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1
Khoshnaw, Sarbaz Hamza Abdullah. "Model reductions in biochemical reaction networks." Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/32442.
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Many complex kinetic models in the field of biochemical reactions contain a large number of species and reactions. These models often require a huge array of computational tools to analyse. Techniques of model reduction, which arise in various theoretical and practical applications in systems biology, represent key critical elements (variables and parameters) and substructures of the original system. This thesis aims to study methods of model reduction for biochemical reaction networks. It has three goals related to techniques of model reduction. The primary goal provides analytical approximate solutions of such models. In order to have this set of solutions, we propose an algorithm based on the Duhamel iterates. This algorithm is an explicit formula that can be studied in detail for wide regions of concentrations for optimization and parameter identification purposes. Another goal is to simplify high dimensional models to smaller sizes in which the dynamics of original models and reduced models should be similar. Therefore, we have developed some techniques of model reduction such as geometric singular perturbation method for slow and fast subsystems, and entropy production analysis for identifying non–important reactions. The suggested techniques can be applied to some models in systems biology including enzymatic reactions, elongation factors EF–Tu and EF–Ts signalling pathways, and nuclear receptor signalling. Calculating the value of deviation at each reduction stage helps to check that the approximation of concentrations is still within the allowable limits. The final goal is to identify critical model parameters and variables for reduced models. We study the methods of local sensitivity in order to find the critical model elements. The results are obtained in numerical simulations based on Systems Biology Toolbox (SBToolbox) and SimBiology Toolbox for Matlab. The simplified models would be accurate, robust, and easily applied by biologists for various purposes such as reproducing biological data and functions for the full models.
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Hughes, Helen Margaret. "Model systems for studying the biochemical effects of hepatotoxins." Thesis, Cardiff University, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254495.
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Wu, Zujian. "A generic approach to behaviour-driven biochemical model construction." Thesis, Brunel University, 2012. http://bura.brunel.ac.uk/handle/2438/7413.
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Modelling of biochemical systems has received considerable attention over the last decade from bioengineering, biochemistry, computer science, and mathematics. This thesis investigates the applications of computational techniques to computational systems biology, for the construction of biochemical models in terms of topology and kinetic rates. Due to the complexity of biochemical systems, it is natural to construct models representing the biochemical systems incrementally in a piecewise manner. Syntax and semantics of two patterns are defined for the instantiation of components which are extendable, reusable and fundamental building blocks for models composition. We propose and implement a set of genetic operators and composition rules to tackle issues of piecewise composing models from scratch. Quantitative Petri nets are evolved by the genetic operators, and evolutionary process of modelling are guided by the composition rules. Metaheuristic algorithms are widely applied in BioModel Engineering to support intelligent and heuristic analysis of biochemical systems in terms of structure and kinetic rates. We illustrate parameters of biochemical models based on Biochemical Systems Theory, and then the topology and kinetic rates of the models are manipulated by employing evolution strategy and simulated annealing respectively. A new hybrid modelling framework is proposed and implemented for the models construction. Two heuristic algorithms are performed on two embedded layers in the hybrid framework: an outer layer for topology mutation and an inner layer for rates optimization. Moreover, variants of the hybrid piecewise modelling framework are investigated. Regarding flexibility of these variants, various combinations of evolutionary operators, evaluation criteria and design principles can be taken into account. We examine performance of five sets of the variants on specific aspects of modelling. The comparison of variants is not to explicitly show that one variant clearly outperforms the others, but it provides an indication of considering important features for various aspects of the modelling. Because of the very heavy computational demands, the process of modelling is paralleled by employing a grid environment, GridGain. Application of the GridGain and heuristic algorithms to analyze biological processes can support modelling of biochemical systems in a computational manner, which can also benefit mathematical modelling in computer science and bioengineering. We apply our proposed modelling framework to model biochemical systems in a hybrid piecewise manner. Modelling variants of the framework are comparatively studied on specific aims of modelling. Simulation results show that our modelling framework can compose synthetic models exhibiting similar species behaviour, generate models with alternative topologies and obtain general knowledge about key modelling features.
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Wu, Jialiang. "Hybrid modeling and analysis of multiscale biochemical reaction networks." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/47723.
