofundit en els mecanismes de regulació del gen Fsp27/CIDEC demostrant que aquest s’indueix fortament durant el dejuni a nivell hepàtic.Ketogenesis is a mitochodrial pathway by which ketone bodies (acetoacetat, 3-hydroxybutyrate and acetone) are syntesized from the acetyl- CoA comming from fatty acid oxidation. The key enzyme of this pathway is mitochondrial 3-hydroxy-3-metylglutaryl-CoA synthase (HMGCS2). The regulation of HMGCS2 has been widely studied: it is known that hormones (glucagon, insulin, dexamethasone), metabolic situations (dietary fat, fastfeeding, lactation, prolonged exercise) or pathologies (diabetes) regulate its expression. During the last decade, evidence is emerging that ketone bodies could act as signaling molecules. To further study this role, in this thesis we studied the consequences of the modification of HMGCS2 gene expression. To this end, we performed experiments in HepG2 cells by overexpression and down regulation of HMGCS2 gene, which allowed us to demonstrate that HMGCS2 is necessary for the induction of fatty acid oxidation mediated by PPARα. We have also shown that HMGCS2 positively regulates the expression of FGF21, a PPARα target gene involved in energy homeostasis by a mechanism that involves sirtuin SIRT1. On the other hand, we have down regulated HMGCS2 acutely in mice by injection of adenovirus encoding for shRNAs and we have analysed the phenotype of these mice. Through a massive analysis of gene expression, we have identified Fat specific protein 27 (Fsp27/CIDEC), a protein involved in the formation of lipid droplets, as a potential target of HMGCS2. Finally, we explored the mechanisms of Fsp27/CIDEC gene regulation demonstrating that it is strongly induced during fasting in liver.
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Button, Norman Francis. "An investigation of the clinical manifestations of the disturbances of corneal metabolic processes during contact lens wear." Thesis, Glasgow Caledonian University, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377548.
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Rocha, Andrea M. "Computational Discovery of Phenotype Related Biochemical Processes for Engineering." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3315.
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Application of bioengineering technologies for enhanced biological hydrogen production is a promising approach that may play a vital role in sustainable energy. Due to the ability of several naturally occurring microorganisms to generate hydrogen through varying metabolic processes, biological hydrogen has become an attractive alternative energy and fuel source.
One area of particular interest is the production of biological hydrogen in organically-rich engineered systems, such as those associated with waste treatment. Despite the potential for high energy yields, hydrogen yields generated by bacteria in waste systems are often limited due to a focus on microbial utilization of organic material towards cellular growth rather than production of biogas. To address this concern and to improve upon current technological applications, metabolic engineering approaches may be applied to known hydrogen producing organisms. However, to successfully modify metabolic pathways, full understanding of metabolic networks involved in expression of microbial traits in hydrogen producing organisms is necessary.
Because microbial communities associated with hydrogen production are capable of exhibiting a number of phenotypes, attempts to apply metabolic engineering concepts have been restricted due to limited information regarding complex metabolic processes and regulatory networks involved in expression of microbial traits associated with biohydrogen production.
To bridge this gap, this dissertation focuses on identification of phenotype-related biochemical processes within sets of phenotype-expressing organisms. Specifically, through co-development and application of evolutionary genome-scale phenotype-centric comparative network analysis tools, metabolic and cellular components related to three phenotypes (i.e., dark fermentative, hydrogen production and acid tolerance) were identified. The computational tools employed for the systematic elucidation of key phenotype-related genes and subsystems consisted of two complementary methods. The first method, the Network Instance-Based Biased Subgraph Search (NIBBS) algorithm, identified phenotype-related metabolic genes and subsystems through comparative analysis of multiple genome-scale metabolic networks. The second method was the multiple alignments of metabolic pathways for identification of conserved metabolic sub-systems in small sets of phenotype-expressing microorganisms. For both methodologies, key metabolic genes and sub-systems that are likely to be related to hydrogen production and acid-tolerance were identified and hypotheses regarding their role in phenotype expression were generated. In addition, analysis of hydrogen producing enzymes generated by NIBBS revealed the potential interplay, or cross-talk, between metabolic pathways.
To identify phenotype-related subnetworks, three complementary approaches were applied to individual, and sets of phenotype-expressing microorganisms. In the first method, the Dense ENriched Subgraph Enumeration (DENSE) algorithm, partial "prior knowledge" about the proteins involved in phenotype-related processes are utilized to identify dense, enriched sets of known phenotype-related proteins in Clostridium acetobutylicum. The second approach utilized a bi-clustering algorithm to identify phenotype-related functional association modules associated with metabolic controls of phenotype-related pathways. Last, through comparison of hundreds of genome-scale networks of functionally associated proteins, the á, â-motifs approach, was applied to identify phenotype-related subsystems.
Application of methodologies for identification of subnetworks resulted in detection of regulatory proteins, transporters, and signaling proteins predicted to be related to phenotype-expression. Through analysis of protein interactions, clues to the functional roles and associations of previously uncharacterized proteins were identified (DENSE) and hypotheses regarding potentially important acid-tolerant mechanisms were generated (á, â-motifs). Similar to the NIBBS algorithm, analysis of functional modules predicted by the bi-clustering algorithm suggest cross-talk is occurring between pathways associated with hydrogen production.
The ability of these phenotype-centric comparative network analysis tools to identify both known and potentially new biochemical process is important for providing further understanding and insights into metabolic networks and system controls involved in the expression of microbial traits. In particular, identification of phenotype-related metabolic components through a systems approach provides the underlying foundation for the development of improved bioengineering technologies and experimental design for enhanced biological hydrogen production.
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Bracamonte, Seraina Emilia. "Immune and metabolic processes jointly contribute to susceptibility to invasive parasites - The case of Anguillicola crassus in eels." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/21074.
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Die Einschleppung gebietsfremder Parasiten durch den Menschen ist einer der Hauptgründe für das Auftreten neuer Krankheiten in the letzten Jahrzehnten. Neue Wirte sind oftmals anfälliger für diese invasiven Parasiten als die ursprünglichen Wirte. In schwerwiegenden Fällen können invasive Parasiten zu Massensterben und zum Aussterben ihrer neuen Wirte führen. Der ursprüngliche Wirt des Aalparasiten Anguillicola crassus ist der Japanische Aal. In den frühen 1980er Jahren wurde der Parasit in die Population des Europäischen Aals eingeschleppt. Er ist einer der Faktoren, die für den Populationsrückgang des Europäischen Aals verantwortlich sind. Die molekularen Prozesse, die zur stärkeren Anfälligkeit des Europäischen Aals im Vergleich zum Japanischen Aal führen, sind noch nicht zureichend bekannt. Die Analyse transkriptomweiter differenzieller Genexpression von Immungewebe ergab, dass im Europäischen Aal sowohl Immun- als auch Nichtimmungene differenziell exprimiert waren. Dies war im Japanischen Aal nicht der Fall und deutet darauf hin, dass der Europäische Aal eine ineffiziente und kostspielige Immunantwort auslöst. Die Resultate ensprechen jenen die schon in anderen Wirbeltierwirt-invasiven Parasiten-Systemen beobachtet wurden. Ausserdem stützen diese Resultate die Hypothese, dass neuen Wirten eine wirksame Immunantwort fehlt und sie deuten darauf hin, dass Nichtimmunprozesse wesentlich zur höheren Anfälligkeit von neuen Wirten beitragen. Als Reaktion of die negativen Fitnesseffekte können neue Wirte Abwehrmechanismen entwickeln. Im Europäischen Aal entspricht das der Einkapselung von A. crassus. Einkapselung führte zu eine niedrigere Abundanz adulter A. crassus. Dies deutet darauf hin, dass das Einkapseln sich positiv auf die Gesundheit infizierter Aale auswirkt. Jedoch war die Abundanz zweier nativer Parasiten höher in Aalen, die A. crassus einkapselten. Eine verbesserte Abwehr des eingeschleppten Parasiten könnte daher die Abwehr nativer Parasiten beeinträchtigen.The human-mediated translocation of non-native parasites into foreign regions is one of the primary factors for the emergence of new diseases in recent decades. Novel hosts are often more susceptible to these invasive parasites than the native host. In severe cases, invasive parasites can lead to population declines and extinctions of their novel hosts. The eel parasite Anguillicola crassus is native to the Japanese eel. In the early 1980s it was introduced into the European eel population and is now considered to be one factor contributing to the population decline of its novel host. The underlying molecular processes determining higher susceptibility in the European eel compared to the Japanese eel are not well understood. Using whole-transcriptome differential gene expression analysis of immune organs, I found that genes involved in both immune and non-immune processes were differentially expressed in the European eel but not the Japanese eel, suggestive of an ineffective and costly immune response in the former. These results are in line with those observed between susceptible and resistant hosts in other vertebrate host-invasive parasite systems. Furthermore, the results support the hypothesis that novel hosts lack an effective immune response. The results also suggest that alteration of non-immune processes contributes substantially higher susceptibilities of novel hosts. In response to the negative fitness effects of invasive parasites, novel hosts can evolve coping mechanisms. The European eel has the capacity to encapsulate and kill A. crassus. Using natural infections, I found a lower abundance of adult A. crassus, the most costly parasitic stage in those eels encapsulating the parasite, suggesting that encapsulation can potentially improve health of infected eels. At the same time, the abundance of two native parasites was higher in those eels encapsulating A. crassus. Thus, coping with A. crassus may come at the expense of coping with native parasites.