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This dissertation addresses the development of integrative modeling strategies capable of combining deterministic and stochastic, discrete and continuous, as well as multi-scale features. The first set of studies combines the purely deterministic modeling methodology of Biochemical Systems Theory (BST) with a hybrid approach, using Functional Petri Nets, which permits the account of discrete features or events, stochasticity, and different types of delays. The efficiency and significance of this combination is demonstrated with several examples, including generic biochemical networks with feedback controls, gene regulatory modules, and dopamine based neuronal signal transduction.
A study expanding the use of stochasticity toward systems with small numbers of molecules proposes a rather general strategy for converting a deterministic process model into a corresponding stochastic model. The strategy characterizes the mathematical connection between a stochastic framework and the deterministic analog. The deterministic framework is assumed to be a generalized mass action system and the stochastic analogue is in the format of the chemical master equation. The analysis identifies situations where internal noise affecting the system needs to be taken into account for a valid conversion from a deterministic to a stochastic model. The conversion procedure is illustrated with several representative examples, including elemental reactions, Michaelis-Menten enzyme kinetics, a genetic regulatory motif, and stochastic focusing.
The last study establishes two novel, particle-based methods to simulate biochemical diffusion-reaction systems within crowded environments. These simulation methods effectively simulate and quantify crowding effects, including reduced reaction volumes, reduced diffusion rates, and reduced accessibility between potentially reacting particles. The proposed methods account for fractal-like kinetics, where the reaction rate depends on the local concentrations of the molecules undergoing the reaction. Rooted in an agent based modeling framework, this aspect of the methods offers the capacity to address sophisticated intracellular spatial effects, such as macromolecular crowding, active transport along cytoskeleton structures, and reactions on heterogeneous surfaces, as well as in porous media.
Taken together, the work in this dissertation successfully developed theories and simulation methods which extend the deterministic, continuous framework of Biochemical Systems Theory to allow the account of delays, stochasticity, discrete features or events, and spatial effects for the modeling of biological systems, which are hybrid and multiscale by nature.
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Trumble, Troy Neal. "Early osteoarthritic changes in a canine cranial cruciate deficient model." Access citation, abstract and download form; downloadable file 15.41 Mb, 2004. http://wwwlib.umi.com/dissertations/fullcit/3131703.
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Quaiser, Tom [Verfasser]. "Data- and model-based identification of biochemical processes / Tom Quaiser." Aachen : Shaker, 2012. http://d-nb.info/1069045845/34.
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Gibb, Jason Ocean Telford. "NMR studies on the effects of model pollutants in selected invertebrate species." Thesis, Birkbeck (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268053.
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Banks, Christopher Jon. "Spatio-temporal logic for the analysis of biochemical models." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/10512.
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Process algebra, formal specification, and model checking are all well studied techniques in the analysis of concurrent computer systems. More recently these techniques have been applied to the analysis of biochemical systems which, at an abstract level, have similar patterns of behaviour to concurrent processes. Process algebraic models and temporal logic specifications, along with their associated model-checking techniques, have been used to analyse biochemical systems. In this thesis we develop a spatio-temporal logic, the Logic of Behaviour in Context (LBC), for the analysis of biochemical models. That is, we define and study the application of a formal specification language which not only expresses temporal properties of biochemical models, but expresses spatial or contextual properties as well. The logic can be used to express, or specify, the behaviour of a model when it is placed into the context of another model. We also explore the types of properties which can be expressed in LBC, various algorithms for model checking LBC - each an improvement on the last, the implementation of the computational tools to support model checking LBC, and a case study on the analysis of models of post-translational biochemical oscillators using LBC. We show that a number of interesting and useful properties can be expressed in LBC and that it is possible to express highly useful properties of real models in the biochemistry domain, with practical application. Statements in LBC can be thought of as expressing computational experiments which can be performed automatically by means of the model checker. Indeed, many of these computational experiments can be higher-order meaning that one succinct and precise specification in LBC can represent a number of experiments which can be automatically executed by the model checker.
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Reid, Cherith Norma. "Biochemical basis of interspecific cell signalling : an invertebrate and vertebrate model." Thesis, Queen's University Belfast, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326448.
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Mintz, Christina. "Predicting Chemical and Biochemical Properties Using the Abraham General Solvation Model." Thesis, University of North Texas, 2009. https://digital.library.unt.edu/ark:/67531/metadc28373/.