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Santos, Jorge Miguel Martins. "Understanding the microbial ecology and ecophysiology of enhanced biological phosphorus removal processes through metabolic modelling and experimental studies." Master's thesis, Faculdade de Ciências e Tecnologia, 2013. http://hdl.handle.net/10362/12214.
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Dissertation to obtain the degree of Master in Chemical and Biochemical EngineeringThe enhanced biological phosphorus removal (EBPR) process in activated sludge systems has become a widely applied wastewater treatment technology to control eutrophication. The success of this process relies on the sludge enrichment with polyphosphate accumulating organisms (PAOs), while one of the main causes for its failure is due to microbial competition between PAOs and another group of organisms known as the glycogen accumulating organisms (GAOs). The microbial ecology and ecophysiology of these two groups have been investigated through metabolic modelling and experimental studies in order to provide a better understanding of EBPR systems. This thesis focuses on researching the P removal efficiency and metabolic behaviour of an enriched culture containing two PAOs: Tetrasphaera-related organisms and Accumulibacter, which were acclimatized with casamino acids as sole carbon source in a sequencing batch reactor (SBR). Both organisms were identified through fluorescence in situ hybridization (FISH), and this culture demonstrated anaerobic P release, glycogen hydrolysis, a very low poly--hydroxyalkanoates (PHA) synthesis and high casamino acids uptake; followed by aerobic P uptake, glycogen formation and a very low PHA oxidation. Different carbon sources (glucose, acetate, propionate, glutamate, aspartate, glycine and casamino acids) were studied through batch tests inoculated with sludge from the main SBR. Through experimental data, it was suggested that Accumulibacter were responsible for the uptake of volatile fatty acids (VFAs), and Tetrasphaera-related organisms were likely responsible for both glucose and amino acids uptake. This thesis also focuses on the development of a model that combines a PAO-GAO metabolic model with activated sludge model no. 2d (ASM2d) in collaboration with Hydromantis Environmental Software Solutions, Inc.. The combined model was implemented in the GPS-X software and will provide a new and advanced platform for wastewater treatment modelling, which will be available to practitioners.
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DeGroat, Ashley R., and Jonathan M. Peterson. "THE EFFECT OF ALCOHOL CONSUMPTION ON FEMALE INFLAMMATION." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/66.
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INTRODUCTION: Alcoholic cirrhosis occurs at a higher rate in female patients, at an earlier age, and with a lower consumption of alcohol compared to male patients. In our study on alcoholic fatty liver disease (AFLD) and adipokine levels, female mice showed a 50% higher mortality rate compared to ethanol fed male mice. The amount of ethanol consumed was similar between sexes when normalized to body weight. This resulted in our hypothesis that female mice are more susceptible to inflammation caused by alcohol consumption. METHODS: 12-week old female mice were fed a Lieber-Decarli alcohol diet (5% ETOH by volume) for 6-weeks and body weight and food intake were measured daily. Serum was collected from the mice and alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum triglycerides, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels were measured with the appropriate assays. RESULTS: In response to alcohol feeding, female mice showed significant increases in levels of ALT and AST compared to the male mice, indicating increased damage to the liver. TNF-α and IL-6 were also significantly increased in the ethanol fed female mice, indicating a significant increase in inflammation compared to the male ethanol fed mice. There was no difference found in the levels of serum triglycerides. CONCLUSION: These results indicate chronic alcohol consumption affects mice in a sex dependent manner, and that female mice are more susceptible to the adverse effects of alcohol than male mice. Increased female susceptibility to ethanol-induced damage must be considered in future ethanol-feeding studies.
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Muller, Ashley George. "The effects of nanomaterials, in the presence and absence of serum proteins, on testicular cell metabolic processes and steroidogenesis." Thesis, University of the Western Cape, 2014. http://hdl.handle.net/11394/4143.
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Magister Scientiae (Medical Bioscience) - MSc(MBS)The aim of this study is to be the first to ascertain the effects of silver nanoparticles on testosterone production. The Ag NPs used for this study have the following characteristics; purity ≥ 99.5%; 66.7 % of particles have a diameter between 20-40 nm in aqueous solution. Three month old male Balb/C mice were sacrificed and testicular cell cultures were prepared. The cells were subsequently treated with various concentrations of Ag NPs (with or without luteinizing hormone (LH)-treatment) and incubated for 4 hours. Testosterone secretion in the culture supernantant was then determined using a testosterone ELISA kit. Ag NPs (at 20 μg/ml) significantly (p < 0.001) decreased LH-stimulated testosterone production as compared to the control. This study showed that Ag NPs adversely affect testosterone synthesis in vitro and can therefore pose a risk for male reproduction.
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Kleist, Sarah Alessandra [Verfasser], and Dietmar [Akademischer Betreuer] Schomburg. "Metabolic adaptation processes of the marine bacterium Dinoroseobacter shibae DFL12T to changing environmental conditions / Sarah Alessandra Kleist ; Betreuer: Dietmar Schomburg." Braunschweig : Technische Universität Braunschweig, 2016. http://d-nb.info/1175818453/34.
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Prasai, Madhu Janina. "The effect of obesity on diurnal variation in cardiovascular and metabolic processes in a mouse model of diet-induced obesity." Thesis, University of Leeds, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.582132.
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Physiological processes display intrinsic circadian variations which are controlled by an endogenous circadian timing mechanism. Metabolic disease comprising type 2 diabetes and obesity is a recognised risk factor for cardiovascular disease (CVD). The early phase of atherosclerotic CVD is endothelial dysfunction and, like pre- diabetic insulin resistance, is a major focus of study. Metabolic and vascular disease may be linked through insulin resistance, which is now recognised to be a critical risk factor for the development both of endothelial dysfunction and of type 2 diabetes. A circadian component to cardiovascular and metabolic disease is evident from observations of human populations and recently critical animal studies have begun to elucidate the underlying mechanism. It is not known if circadian dysfunction is a central feature of acquired cardiometabolic disease, or if so at which stage in the disease process it develops. The effect of acquired insulin resistance upon circadian variation in insulin sensitivity and insulin signalling is also unclear. In a mouse model of diet-induced obesity, it was hypothesised that obesity is associated with pathological diminution of diurnal rhythms of systemic and cellular homeostasis and that such diminution is particularly associated with the occurrence of insulin resistance. In the cardiovascular system, aortic endothelial vasomotion studies and qPCR showed no loss of rhythm in obese animals despite clear differences in endothelial phenotype between obese and lean. When the focus of investigation was shifted to other insulin-sensitive tissues, the predicted attenuation of rhythm was found, with widespread diurnal abnormalities in obesity of systemic insulin and glucose homeostasis, rhythmic transcription of clock genes and downstream clock-controlled genes important to metabolic homeostasis, including AMPK. A gradient of tissue sensitivity to circadian disruption was seen, with marked disruption in visceral adipose but fully preserved rhythms in liver and aorta. Patterns of circadian disruption closely mirrored those of tissue inflammation but did not correspond to impaired insulin signalling, which was most marked in liver, followed by aorta. These findings put circadian disruption into the context of tissue- specific events in obesity. They suggest that circadian disruption and insulin resistance arise by distinct processes and prompt speculation regarding the cellular mechanism by which circadian disruption may arise in obesity. 3
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Kleist, Sarah Alessandra Verfasser], and Dietmar [Akademischer Betreuer] [Schomburg. "Metabolic adaptation processes of the marine bacterium Dinoroseobacter shibae DFL12T to changing environmental conditions / Sarah Alessandra Kleist ; Betreuer: Dietmar Schomburg." Braunschweig : Technische Universität Braunschweig, 2016. http://nbn-resolving.de/urn:nbn:de:gbv:084-16090114052.