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Several studies were done to illustrate the versatillity of the Abraham model in mathematically describing the various solute-solvent interactions found in a wide range of different chemical and biological systems. The first study focused on using the solvation model to construct mathematical correlations describing the minimum inhibitory concentration of organic compounds for growth inhibition towards the three bacterial strains Porphyromonas gingivalis, Selenomonas artemidis, and Streptococcus sobrinus. The next several studies expand the practicallity of the Abraham model by predicting free energies of partition in chemical systems. The free energy studies expand the use of the Abraham model to other temperatures and properties by developing correlations for the enthalpies of solvation of gaseous solutes of various compounds dissolved in water, 1-octanol, hexane, heptane, hexadecane, cyclohexane, benzene, toluene, carbon tetrachloride, chloroform, methanol, ethanol, 1-butanol, propylene carbonate, dimethyl sulfoxide, 1,2-dichloroethane, N,N-dimethylformamide, tert-butanol, dibutyl ether, ethyl acetate, acetonitrile, and acetone. Also, a generic equation for linear alkanes is created for use when individual datasets are small. The prediction of enthalpies of solvation is furthered by modifying the Abraham model so that experimental data measured at different temperatures can be included into a single correlation expression. The temperature dependence is directly included in the model by separating each coefficient into an enthalpic and entropic component. Specifically, the final study describes the effects of temperature on the sorption coefficients of organic gases onto humic acid. The derived predicted values for each research study show a good correlation with experimental values.
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Leising, Sophie. "Nonlinear controller synthesis for complex chemical and biochemical reaction systems." Link to electronic thesis, 2005. http://www.wpi.edu/Pubs/ETD/Available/etd-050205-152657/.
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Thesis (M.S.) -- Worcester Polytechnic Institute.Keywords: model predictive control; discrete-time model; continuous-time model; nonlinear systems; Lyapunov design. Includes bibliographical references (p. 99-102).
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Chen, Minghan. "Stochastic Modeling and Simulation of Multiscale Biochemical Systems." Diss., Virginia Tech, 2019. http://hdl.handle.net/10919/90898.
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Numerous challenges arise in modeling and simulation as biochemical networks are discovered with increasing complexities and unknown mechanisms. With the improvement in experimental techniques, biologists are able to quantify genes and proteins and their dynamics in a single cell, which calls for quantitative stochastic models for gene and protein networks at cellular levels that match well with the data and account for cellular noise.
This dissertation studies a stochastic spatiotemporal model of the Caulobacter crescentus cell cycle. A two-dimensional model based on a Turing mechanism is investigated to illustrate the bipolar localization of the protein PopZ. However, stochastic simulations are often impeded by expensive computational cost for large and complex biochemical networks. The hybrid stochastic simulation algorithm is a combination of differential equations for traditional deterministic models and Gillespie's algorithm (SSA) for stochastic models. The hybrid method can significantly improve the efficiency of stochastic simulations for biochemical networks with multiscale features, which contain both species populations and reaction rates with widely varying magnitude. The populations of some reactant species might be driven negative if they are involved in both deterministic and stochastic systems. This dissertation investigates the negativity problem of the hybrid method, proposes several remedies, and tests them with several models including a realistic biological system.
As a key factor that affects the quality of biological models, parameter estimation in stochastic models is challenging because the amount of empirical data must be large enough to obtain statistically valid parameter estimates. To optimize system parameters, a quasi-Newton algorithm for stochastic optimization (QNSTOP) was studied and applied to a stochastic budding yeast cell cycle model by matching multivariate probability distributions between simulated results and empirical data. Furthermore, to reduce model complexity, this dissertation simplifies the fundamental cooperative binding mechanism by a stochastic Hill equation model with optimized system parameters. Considering that many parameter vectors generate similar system dynamics and results, this dissertation proposes a general α-β-γ rule to return an acceptable parameter region of the stochastic Hill equation based on QNSTOP. Different objective functions are explored targeting different features of the empirical data.Doctor of Philosophy
Modeling and simulation of biochemical networks faces numerous challenges as biochemical networks are discovered with increased complexity and unknown mechanisms. With improvement in experimental techniques, biologists are able to quantify genes and proteins and their dynamics in a single cell, which calls for quantitative stochastic models, or numerical models based on probability distributions, for gene and protein networks at cellular levels that match well with the data and account for randomness. This dissertation studies a stochastic model in space and time of a bacterium’s life cycle— Caulobacter. A two-dimensional model based on a natural pattern mechanism is investigated to illustrate the changes in space and time of a key protein population. However, stochastic simulations are often complicated by the expensive computational cost for large and sophisticated biochemical networks. The hybrid stochastic simulation algorithm is a combination of traditional deterministic models, or analytical models with a single output for a given input, and stochastic models. The hybrid method can significantly improve the efficiency of stochastic simulations for biochemical networks that contain both species populations and reaction rates with widely varying magnitude. The populations of some species may become negative in the simulation under some circumstances. This dissertation investigates negative population estimates from the hybrid method, proposes several remedies, and tests them with several cases including a realistic biological system. As a key factor that affects the quality of biological models, parameter estimation in stochastic models is challenging because the amount of observed data must be large enough to obtain valid results. To optimize system parameters, the quasi-Newton algorithm for stochastic optimization (QNSTOP) was studied and applied to a stochastic (budding) yeast life cycle model by matching different distributions between simulated results and observed data. Furthermore, to reduce model complexity, this dissertation simplifies the fundamental molecular binding mechanism by the stochastic Hill equation model with optimized system parameters. Considering that many parameter vectors generate similar system dynamics and results, this dissertation proposes a general α-β-γ rule to return an acceptable parameter region of the stochastic Hill equation based on QNSTOP. Different optimization strategies are explored targeting different features of the observed data.
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Ngai, H. Y. Heidi. "Proteomics analysis of potential biomarkers and pathogenic mechanisms of membranous nephropathy in a rat model of passive Heymann nephritis." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B38827372.
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Pu, Yang. "The Art of Modeling and Simulation of Multiscale Biochemical Systems." Diss., Virginia Tech, 2015. http://hdl.handle.net/10919/52347.
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In this thesis we study modeling and simulation approaches for multiscale biochemical systems. The thesis addresses both modeling methods and simulation strategies. In the first part, we propose modeling methods to study the behavior of the insulin secretion pathway. We first expand the single cell model proposed by Bertram et. al. to model multiple cells. Synchronization among multiple cells is observed. Then an unhealthy cell model is proposed to study the insulin secretion failure caused by weakening of mitochondria function. By studying the interaction between the healthy and unhealthy cells, we find that the insulin secretion can be reinstated by increasing the glucokinase level. This new discovery sheds light on antidiabetic medication. In order to study the stochastic dynamics of the insulin secretion pathway, we first apply the hybrid method to model the discrete events in the insulin secretion pathway. Based on the hybrid model, a probability based measurement is proposed and applied to test the new antidiabetic remedy. In the second part, we focus on different simulation schemes for multiscale biochemical systems. We first propose a partitioning strategy for the hybrid method which leads to an efficient way of building stochastic cell cycle models. Then different implementation methods for the hybrid method are studied. A root finding method based on inverse interpolation is introduced to implement the hybrid method with three different ODE solvers. A detailed discussion of the performance of these three ODE solvers is presented. Last, we propose a new strategy to automatically detect stiffness and identify species that cause stiffness for the Tau-Leaping method, as well as two stiffness reduction methods. The efficiency is demonstrated by applying this new strategy on a stiff decaying dimerization model and a heat shock protein regulation model.Ph. D.
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Naswa, Sudhir. "Representation of Biochemical Pathway Models : Issues relating conversion of model representation from SBML to a commercial tool." Thesis, University of Skövde, School of Humanities and Informatics, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-28.
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Background: Computational simulation of complex biological networks lies at the heart of systems biology since it can confirm the conclusions drawn by experimental studies of biological networks and guide researchers to produce fresh hypotheses for further experimental validation. Since this iterative process helps in development of more realistic system models a variety of computational tools have been developed. In the absence of a common format for representation of models these tools were developed in different formats. As a result these tools became unable to exchange models amongst them, leading to development of SBML, a standard exchange format for computational models of biochemical networks. Here the formats of SBML and one of the commercial tools of systems biology are being compared to study the issues which may arise during conversion between their respective formats. A tool StoP has been developed to convert the format of SBML to the format of the selected tool.
Results: The basic format of SBML representation which is in the form of listings of various elements of a biochemical reaction system differs from the representation of the selected tool which is location oriented. In spite of this difference the various components of biochemical pathways including multiple compartments, global parameters, reactants, products, modifiers, reactions, kinetic formulas and reaction parameters could be converted from the SBML representation to the representation of the selected tool. The MathML representation of the kinetic formula in an SBML model can be converted to the string format of the selected tool. Some features of the SBML are not present in the selected tool. Similarly, the ability of the selected tool to declare parameters for locations, which are global to those locations and their children, is not present in the SBML.