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Warren, Zachary C., and Jonathan M. Peterson. "UPREGULATING OF CYP2E1 IN ETHANOL-FED MICE WITH TRANSGENIC OVEREXPRESSION OF CTRP3." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/60.
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INTRODUCTION: The liver is the primary organ responsible for the removal of toxic substances from the body by means of a variety of metabolic pathways. One class of proteins responsible for much of the body’s xenobiotic drug and alcohol metabolism is the Cytochrome P450 family of proteins. One protein, Cytochrome P450 Class E Subclass 2 (Cyp2E1), has an integral role in alcohol metabolism by the liver. Cyp2E1 becomes fully activated after an organism has consumed excessive amounts of alcohol excessive alcohol and works with aldehyde dehydrogenase (ALDH) to metabolize ethanol to acetaldehyde. Another metabolic protein, C1q TNF Related Protein 3 (CTRP3), has been shown to effectively prevent alcoholic fatty liver disease (AFLD), specifically with long-term alcohol-induced lipid accumulation.
METHODS: In this experiment, 12-week old male mice were fed a Lieber-Decarli alcohol diet (5% ETOH by volume) for 6-weeks. The food intake and body weight of the mice was recorded each day. The mice in the experiment included both wild type and transgenic CTRP3 overexpressing mice. At the end of the 6-week period the mice were euthanized, and the liver was carefully removed, flash-frozen, and prepared for immunoblot analysis of the proteins.
RESULTS: Cyp2E1 levels increased significantly in response to ethanol consumption. Cyp2E1 levels were further elevated in ethanol-fed CTRP3 transgenic overexpressing mice. Cyp2E1 levels in CTRP3 transgenic mice were nearly twice that of wild type ethanol-fed mice.
CONCLUSIONS: The results of the experiment show a significant increase in Cyp2E1 in mice which overexpress CTRP3. This upregulation of Cyp2E1 with CTRP3 overexpression could explain the mechanism for reduced hepatic lipid accumulation in ethanol-fed CTRP3 transgenic mice.
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Halama, Anna Maria [Verfasser], Jerzy [Akademischer Betreuer] Adamski, Karsten [Akademischer Betreuer] Suhre, and Johann Josef [Akademischer Betreuer] Hauner. "Analyses of metabolic pathways of cellular processes in apoptosis and adipogenesis / Anna Maria Halama. Gutachter: Karsten Suhre ; Jerzy Adamski ; Johann Josef Hauner. Betreuer: Jerzy Adamski." München : Universitätsbibliothek der TU München, 2013. http://d-nb.info/1063090520/34.
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HARNISH, CHRISTOPHER R. "Comparison of Two Different Sprint Interval Training Work-to-Rest Ratios on Acute Metabolic and Inflammatory Responses." VCU Scholars Compass, 2014. http://scholarscompass.vcu.edu/etd/3565.
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High intensity exercise is believed to yield greater results on health and human performance than moderate intensity exercise. Extensive research indicates that not only do high-intensity interval training (HIT) and sprint interval training (SIT) produce significant improvements in cardiovascular fitness and disease, they may be more effective at improving long-term metabolic function, including insulin sensitivity (Si), by producing more mitochondria. Moreover, compliance rates for HIT and SIT participation are reported to be the same or better than traditional moderate intensity exercise. Because lack of time is often cited as major hindrance to exercise participation, SIT is also seen as a time efficient option to improve health and performance. It does appear, however, that repeated sessions of SIT are needed before overall improvements can be measured. SIT protocols employing maximal 30 sec sprints with ~5 min rest [a 1:9 work-to-rest ratio (W:R)], have garnered much of the research focus, while those using minimal rest periods, like Tabata which uses 20 sec sprints and 10 sec rest (2:1 W:R), have been ignored. This may omit a possible SIT option that could influence acute and chronic adaptations. The role of inflammatory cytokines on Si remains an area of continued research. While endurance exercise is thought to create an overall anti-inflammatory environment that stimulates improvement in Si, SIT is often viewed as pro-inflammatory. However, few studies have provided significant insight into cytokine release following SIT, and none haveexplored its impact on Si. In addition, the impact of W:R on cytokine remains speculative at best. Therefore, the examination of the effect of different sprint protocols of similar total work (kJ) on performance, metabolic function, and inflammatory response may provide valuable insight into these adaptive processes.
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Bracamonte, Seraina Emilia [Verfasser], Justyna [Gutachter] Wolinska, Michael [Gutachter] Monaghan, and Emanuel [Gutachter] Heitlinger. "Immune and metabolic processes jointly contribute to susceptibility to invasive parasites - The case of Anguillicola crassus in eels / Seraina Emilia Bracamonte ; Gutachter: Justyna Wolinska, Michael Monaghan, Emanuel Heitlinger." Berlin : Humboldt-Universität zu Berlin, 2020. http://d-nb.info/1206588233/34.
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Lavallée, Bernard. "Modélisation de comportements transitoires de la biomasse dans les procédés de boues activées à l'aide d'un modèle métabolique : Modelling of transient behavior of active biomass in activated sludge processes using a metabolic model." Doctoral thesis, Université Laval, 2009. http://hdl.handle.net/20.500.11794/21024.
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Les modèles de boues activées ASM 1, 2 et 3 de l’International Water Association (IWA) sont acceptés comme la norme dans l’industrie du traitement des eaux usées. Toutefois, plusieurs auteurs ont remarqué que les constantes cinétiques de ces modèles dépendent du type de substrat, de la configuration du procédé et de l’âge des boues. Dans ces modèles, la répartition des flux de substrat entre la croissance et le stockage est une fonction empirique.Certains auteurs ont indiqué que les constantes cinétiques des modèles de boues activées peuvent être influencés par la régulation de la production d’enzymes. Ainsi, un ingénieur cherchant à modifier un système spécifique ne peut prédire la réponse du système réel une fois les modifications apportées, ni choisir la bonne configuration ou les bonnes modifications avec le même ensemble de constantes cinétiques. Il y a 60 ans, Monod (1949) a proposé d’appliquer l’équation de Michaelis-Menten décrivant la cinétique enzymatique à une culture de microorganismes. Afin de simplifier la relation mathématique proposée, Monod (1949) réduit la cellule entière en un seul enzyme génétiquement exprimé à une seule intensité. Toutefois, le métabolisme de la cellule est basé sur un grand nombre de réactions biochimiques. Le chapitre 2 de ce travail revoit la littérature afin d’identifier les facteurs contrôlant le métabolisme de la cellule et la régulation de l’activité spécifique de la cellule. La revue de la littérature a été rédigée de façon à souligner les mécanismes de régulation qui induisent une variation du taux de croissance afin de les exprimer mathématiquement (dµ/dt). L’étude de ces mécanismes vise à modéliser la variation de l’activité spécifique. La revue est limitée aux organismes procaryotes hétérotrophes sous des conditions aérobies. Dans la littérature, des modèles cybernétiques ont été proposés pour modéliser la croissance cellulaire et portent, entre autres, sur la régulation de la production d’enzymes, c’est-à-dire sur l’induction. L’objectif de ce travail est donc de présenter un modèle de boues activées qui imite l’induction enzymatique de la biomasse active dans le cadre des modèles de boues activées. Dans le modèle proposé au chapitre 3, les taux de réaction peuvent s’ajuster aux conditions environnementales et à l’historique cellulaire. Dans un premier temps, le modèle théorique a été calé sur les données trouvées dans la littérature. Les données colligées lors d’expériences transitoires à court et à long terme ont toutes été modélisées avec le même ensemble de constantes cinétiques, ce qui n’était pas possible avec les autres modèles. Le modèle proposé offre ainsi un regard plus réaliste de l’activité spécifique de la biomasse active sous des conditions d’opération du procédé hautement variables. Dans un deuxième temps, un protocole expérimental est proposé pour évaluer l’état métabolique des microorganismes présents dans la boue activée, et évaluer la performance du modèle proposé. Le protocole a été conçu pour caractériser l’évolution de plusieurs composants intracellulaires au cours de comportements transitoires de la biomasse. Au chapitre 5, le modèle théorique proposé au chapitre 3 a été adapté au protocole expérimental et calé sur les données expérimentales obtenues. Au cours des expériences effectuées, une réduction temporaire de l’activité métabolique a été observée après que la capacité de stockage ait été comblée. Selon les simulations effectuées, et la concordance des résultats obtenus avec une revue de littérature approfondie, il semble que la régulation croisée du carbone et de l’azote puisse être utilisée pour modéliser certains comportements transitoires et la régulation des flux métaboliques vers la croissance et le stockage. Au chapitre 6, les modèles à strucuture ARN-r sont proposés afin de donner une description de l’état métabolique des microorganismes à l’aide de nouvelles techniques moléculaires et prédire l’accélération de la croissance (dµ/dt) de la boue activée. Dans ces modèles, la synthèse du système de synthèse des protéines (PSS) est décrite par un mécanisme autocatalytique. La cinétique du processus autocatalytique présente un fondement métabolique de l’accélération de la croissance et de la phase de latence. Les modèles ARN-r sont en mesure de décrire adéquatement l’accélération de la croissance pour différentes configurations de réacteurs. Ainsi, ce type de modèles fait appel à des constantes cinétiques à caractère «intrinsèque» et peut être utilisé de façon moins restrictive que les modèles à caractère plus empirique. Ceci constitue un avantage pour le développement de modèles de conception plus fiables.For wastewater treatment, the activated sludge models (ASMs) 1, 2, and 3 of the International Water Association (IWA) are accepted as industrial standard. However, many authors have observed that the kinetic parameters of these models depend on the type of substrate, process configuration, and sludge age. Some publications showed that the kinetic parameters of ASMs could be influenced by regulation of enzyme production. In the models currently used to describe the activated sludge process, the distribution of the substrate flux between growth and storage is an empirical function. Therefore, an engineer aiming to make some modifications to a specific treatment system is not able to predict the response of the real system after the modifications and choose the right configuration or modifications with the same set of parameters. Sixty years ago, Monod (1949) proposed the application of the Michaelis Menten relation describing enzyme kinetics to a culture of micro-organisms. For the purpose of simplification, the mathematical relation proposed by Monod (1949) reduced the entire cell to a single enzyme genetically expressed at a single level. However, cell metabolism is based on a large number of biochemical reactions. Chapter 2 of this thesis reviews the literature to identify the controlling factors of cell metabolism and the regulation of the specific activity of the cell. The literature review was designed to highlight which regulation mechanisms induce a growth rate variation so that they can be expressed mathematically (dµ/dt). The study of these processes will focus on modeling the specific activity variation. The review is limited to heterotrophic prokaryote organisms growing under aerobic conditions. Cybernetic models are proposed for modeling cell growth and focus, among other things, on regulation of enzyme production, that is to say on induction. The objective of this work is to present an activated sludge model that mimics the enzymatic induction of active biomass within the framework of ASMs. In the proposed model presented in chapter 3, process rates are modulated according to the environmental conditions and cell history. In a first step, the model was fitted on the basis of data found in the literature. All data collected from short and long transient experiments were fitted with the same set of parameters, which was not possible with various models. The proposed model gave a more realistic picture of active biomass and of its specific activity under highly varying process conditions. In a second step, an experimental protocol is presented to perform the evaluation of the structured biomass model. The protocol was designed to induce transient behaviour and characterize the evolution of several internal biomass components. In chapter 5, the theoretical model proposed in chapter 3 is adapted to an experimental protocol and fitted to the collected data. In these experiments it was observed that filling the storage capacity of cells leads to special transient behaviour and a temporarily reduced metabolic activity. The model-based interpretation of the results showed that the observed transient behaviour can be explained by cross-regulation of carbon and nitrogen metabolism. Hence, according to an extensive literature review, the cross-regulation of carbon and nitrogen can be used to model some observed transient behavior and regulation of the storage process in activated sludge. In chapter 6, rRNA-structured biomass models are proposed to describe the metabolic status of cells using new molecular techniques in view of predicting the growth response (dµ/dt) of cells in the activated sludge process. The autocatalytic reaction rate of the synthesis of the PSS component (rRNA) can provide a mechanistic explanation for the growth response and the growth lag phase. The proposed models were able to properly describe and predict the growth response of the biomass in various types of reactor. Such models could be more widely applicable by using intrinsic model parameters, and this could be a key improvement as it could lead to improved models for design.
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Panji, Sumir. "Identification of bacterial pathogenic gene classes subject to diversifying selection." Thesis, University of the Western Cape, 2009. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_5842_1297942831.
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Availability of genome sequences for numerous bacterial species comprising of different bacterial strains allows elucidation of species and strain specific adaptations that facilitate their survival in widely fluctuating micro-environments and enhance their pathogenic potential. Different bacterial species use different strategies in their pathogenesis and the pathogenic potential of a bacterial species is dependent on its genomic complement of virulence factors. A bacterial virulence factor, within the context of this study, is defined as any endogenous protein product encoded by a gene that aids in the adhesion, invasion, colonization, persistence and pathogenesis of a bacterium within a host. Anecdotal evidence suggests that bacterial virulence genes are undergoing diversifying evolution to counteract the rapid adaptability of its host&rsquo
s immune defences. Genome sequences of pathogenic bacterial species and strains provide unique opportunities to study the action of diversifying selection operating on different classes of bacterial genes.
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Rungapamestry, Vanessa. "The metabolic fate of glucosinolates from processed brassica vegetables after consumption." Thesis, Robert Gordon University, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.436351.
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Tappi, Silvia <1980>. "Qualitative, Metabolic and Nutritional Aspects of Traditional and Innovative Minimally Processed Fruit." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amsdottorato.unibo.it/7633/.
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Minimally processed fruit (MPF) are products that have to maintain their quality similar to those of fresh ones. Being metabolic active tissues, they show physical and physiological response to minimal processing (wounding), that negatively influence their shelf-life. In the last decades, novel non-thermal processing methods have attracted the interest of food scientists, industries and consumers as technologies useful for shelf-life extension or increasing product functionality, with a minimal impact on the nutritional and sensory properties of foods. The main aim of this PhD thesis was to investigate qualitative, metabolic and nutritional aspects of different MPF, submitted to traditional and innovative non-thermal processes. This issue was addressed considering the product as a dynamic system, both in terms of endogenous physiological activity and porous matrix interacting with the surrounding ambient (during processing and storage), through the application of multi-analytical approach. The most consistent results related to the applied non-thermal techniques confirmed their different potentiality in the optic of processing and product innovation, but the need of their modulation in relation to the different raw material susceptibility to degradation and final product target. Cold plasma treatment effects on fresh-cut fruit, characterized by different kind of stability criticisms, resulted mainly bound to the inactivation of degradative enzymes and microbial cells, without evidencing functional modifications in the final products. The study of osmotic dehydration and vacuum impregnation highlighted as these techniques can be successfully applied for cold formulation/enrichment of MPF, but also the necessity to carefully account for the metabolic and structural modifications induced by the processing on the vegetable tissues. An induction of metabolic stress response was also evidenced as a consequence of pulsed electric fields treatment related to electric field strength. Below the threshold limit of irreversible damages to cell membranes, the treatment promoted only slight and reversible modifications of the metabolic profiles.
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Tolliver, Benjamin M., Devaiah P. Shivakumar, and Cecelia A. McIntosh. "Effects of Amino Acid Insertion on the Substrate and Regiospecificity of a Citrus paradisi Glucosyltransferase." Digital Commons @ East Tennessee State University, 2014. https://dc.etsu.edu/etsu-works/345.
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Glucosyltransferases, or GTs, are enzymes which perform glucosylation reactions. These glucosylation reactions involve attaching a UDP-activated glucose molecule to acceptor molecules specific to the enzyme. The products of these reactions are observed to have a myriad of effects on metabolic processes, including stabilization of structures, solubility modification, and regulation of compound bioavailability. The enzyme which our lab focuses its research on is a flavonol-specific 3-O-GT found in Citrus paradisi, or grapefruit. This enzyme is part of the class of enzymes known as flavonoid GTs, which are responsible for, among other things, the formation of compounds which can affect the taste of citrus. Our lab focuses its research on performing site-directed mutagenesis on Citrus paradisi 3-O-GT in an attempt to modify its substrate specificity and regiospecificity. In this poster, we report our findings thus far concerning the addition of specific residues to the 3-O-GT's amino acid sequence based on an alignment with the sequence of a putative flavonoid GT found in Citrus sinensis.