Conclusions: Differences in representations of pathway models may include differences in terminologies, basic architecture, differences in capabilities of software’s, and adoption of different standards for similar things. But the overall similarity of domain of pathway models enables us to interconvert these representations. The selected tool should develop support for unit definitions, events and rules. Development of facility for parameter declaration at compartment level by SBML and facility for function declaration by the selected tool is recommended.
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Hughes, Alistair Paul. "The accuracy of linear flux models in predicting reaction rate profiles in a model biochemical reaction system." Master's thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/9116.
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Includes bibliographical referencesMetabolic flux analysis is commonly used in the modelling of biochemical reactions. The use of MFA models has gained large amounts of interest due to the simplicity of the computational procedures required for the model, and the exclusion of difficult to measure intracellular reaction data. There are many examples of the use of MFA models in literature studies in a number of applications, ranging from the medical industry through to the development of novel biochemical processes. Little to no mention is provided in literature studies regarding the applicability of the MFA model to a specified set of reaction data. Furthermore, the techniques and routines used to compute the flux models are not well described in these studies. The objectives of this research were to determine the sensitivity of the MFA models to various operating and kinetic parameters and to highlight the considerations required when setting up the computational routine used to solve the flux balances. The study was conducted using a model pathway populated with a set of hypothetical elemental reactions and branch points. The model pathway was used in this study to negate the affects of complex regulatory biochemical architectures which are not well described in literature. The use of the model pathway ensured that the reaction system was thermodynamically feasible and there was consistency in the mass balances. The exclusion of the complex regulatory reactions did not affect the accuracy of the results generated in this study. A set of reaction mechanisms were used to describe each reaction step and were populated with parameters reference from literature. The cellular and reactor mass balances were generated using correlations presented in literature.
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Kunsevi-Kilola, Carine. "The effect of Rooibos on trace elements absorption and biochemical parameters-Amurine model." Thesis, Cape Peninsula University of Technology, 2014. http://hdl.handle.net/20.500.11838/1463.
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Thesis submitted in fulfillment of the requirements for the degree
Master Technologiae: Biomedical Technology
In the
Faculty of Health and Wellness Sciences
At the
CAPE PENINSULA UNIVERSITY OF TECHNOLOGY
2014Over the past few decades, it has been shown that various critical diseases including heart disease, cancer, and diabetes associated with free radical generation and low endogenous antioxidant capacity, lead to oxidative stress and cell injury. In recent years, numerous studies have also reported that antioxidants, present in various beverages, vegetables and some foods have attracted a significant research interest due to their potential benefits to human health. However, epidemiological evidence shows a correlation between the intake of food rich in antioxidants and the reduced incidence of some mortality of chronic diseases, certain cancers and coronary heart disease. The aims of this study were to determine the effects of rooibos teas (fermented and unfermented) and green tea as a comparison on the biochemical parameters and the trace element absorption in a rat model. In this study 4 groups of experimental animals were used. All groups had ad libitum access to standard rat chow. Group A, the controls (11 animals), were fed with tap water; group B (11 animals) were fed with the liquid extract of fermented rooibos tea; group C (9 animals) were fed with the liquid extracts of unfermented rooibos and group D (9 animals) were fed with the liquid extract of green tea. All groups were fed for a period of 10 weeks. After the feeding period, the animals were sacrificed by euthanization with intraperitoneal injections of pentobarbital. Blood was sampled by cardiac puncture and centrifuged to obtain the serum. Some elemental analyses were performed with X-ray emission and backscattering. ICP-OES was used to determine the magnesium content. For X-ray emission, backscattering and ICP-OES analyses, 100 μL of each serum sample in a group were added to 2 mL freeze-drying tube. Of the combined specimen, 100 μL was used for the magnesium determination by ICP-OES. The remainder of the combined serum specimens for each group were freeze-dried at -80 ºC and then pressed into a pellet. The pellet was coated with carbon and analyzed using X-ray emission and backscattering. The elemental X-rays of P, S, Ca, Mn, Fe, Cu, Co, Zn, Mo, Ca