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Simnett, Sarah Jacqueline. "Relaxation processes in cardiac muscle." Thesis, University of Oxford, 1993. http://ora.ox.ac.uk/objects/uuid:9b670123-f816-42be-8d74-c37917af200b.
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Delahunty, Jane S. "Co-ordination of carboxylation and decarboxylation processes in the CAM plant Ananas comosus." Thesis, University of Newcastle Upon Tyne, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275596.
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Tolliver, Benjamin M., Devaiah P. Shivakumar, and Cecelia A. McIntosh. "Effects of Amino Acid Sequence Insertion on the Substrate Preference of a Citrus Paradisi Glucosyltransferase." Digital Commons @ East Tennessee State University, 2013. https://dc.etsu.edu/etsu-works/347.
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Glucosyltransferases (GTs) are enzymes which perform glucosylation reactions, which involve attaching a UDP-activated glucose molecule to acceptor molecules specifi c to the enzyme. The enzyme which our lab focuses its research on is a fl avonol-specifi c 3-OGT found in Citrus paradisi, or grapefruit (Cp3GT). This enzyme is part of the class of enzymes known as fl avonoid GTs, which are responsible for, among other things, the formation of compounds which can affect the taste of citrus. Our lab focuses its research on performing site-directed mutagenesis on Cp3GT in an attempt to discover the residues important for substrate and regiospecifi city. In this study, we are testing the basis of substrate septicity of Cp3GT. We hypothesize that incorporation of fi ve amino acids specifi c to Citrus sinensis GT (CsGT) into Cp3GT at 308th position may facilitate mCp3GT to use anthocyanidins as one of the substrates. We report our fi ndings thus far concerning the addition of specifi c residues to the Cp3GT’s amino acid sequence based on an alignment with the sequence of a putative fl avonoid GT found in Citrus sinensis.
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Erhardt, Sophie. "Importance of endogenous kynurenic acid in brain catecholaminergic processes and in the pathophysiology of schizophrenia /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4889-5/.
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Patel, Gajendra. "Implementing and Evaluating MQLAIP: A Metabolism Query Language." Case Western Reserve University School of Graduate Studies / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=case1289591644.
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Farrar, S. C. "Carbon allocation in barley plants." Thesis, Bangor University, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378352.
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Björkman, Frida. "Snusets effekter på aeroba processer och energiomsättning under fysiskt arbete." Thesis, Gymnastik- och idrottshögskolan, GIH, Institutionen för idrotts- och hälsovetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-1828.
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Syftet med föreliggande studie var att undersöka effekterna av ett längre uppehåll från tobaks- och nikotinbruk på maximal aerob effekt och energiomsättning under submaximalt arbete hos regelbundet snusande personer. Metod 23 snusare (18 män, 5 kvinnor) undersöktes före och efter >6 veckors uppehåll från snus (SSP). Försökspersonerna genomförde ett stegrande submaximalt arbete på cykelergometer, ett maximalt löptest och ett uthållighetsarbete bestående av 60 minuter cykling på 50 % av VO2max. Syreupptag (VO2), ventilation (VE), subjektivt skattad ansträngning på Borgs RPE-skala (RPE), hjärtfrekvens (HF) och blodtryck (BT) mättes. Blodprov togs för analys av kotinin, laktat [HLa], blodglukos och fria fettsyror (FFA) i vila och under arbete. Resultat Submaximalt VO2 och energiomsättning påverkades inte av >6 veckors uppehåll från snus. VE, respiratorisk kvot (RQ), blodglukos och RPE var oförändrade under det stegrande submaximala arbetet. Post-SSP sågs däremot en viss förändring i koncentrationen av [HLa], genom signifikant lägre [HLa] under den sista arbetsbelastningen (7,61 ± 3,01 resp. 7,18 ± 2,95 mmol/l, p<0,05). HF och BT var signifikant lägre vid alla submaximala arbetsbelastningar. Genomsnittlig löptid i det maximala testet, uppnått maximalt syreupptag (VO2max), maximal HF och [HLa] var i princip identiska före och efter uppehåll från snus. Under långtidsarbetet var FFA, HF och BT signifikant lägre och det fanns en tendens till lägre ventilatorisk drift post-SSP. Det fanns ingen signifikant påverkan på övriga mätningar under långtidsarbetet. Andra observerade fysiologiska förändringar var viktökning (1,5 ± 1,6 kg, p<0,01) och sänkt HF i vila (61 ± 9 slag/min pre-SSP, 55 ± 8 slag/min post-SSP, p<0,05). Slutsats Syreupptagning vid submaximalt aerobt arbete som involverar stora muskelgrupper påverkas inte av ett längre uppehåll från regelbundet snusbruk. VO2max och maximal aerob prestationsförmåga var oförändrade. Exponering för snus kan ha en viss inverkan på metabolismen under arbete, vilket främst visades genom lägre koncentrationer av FFA post-SSP.The aim of the present study was to examine the effects of a prolonged cessation from tobacco and nicotine on maximal aerobic power and energy metabolism during submaximal exercise in regular snuff users. Methods 23 snuff users (18 men, 5 women) were investigated before and after a >6 week snuff cessation period (SCP). Participants performed a submaximal graded exercise test on cycle ergometer, a maximal running test and a prolonged aerobic endurance test consisting of 60 minutes cycling on 50 % of VO2max. Measurements of oxygen uptake (VO2), ventilation (VE), rate of perceived exertion on Borg´s RPE-scale (RPE), heart rate (HR) and blood pressure (BP) were obtained. Blood samples were drawn for analysis of cotinine, lactate [HLa], blood glucose, and free fatty acids (FFA) at rest and during exercise. Results Submaximal VO2 and energy expenditure were not affected by >6 weeks of withdrawal from snus. VE, respiratory exchange ratio (RER), blood glucose and RPE during submaximal graded exercise test remained unchanged. However, post-SCP a small change was observed in the [HLa] concentration, due to a significantly lower [HLa] at the final stage in the test (7.61 ± 3.01 and 7.18 ± 2.95 mmol/l, respectively, p<0.05). HR and BP were significantly reduced at all submaximal work rates. Mean time to exhaustion during the maximal running test, maximal oxygen uptake (VO2max), maximal HR and [HLa] were almost identical before and after SCP. Significantly lower values of FFA, HR and BP, and a tendency towards lower ventilatory drift during prolonged submaximal exercise were observed post-SCP. No changes were observed on any other measurements during the prolonged exercise test. Other physiological changes were weight gain (1.5 kg ± 1.6 kg, p<0.01) and decreased HR (61 ± 9 beats/min pre-SCP, 55 ± 8 beats/min post-SCP, p<0.05) at rest. Conclusions Oxygen uptake in submaximal aerobic exercise with large muscle groups is not affected by a prolonged cessation from regular snuff dipping. VO2max and maximal aerobic performance is unchanged. Exposure to snus may have some influence on the metabolism during exercise, mainly characterized by lower concentrations of FFA post-SCP.
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O'Donnell, Brynn Marie. "The Flow Regime of Function: Influence of flow changes on biogeochemical processes in streams." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/101660.