and Se emitted were quantified to obtain the respective concentrations. Biochemical chemistry analyses were performed on each serum sample of each animal. The biochemical parameters tested for were total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, blood urea nitrogen, uric acid, total cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and creatinine. The P concentration increased (p=0.028) when fed with the fermented rooibos tea liquid extract and S content increased when fed with the - the unfermented tea liquid extract (p=0.041). The concentrations of Cl and Cr were not affected (p>0.05) by any of tea liquid extracts. The unfermented rooibos tea liquid extract and the green tea indicated a decrease in the concentrations of Fe (p=0.031 and p=0.032, respectively) and Mn (p=0.041 and p=0.034, respectively). The concentrations of Fe, Zn and Cu in the serum increased when feeding with fermented rooibos tea liquid extract (p=0.024; p=0.030 and p=0.015, respectively) while Se, Mo and Mg concentrations were decreased by the liquid extracts of the fermented, unfermented and green teas (p=0.014, p=0.017 and p=0.011; p=0.024, p=0.026 and p=0.019; p=0.031, p=0.034 and p=0.025, respectively). Concerning the biochemical parameters, the total protein, globulin and the uric acid contents in the serum sample were slightly affected with the green tea extract (p=0.041, p=0.039 and p=0.047 respectively). The albumin, lactate dehydrogenase, blood urea nitrogen, the total cholesterol, the alanine aminotransferase and the aspartate aminotransferase concentrations were not affected (p>0) by any of the tea liquid extracts. However, the total bilirubin content was decreased (p=0.012) when feeding with the fermented rooibos group while the creatine phosphokinase and the creatinine contents were decreased (p=0.042 and p=0.033, respectively) when feeding with the unfermented rooibos tea liquid extract.
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Daruwalla, Anahita. "Understanding Carotenoid and Retinoid Biochemical Diversity using Novel Archaeal and Eukaryotic Model Systems." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1626709424672807.
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Ngai, H. Y. Heidi, and 魏凱怡. "Proteomics analysis of potential biomarkers and pathogenic mechanisms of membranous nephropathy in a rat model of passive Heymann nephritis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38827372.
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Kunsevi-Kilola, Carine. "The effect of Rooibos on trace elements absorption and biochemical parameters : a murine model." Thesis, Cape Peninsula University of Technology, 2014. http://hdl.handle.net/20.500.11838/2248.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2014.Over the past few decades, it has been shown that various critical diseases including heart disease, cancer, and diabetes associated with free radical generation and low endogenous antioxidant capacity, lead to oxidative stress and cell injury. In recent years, numerous studies have also reported that antioxidants, present in various beverages, vegetables and some foods have attracted a significant research interest due to their potential benefits to human health. However, epidemiological evidence shows a correlation between the intake of food rich in antioxidants and the reduced incidence of some mortality of chronic diseases, certain cancers and coronary heart disease. The aims of this study were to determine the effects of rooibos teas (fermented and unfermented) and green tea as a comparison on the biochemical parameters and the trace element absorption in a rat model. In this study 4 groups of experimental animals were used. All groups had ad libitum access to standard rat chow. Group A, the controls (11 animals), were fed with tap water; group B (11 animals) were fed with the liquid extract of fermented rooibos tea; group C (9 animals) were fed with the liquid extracts of unfermented rooibos and group 0 (9 animals) were fed with the liquid extract of green tea. All groups were fed for a period of 10 weeks. After the feeding period, the animals were sacrificed by euthanization with intraperitoneal injections of pentobarbital. Blood was sampled by cardiac puncture and centrifuged to obtain the serum. Some elemental analyses were performed with X-ray emission and backscattering. ICP-OES was used to determine the magnesium content. For X-ray emission, backscattering and ICP-OES analyses, 100 µL of each serum sample in a group were added to 2 ml freeze-drying tube. Of the combined specimen, 100 µL was used for the magnesium determination by ICP-OES. The remainder of the combined serum specimens for each group were freeze-dried at -80°C and then pressed into a pellet. The pellet was coated with carbon and analyzed using X-ray emission and backscattering. The elemental X-rays of P, S, Ca, Mn, Fe, Cu, Co, Zn, Mo, Ca and Se emitted were quantified to obtain the respective concentrations. Biochemical chemistry analyses were performed on each serum sample of each animal. The biochemical parameters tested for were total protein, albumin, globulin, total bilirubin, lactate dehydrogenase, blood urea nitrogen, uric acid, total cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase and creatinine.
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Jakovljevic, Ivona [Verfasser], Friedemann [Akademischer Betreuer] Kaiser, and Barbara [Akademischer Betreuer] Drossel. "Model for spatiotemporal organization of biochemical circadian clocks / Ivona Jakovljevic. Betreuer: Friedemann Kaiser ; Barbara Drossel." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2011. http://d-nb.info/1105562344/34.
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Chen, Zhoutao 1972. "A mouse model for methylenetetrahydrofolate reductase deficiency and biochemical studies of the recombinant human enzyme /." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37878.
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Hyperhomocysteinemia is a risk factor for cardiovascular disease and stroke. Nutritional and/or genetic disruptions in homocysteine metabolism can cause hyperhomocysteinemia. Mild methylenetetrahydrofolate reductase (MTHFR) deficiency due to the 677C → T mutation in the MTHFR gene is the most common genetic cause of hyperhomocysteinemia. The 677C → T variant is associated with an increased risk for neural tube defects, pregnancy complications, schizophrenia and Down syndrome, and with a decreased risk for colon cancer and leukemia. This variant is also a potential risk factor for vascular disease. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. We have generated mice with a knockout of the Mthfr gene. The Mthfr-deficient mice exhibit hyperhomocysteinemia and decreased methylation capacity. The Mthfr+/- mice appear normal, whereas the Mthfr-/- mice are smaller and have reduced survival. Abnormal external granule neuron development associated with increased cell death in the cerebellum was observed in the Mthfr-/- mice.Evidence for cardiovascular pathology was obtained in several ways. Impaired aortic relaxation response to acetylcholine was seen in the Mthfr +/- mice fed a high methionine diet. Both Mthfr+/- and Mthfr-/- mice fed a low folate high methionine diet developed myocardial fibrosis in the left ventricle. Abnormal lipid deposition in the proximal portion of the aorta was observed in older Mthfr+/- and Mthfr-/- mice. After crossing Mthfr -deficient mice with apoE-null mice, we demonstrated that MTHFR deficiency promoted atherogenesis and its progression in the apoE-null mice.
Gene expression in brain of Mthfr-deficient mice was investigated via microarray analysis. Five genes with altered expression in the brain of Mthfr-/- mouse were validated by RT-PCR. In biochemical studies of human MTHFR, both FAD and folate were shown to stabilize the purified recombinant wild type and mutant MTHFRs from the baculovirus expression system against heat inactivation. The effect of folate appeared to be secondary to that of FAD, and S-adenosylmethionine (SAM) inhibited purified wild type and mutant MTHFRs with similar efficiency.
This dissertation will significantly contribute to our understanding of the role of MTHFR in human disease.
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Paik, Jisun. "CIS-retinol dehydrogenase : characterization and biochemical analysis of 9-cis-retinol metabolism in two model systems /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/6600.
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Martín, Sómer Ana. "Gas-phase reactivity of Lewis adducts and model biochemical systems : quantum chemistry and molecular dynamics perspectives." Thesis, Evry-Val d'Essonne, 2014. http://www.theses.fr/2014EVRY0057/document.
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La réactivité à la phase gazeuse, ou réactivité intrinsèque, a une grande importance puisque l’absence d’interactions avec un solvant peut donner lieu à une réactivité très diffèrent donc, nous permettant d’avoir une meilleure connaissance des propriétés moléculaires. Avec l’émergence en 1900 de nouvelles techniques expérimentales, plus précisément des techniques pour ioniser plus doucement, la chimie des ions en phase gazeuse s’est développée significativement et a supposé en changement dans l’idée de la réactivité chimique. Cet manuscrit est divisé en deux parties chacune d’elles concernant un aspect diffèrent de la réactivité en phase gazeuse.La premier partie, Part I, étude l’acidité intrinsèque d’une série de bases de Lewis du groupe 15 du tableau périodique, l’accent étant mis sur le changements d’acidité ayant lieue après la formation du complexe de Lewis. Divers acides de Lewis appartenant ou groupe 13 on été tenus en compte. Afin d’expliquer l’origine de l’augment d’acidité observé plusieurs méthodes théoriques on été employés. Pour le calcul de l’acidité intrinsèque ont a employé la théorie de la fonctionnelle de la densité (DFT, sigle pour Density Functional Theory) et des méthodes qui sont basées à la fonction d’onde. Pour décrire les variations dans la configuration électronique ayant lieu à la formation du complexe (et qui sont les responsables du changement d’acidité susmentionné) nous avons utilisé des méthodes complémentaires pour