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Streams are ecosystems organized by disturbance. One of the most frequent disturbances within a stream is elevated flow. Elevated flow can both stimulate ecosystem processes and impede them. Consequently, flow plays a critical role in shifting the dominant stream function between biological transformation and physical transportation of materials. To garner further insight into the complex interactions of stream function and flow, I assessed the influence of elevated flow and flow disturbances on stream metabolism. To do so, I analyzed five years of dissolved oxygen data from an urban- and agriculturallyinfluenced stream to estimate metabolism. Stream metabolism is estimated from the production (gross primary production; GPP) and consumption (ecosystem respiration; ER) of dissolved oxygen. With these data, I evaluated how low and elevated flows differentially impact water quality (e.g., turbidity, conductivity) and metabolism using segmented metabolism- and concentration- discharge analyses. I found that GPP declined at varying rates across discharge, and ER decreased at lower flows but became constant at higher flows. Net ecosystem production (NEP; = GPP - ER) reflected the divergence of GPP and ER and was unchanging at lower flows, but declined at higher discharge. These C-Q patterns can consequently influence or be influenced by changes in metabolism. I coupled metabolism-Q and C-Q trends to examine linked flow-induced changes to physicochemical parameters and metabolism. Parameters related to metabolism (e.g., turbidity and GPP, pH and NEP) frequently followed coupled trends. To investigate metabolic recovery dynamics (i.e., resistance and resilience) following flow disturbances, I analyzed metabolic responses to 15 isolated flow events and identified the antecedent conditions or disturbance characteristics that most contributed to recovery dynamics. ER was both more resistant and resilient than GPP. GPP took longer to recover (1 to >9 days, mean = 2.5) than ER (1 to 2 days, mean = 1.1). ER resistance was strongly correlated with the intensity of the flow event, whereas GPP was not, suggesting that GPP responds similarly to flow disturbances, regardless of the magnitude of flow event. Flow may be the most frequent disturbance experienced by streams. However, streams are exposed to a multitude of other disturbances; here I also highlight how anthropogenic alterations to streams – namely, burying a stream underground – can change biogeochemical function. This thesis proposes novel frameworks to explore the nexus of flow, anthropogenic disturbances, and stream function, and thereby to further our understanding of the complex relationship between streams and disturbances.Master of Science
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Yang, Zhiliang. "Metabolic and Process Engineering of Pichia Pastoris for the Production of Value-added Products." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/37014.
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Motivated by the surging demand of recombinant proteins and biofuels derived from renewable substrates, increasing attention has been paid to the development of novel strains via metabolic engineering strategies. Pichia pastoris is a eukaryotic platform suitable for protein expression and potentially for biofuel production due to its advantageous traits over Escherichia coli or Saccharomyces cerevisiae. In this thesis, we constructed a xylanase-producing P. pastoris strain. The fungal xylanase Xyn11A was successfully overexpressed under the constitutive GAP promoter. Biochemical characterization of the xylanase revealed that Xyn11A is optimally active at 70 °C and pH 7.4. This xylanase was stable over a wide range of pH ranging from pH 2 to pH 11. Excellent thermal stability was observed at temperature 60 °C. Enhanced production of Xyn11A was achieved by investigating the effect of carbon source and feeding strategies. The highest xylanase activity was detected at 15000 U/mL using high cell density cultivation.
Production of optically pure (2R, 3R)-2, 3-BD was achieved by engineering P. pastoris with a heterologous pathway. The pathway genes consisting of Bacillus subtilis alsS, alsD and S. cerevisiae BDH1 were assembled and transformed into P. pastoris. Cultivation conditions were optimized and the highest titer of 2, 3-BD obtained using YPD media was 45 g/L in fed-batch cultivation. To enhance the economic viability of 2, 3-BD production in P. pastoris, statistical medium optimization was performed. It was found that 75 g/L of 2, 3-BD was produced using optimized media in fed-batch cultivation.
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Winders, Kyle. "Ecosystem processes of prairie streams and the impact of anthropogenic alteration on stream ecological integrity." Thesis, Kansas State University, 2010. http://hdl.handle.net/2097/6849.
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Master of ScienceDepartment of Biology
Walter K. Dodds
North America has lost more than 95% of the original tallgrass prairie because of heavy land conversion, making prairie streams some of the most endangered habitats in North America. In order to effectively manage aquatic systems and improve biotic integrity of prairie streams research is needed that assesses the ecosystem characteristics of natural systems and evaluates the influence of anthropogenic alteration. We described the ecosystem characteristics of six ephemeral headwater streams draining tallgrass prairie within the Osage Plains of southwest Missouri. NO-3-N among all sites ranged from 1.56-91.36 μg L-1, NH+4-N ranged from 5.27-228.23 μg L-1, soluble reactive phosphorus ranged from below detection (1.0 μg L-1) to 41.22 μg L-1, TN ranged from 113.82-882.89 μg L-1, and TP ranged from 8.18-158.5 μg L-1during baseflow conditions. TN:TP molar ratios ranged from 22:1 to 53:1 indicating possible P was limiting relative to N in some streams. TSS during baseflow conditions ranged from 0.27-31.80 mg L-1. Autotrophic and heterotrophic comparisons of our study sites and reference sites classified our study streams as oligo-, meso-, and eu-autotrophic (N= 1, 4, and 1, respectively) and oligo-, meso-, and eu-heterotrophic (N= 4, 1, and 1, respectively). This study suggests that good water quality and moderate heterotrophic condition, with greater GPP resulting from an open canopy, are common conditions of tallgrass prairie streams. We also investigated interactions between land use/land cover, discharge rate, hydrologic alteration, and in-stream total suspended solids concentration in 23 Kansas- Missouri streams. Most streams had break points in the TSS loading rates at discharge rates exceeded <25% of days. Our estimates showed that 88% of the total annual TSS load occurred during the 11% of days with the greatest discharge rates. Buffered streams with greater percentages of grass and/or forest riparian areas had lower breakpoint values (indicating greater discharge rates were required to transport solid particles) and lower regression intercepts, which correlated to lesser TSS concentrations relative to unbuffered streams during high discharge days. In addition, grass buffered streams had smaller flood peaks and slower rise rates and forest buffered streams had less frequent floods, which lead to less total TSS transport.
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Gorgens, Johann Ferdinand. "Quantitative yeast physiology and nitrogen metabolism during heterologous protein production." Thesis, Stellenbosch : University of Stellenbosch, 2003. http://hdl.handle.net/10019.1/16051.
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Dissertation (PhD)--University of Stellenbosch, 2003.ENGLISH ABSTRACT: QUANTITATIVE YEAST PHYSIOLOGY AND NITROGEN METABOLISM DURING HETEROLOGOUS PROTEIN PRODUCTION By Johann F. Görgens The physiology and nitrogen metabolism of the yeast, Saccharomyces cerevisiae, during heterologous xylanase production in a defined medium was quantified by the comparison of isogenic yeast strains, whereby several potential limitations in the production of the heterologous xylanase could be identified. The presence of global sensing and regulatory mechanisms, by which the yeast is able to actively regulate both heterologous gene expression and the physiological response to the process, was also investigated. The deleterious effects of heterologous xylanase production on the physiology of the recombinant host were disproportionately large with respect to the amount of foreign protein produced. The cellular processes involved in this response were identified by the transcriptional profiling of isogenic recombinant strains, in a novel analytical approach to investigating foreign protein production by S. cerevisiae. Heterologous gene expression affected a combination of cellular processes and induced the yeast stringent stress response. The corresponding loss of metabolic functionality resulted in the disproportionate physiological effects of foreign protein production, similar to previous observations in recombinant Escherichia coli, and a possible reduction in attainable production levels. Reducing the propensity of recombinant gene expression to introduce metabolic stress may therefore increase production levels of foreign proteins by yeast. The metabolic vitality of transformed strains was also reduced by the presence of multiple copies of active, plasmid-based PGK1-promoters in the cell without expression of the heterologous gene. The negative effect was caused by an increase in the biosynthetic and glycolytic capacity of the strain at the expense of other processes. Production levels of heterologous xylanase were influenced by expression vector selection and the presence of auxotrophic mutations in transformed strains of S. cerevisiae. The increased transcription levels obtained with the multicopy plasmidbased YEp-type expression system, compared to the integrative YIp-type expression system, resulted in higher levels of xylanase production. Heterologous xylanase production thus did not saturate the secretory capacity of the host strain. The genetic stability of the autoselective YEp-type expression system in long-term chemostat culture was also demonstrated. High levels of heterologous xylanase production by transformed S. cerevisiae strains containing auxotrophic markers required the stabilisation of nitrogen metabolism via saturation of yeast cells with an excess of imported amino acids. By the removal of excessive auxotrophic markers, high levels of xylanase production by a prototrophic transformant in defined medium without amino acid addition could be obtained. Heterologous xylanase production by the prototrophic transformant was further enhanced by increasing the availability of preferred amino acids or succinate in the defined medium, indicating an additional requirement for metabolic precursors and building blocks for foreign protein synthesis. Comparable levels of heterologous xylanase production were obtained in high cell density cultures of the alternative yeast, Pichia stipitis, by the proper induction of the native ADH2-promoter, the control of oxygenation, and addition of an amino acid mixture to the defined medium, indicating the presence of generic limitations in transcription, nutrient availability and the yeast biosynthetic capacity for foreign protein production by various yeasts. The presence of global sensing and regulatory mechanisms was confirmed by the physiological response of S. cerevisiae to heterologous protein production, which included the downregulation of biosynthesis and growth, and the induction of various processes involved in the stringent stress response. Additionally, heterologous xylanase production was actively regulated on a posttranscriptional level by the auxotrophic transformants in response to the level of amino acid availability. The biosynthetic capacity for foreign protein production by both recombinant S. cerevisiae and P. stiptis was also regulated in response to the physiological state of the yeast and the availability of nutrients. The presence of these regulatory mechanisms complicated the manipulation of cellular biosynthesis at will.
AFRIKAANSE OPSOMMING: KWANTITATIEWE GIS-FISIOLOGIE EN -STIKSTOF METABOLISME GEDURENDE HETEROLOË PROTEÏEN PRODUKSIE Deur Johann Ferdinand Görgens Die fisiologie en stikstof-metabolisme van die gis, Saccharomyces cerevisiae, gedurende heteroloë xilanase produksie in ‘n gedefiniëerde medium is gekarakteriseer deur isogeniese gis-rasse te vergelyk, waardeur verskeie moontlike beperkings in die produksie van die heteroloë xilanase uitgewys kon word. Die teenwoordigheid van globale sensoriese- en beheer-meganismes, wat die gis in staat stel om beide heteroloë geen uitdrukking en die fisiologiese respons op die proses aktief te reguleer, is ook ondersoek. Die nadelige effekte van heteroloë xilanase produksie op die fisiologie van die rekombinante gasheer-organisme was uitermatig groot in vergelyking met die hoeveelheid vreemde proteïen wat geproduseer is. Die sellulêre prosesse verantwoordelik vir hierdie respons is identifiseer deur die transkripsionele profiele van isogeniese rekombinante rasse te vergelyk, in ‘n nuwe analitiese benadering tot die bestudering van vreemde proteïen produksie deur S. cerevisiae. Heteroloë geen uitdrukking het ‘n kombinasie van sellulêre prosesse geaffekteer en die gis se algemene voedingstres-respons geaktiveer. Die gepaardgaande verlies aan metaboliese funksie het die uitermatige fisiologiese effek van vreemde proteïen produksie veroorsaak, soortgelyk aan vorige waarnemings met rekombinante Escherichia coli. Die haalbare produksie-vlakke is moontlik ook verlaag deur hierdie respons. ‘n Verlaging van die geneigdheid van rekombinante geen uitdrukking om metaboliese stres te veroorsaak, mag dus die produksievlakke van vreemde proteïene in gis verbeter. Die metaboliese groei-potensiaal van die getransformeerde rasse is ook verlaag deur die teenwoordigheid van etlike aktiewe kopieë van plasmied-gebaseerde PGK1-promotors in die sel, sonder uitdrukking van die heteroloë geen, deur ‘n toename in die biosintetiese en glikolitiese kapasiteit ten koste van die ander sellulêre prosesse. Die produksievlakke van heteroloë xilanase is deur die keuse van uitdrukkings-sisteem en die teenwoordigheid van autotrofiese mutasies in die getransformeerde rasse van S.cerevisiae beïnvloed. Die verhoogde transkripsie vlakke wat met die multi-kopie, plasmied-gebaseerde YEp-tipe uitdrukkingsisteem, eerder as die geïntegreerde YIp-tipe sisteem, verkry is, het tot verhoogde xilanase produksie gelei. Heteroloë xilanase produksie het dus nie die uitskeidingskapasiteit van die gasheer versadig nie. Die genetiese stabiliteit van die autoselektiewe, YEp-tipe uitdrukkingsisteem in langtermyn chemostaat-kulture is ook gedemonstreer. Hoë vlakke van xilanase produksie deur getransformeerde S. cerevisiae rasse met autotrofiese merkers het die stabilisering van die stikstof metabolisme, deur die versadiging van die sel met ingevoerde aminosure, vereis. Die verwydering van oormatige autotrofiese merkers het tot hoë vlakke van xilanase produksie deur die prototrofiese transformant in gedefinieerde medium sonder aminosuur byvoeging gelei. Heteroloë xilanase produksie deur die prototrofiese transformant kon verder verbeter word deur die byvoeging van voorkeur-aminosure of suksinaat tot die gedefinieerde medium, en ‘n addisionele behoefte aan metaboliese voorloper-molekules en bou-blokke vir vreemde proteïensintese het dus bestaan. Vergelykbare vlakke van heteroloë xilanase produksie is in kulture met hoë sel-digthede van die alternatiewe gis, Pichia stipitis, verkry deur die doeltreffende induksie van die eiesoortige ADH2-promotor en die byvoeging van ‘n aminosuur-mengsel tot die gedefinieerde medium, wat die teenwoordigheid van generiese beperkinge in transkripsie, voedingstof-beskikbaarheid en biosintetiese kapasiteit van die gis vir vreemde proteïen produksie deur verskeie giste uitgewys het. Die teenwoordigheid van globale sensoriese- en beheer-meganismes is bevestig deur die fisiologiese respons van S. cerevisiae tot heteroloë proteïen produksie, wat die afwaartse regulering van biosintese en groei, en die induksie van verskeie prosesse betrokke by die algemene voedingstres-respons, ingesluit het. Heteroloë xilanase produksie is ook op ‘n na-transkripsionele vlak aktief gereguleer deur die autotrofiese transformante in reaksie tot die vlak van aminosuur beskikbaarheid. Die biosintetiese kapasiteit vir vreemde proteïen-produksie van beide rekombinante S. cerevisiae en P. stipitis is ook in reaksie tot die fisiologiese toestand van die gis en die beskikbaarheid van voedingstowwe gereguleer. Die teenwoordigheid van hierdie regulatoriese meganismes het die willekeurige manipulasie van sellulêre proteïen-biosintese bemoeilik.
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Silva, Ariosto Siqueira. "Uma abordagem de metodos computacionais para simulação de processos biologicos : simulação tridimensional e metabolica do desenvolvimento tumoral." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316889.
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Orientador: Jose Andres YunesTese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: Neste trabalho criou-se uma ferramenta de simulação e modelos computacionais para estudo da carcinogênese a fim de se responder a perguntas biológicas pertinentes ao tratamento desta doença. Os modelos computacionais se basearam no modelo teórico de Evolução Somática e Invasão Mediada por Acidez, proposto por Gatenby e Gillies, e foi implementado em uma ferramenta desenvolvida pelo autor deste trabalho no âmbito deste projeto, o Tissue Simulator (TSim, www.i-genics.com). O modelo teórico de invasão mediada por acidez propõe que células tumorais possuem maior resistência a acidez, assim como produzem quantidade de ácido lático, originado da glicólise anaeróbica, suficiente para acidificar o meio extracelular, causando assim morte do tecido saudável por apoptose induzida por acidez, e facilitando a invasão do tecido saudável pelo tumor. Estudos experimentais, na literatura, mostraram que a administração de bicarbonato de sódio na água em ratos portadores de tumores reduz o número de metástases, o que seria uma indicação de que a hipótese sobre a importância da acidez na invasividade tumoral é válida. Neste estudo, criou-se um primeiro modelo computacional para testar se o aumento da concentração de bicarbonato no sangue poderia influenciar no gradiente de acidez entre o tumor (micrometástases) e o tecido saudável, e também identificaram-se as características físico-químicas de um tampão ideal a ser usado com esse propósito. O modelo teórico de Evolução Somática, adotado neste projeto, propõe que para que um tumor epitelial se torne invasivo, é necessário que suas células adquiram três fenótipos: hiperplasia, hiperglicólise e resistência a acidez. O segundo modelo criado neste trabalho consistiu na identificação de quais seriam os valores mínimos de hiperglicólise e resistência à acidez para o aparecimento da característica de invasividade em um tumor em desenvolvimento dentro de um duto epitelial (DCIS). Uma vez identificados os fenótipos mínimos para a invasão tumoral de um DCIS, restaria saber quais as mutações em enzimas ou transportadores específicos dessa via metabólica para que o dito fenótipo seja atingido. A título de exemplo de um estudo para responder perguntas desse tipo, fez-se uma análise comparativa da robustez do fluxo glicolítico em duas células distintas: uma levedura (S. Cerevisiae) e uma célula humana especializada (célula beta pancreática), cujas enzimas principais são reguladas por estratégias distintas. Este estudo foi implementado em uma ferramenta computacional disponível na literatura (Jarnac e Matlab) e resultou na publicação de um artigo. No todo, os resultados desta tese mostram que, com o uso de ferramentas computacionais e dados quantitativos da literatura, é possível criar modelos teóricoquantitativos que podem ser usados para validar teorias sobre fenômenos biológicos assim como extrapolar novas hipóteses e testá-las, integrando-se assim a modelagem computacional no processo de pesquisa científica
Abstract: In this work, we created a piece of software and computer models for studying carcinogenesis, in order to answer biological questions related to the treatment of this disease. The computer models were inspired in the theory of Somatic Evolution and Acid Mediated Tumor Invasion, proposed by Gatenby and Gillies, and were implemented in a tool developed by the author under the scope of this thesis, Tissue Simulator (TSim, www.i-genics.com). The theory of Acid Mediated Tumor Invasion proposes that cancer cells are more resistant to toxicity of an acidic environment that they help create by producing excess of lactic acid through anaerobic glycolysis. Acidification of the extra-cellular environment causes death of healthy tissue through acid-induced apoptosis and ultimately facilitates tumor invasion. Experimental studies, from literature, showed that administration of sodium bicarbonate in water to mice bearing tumors reduced the number of metastases, thus supporting the importance of acidity in tumor invasion. In this study a computer model was built to test if an increase in concentration of bicarbonate in blood serum could alter the pH gradient between the tumor (micrometastases) and halthy tissue, as well as to identify the chemical properties of and ideal buffer with this purpose. The theory of Somatic Evolution, proposes that epithelial tumor cells are submitted to environmental barriers and are selected for three main phenotypes: hyperplasia, hyperglycolysis and acid resistance. A second computer model was created in order to identify the minimum values of these phenotypes that allowed a DCIS to change into an invasive tumor. Once the minimum phenotypic values identified, one can study how mutations on specific enzymes can alter the flux of a metabolic pathway, such as glycolysis, to produce the altered phenotype. As an example of this, we performed a comparative study of robustness of glycolytic flux in two different cells: yeast (S. cerevisiae) and pancreatic human beta-cell, whose enzymatic regulatory strategies differ. This computer model was implemented on Matlab and Jarnac. Overall, our results show that the use of computational tools and quantitative data may be used to create theoretical-quantitative models that help adressing theories about biological systems, as well as to extrapolate and tes new hypothesis, integrating the approach of computational modeling in the scientific research process
Doutorado
Genetica Animal e Evolução
Doutor em Genetica e Biologia Molecular
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Bouillaud, Dylan. "Multiscale NMR analysis of the microalgae metabolism." Thesis, Nantes, 2020. http://www.theses.fr/2020NANT4029.
Full textAbstract:
Les bio-procédés à base de microalgues sont reconnus pour des applications majeures comme la production de lipides précurseurs de biocarburant. Aujourd'hui la plupart de ces technologies vertes ne sont pas suffisamment matures en raison de coûts de production importants et sont pour cela activement développées par une importante communauté de bio-procédés. A l'interface entre la biologie et les procédés, cette communauté n'est pas familière avec la spectroscopie RMN, outil puissant d'analyse structurale et quantitative. L'objectif de cette thèse est d’évaluer le potentiel d’approches RMN multiéchelles pour le développement des bio-procédés à base de microalgues. Deux axes de recherche distincts mais complémentaires ont été développés : 1) la RMN à haut champ magnétique pour la quantification d'extraits lipidiques a montré une excellente faculté à identifier les classes lipidiques sans séparation physique de celles ci. Des séquences d'impulsions originales pour la quantification ont été évaluées, et des pistes ont qui devront être explorées ont été dégagées pour rendre l'analyse compatible en conditions de routine. Ces approches offrent une alternative pertinente aux méthodes analytiques existantes pour l'étude du métabolisme lipidique. 2) l'utilisation de la RMN de paillasse pour le suivi en ligne, non invasif et en temps réel des lipides intracellulaires dans des cultures de micro-algues, difficilement réalisable avec une autre technique d'analyse. Cette approche ouvre de nouvelles perspectives pour le contrôle et l'optimisation des bio-procédés à base de micro-alguesMicroalgae-based bioprocesses are well-known for several major applications such as production of lipids as precursors of biofuel. Nowadays, most of these green technologies are not mature enough leading to high production costs. This is the reason why they are actively developed by a substantial bioprocess community. At the interface between biology and processes, this community is not necessarily familiar with NMR spectroscopy which is a powerful structural and quantitative analytical tool. The goal of this thesis is to evaluate the potential of multi-scale NMR approaches for the development of microalgaebased bioprocesses. Two distinct but complementary research axes were developed: i) high-field NMR spectroscopy for the quantification of lipid extracts showed a great aptitude for lipid class identification without physical separation. Original pulse sequences for quantification were evaluated, opening new routes that should be further explored to become applicable in routine. These approaches offer an alternative to existing analytical methods for the study of lipid metabolism. ii) the use of benchtop NMR for the online, noninvasive and real-time monitoring of intracellular lipids in microalgae cultures which is almost impossible with other analytical techniques. This approach opens new perspectives for the optimization of microalgaebased bioprocesses
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Parker, Samuel P. "Patterns, Processes, And Scale: An Evaluation Of Ecological And Biogeochemical Functions Across An Arctic Stream Network." ScholarWorks @ UVM, 2019. https://scholarworks.uvm.edu/graddis/1036.
Full textAbstract:
Ecosystems are highly variable in space and time. Understanding how spatial and temporal scales influence the patterns and processes occurring across watersheds presents a fundamental challenge to aquatic ecologists. The goal of this research was to elucidate the importance of spatial scale on stream structure and function within the Oksrukuyik Creek, an Arctic watershed located on the North Slope of Alaska (68°36’N, 149°12’W). The studies that comprise this dissertation address issues of scale that affect our ability to assess ecosystem function, such as: methodologies used to scale ecosystem measurements, multiple interacting scales, translation between scales, and scale-dependencies.
The first methodological study examined approaches used to evaluate chlorophyll a in ethanol extracts of aquatic biofilms. Quantification of chlorophyll a is essential to the study of aquatic ecosystems, yet differences in methodology may introduce significant errors to its determination that can lead to issues of comparability between studies. A refined analytical procedure for the determination of chlorophyll a was developed under common acidification concentrations at multiple common reaction times. The refined procedure was used to develop a series of predictive equations that could be used to correct and normalize previously evaluated chlorophyll a data. The predictive equations were validated using benthic periphyton samples from northern Alaska and northwestern Vermont, U.S.A.
The second study examined interaction and translation between scales by examining how normalization approaches affect measurements of metabolism and nutrient uptake in stream sediment biofilms. The effect of particle size and heterogeneity on rates of biofilm metabolism and nutrient uptake was evaluated in colonized and native sediments normalized using two different scaling approaches. Functional rates were normalized by projected surface area and sediment surface area scaling approaches, which account for the surface area in plan view (looking top-down) and the total surface area of all sediment particles, respectively. Findings from this study indicated that rates of biogeochemical function in heterogeneous habitats were directly related to the total sediment surface area available for biofilm colonization. The significant interactions between sediment surface area and rates of respiration and nutrient uptake suggest that information about the size and distribution of sediment particles could substantially improve our ability to predict and scale measurements of important biogeochemical functions in streams.
The final study examined how stream nutrient dynamics are influenced by the presence or absence of lakes across a variety of discharge conditions and how catchment characteristics can be used to predict stream nutrients. Concentrations of dissolved organic carbon (DOC) and other inorganic nutrients were significantly greater in streams without lakes than in streams in with lakes and DOC, total dissolved nitrogen (TDN), and soluble reactive phosphorus concentrations increased as a function of discharge. Catchment characteristic models explained between 20% and 76% of the variance of the nutrients measured. Organic nutrient models were driven by antecedent precipitation and watershed vegetation cover type while inorganic nutrients were driven by antecedent precipitation, landscape characteristics and reach vegetation cover types. The developed models contribute to existing and future understanding of the changing Arctic and lend new confidence to the prediction of nutrient dynamics in streams where lakes are present.