l’analyse de la population électronique (AIM, ELF et NBO). Il est important de souligner qu’une partie des résultats présentés dans cet manuscrit on été déjà corroborés par les résultats expérimentaux.La deuxième partie, Part II, est centrée sur l’étude de la réactivité unimoléculaire des ions formamide-M2+ (M = Ca, Sr). Dans ce cas particulier, les ions choisis avaient été déjà étudiés expérimentalement avec la technique de dissociation induite par collision (CID, sigle pour Collision Induced Dissociation). Tout au long de cette deuxième partie, nous avons étudié et caractérisé les différents mécanismes de fragmentation des deux ions, en utilisant diffèrent méthodes théoriques qui sont complémentaires entre eux. Premièrement, ont a évalué divers fonctionnelles afin de trouver le plus approprié pour maintenir le coût computationnelle bas au même temps que d’obtenir des résultats fiables. Ensuite, on a modélisé par moyen de simulations de dynamique la réactivité aux temps courts (< 2.5 femto seconds). En outre, en se servant des données obtenues antérieurement, on a étudié la cinétique de fragmentation avec la théorie statistique RRKM, pour les réactions «lents » (t > 2.5 fs). L’utilisation de cette procédure multi-échelle nous permet de rationaliser l’origine de tous les produits observés expérimentalement ainsi que de donner une explication aux différences entre les deux ions considérés. Pour finir, dans le quatrième chapitre sont énumérés et décrits brièvement les différents méthodes employés au cours de cet travail, tant théorétiques que expérimentauxThe so-called intrinsic reactivity (gas-phase reactivity) is of great importance since the absence of interaction with a solvent can result in very different reactivity patterns, allowing for a better understanding of molecular properties. With the advent in the 1900s of new experimental techniques, notably soft ionization methods such as electrospray ionization, the gas-phase ion chemistry has significantly developed in the last decades of the 1900s with a concomitant change in our view of chemical reactivity. The present manuscript is divided in two different parts, each one dealing with different aspects of gas-phase reactivity.Part I is concerned with the study of the intrinsic acidity of a series of group 15 Lewis bases. The changes on the aforementioned intrinsic acidity as the Lewis bases form adducts with group 13 Lewis acids is the main subject of this part. Thus, the origin for the acidity enhancement observed upon adduct formation is rationalized by means of different theoretical methods. High-level DFT and ab initio calculation were performed in order to compute theoretical acidities of the molecules under survey. Complementary to this, population analysis techniques such as AIM, ELF, and NBO were used to analyze the changes on the electronic configurations of those molecules and therefore provide with an explanation to the observed acidities. It is worth to stress the fact that part of the results were as well confirmed by means of experimental measurements. Part II focuses in unimolecular reactivity of molecular ions, namely, formamide-M2+ (M = Ca, Sr). In this case, experiments studying the Collision Induced Reactivity (CID) of these ions were already performed and through the second part of this manuscript the fragmentation mechanism of both ions are studied and characterized using different, but complementary, theoretical techniques. It is worth to mention that in a very first-step, an assessment of different methods to perform reliable electronic structure calculations while maintaining the lower possible computational cost. In the one hand, a kinetic study of the fragmentation process using the statistical theory RRKM, to describe the long-time reactivity (> fs). On the other hand, direct dynamics simulations are performed in order to describe the short-time (< 2.5 fs) non-statistical reactivity. This multi-scale approach allowed us to account for all the products observed in the CID experimental spectra of formamide-M2+ ( M = Ca, Sr), as well as the differences between them. In the fourth chapter a summary of the experimental and theoretical procedures used to perform the work presented in this manuscript is provided
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Sapotnick, Alexander [Verfasser]. "On a finite element approach for the solution of a mechanically stimulated biochemical fracture healing model / Alexander Sapotnick." Hannover : Technische Informationsbibliothek (TIB), 2015. http://d-nb.info/1129628175/34.
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Sáez, Avaria Claudio. "Physiological, biochemical, and molecular responses to copper stress in different strains of the model brown alga Ectocarpus siliculosus." Thesis, University of Plymouth, 2014. http://hdl.handle.net/10026.1/3008.
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Brown algae have been the focus of metal ecotoxicology research for over 60 years, mainly because of their high metal accumulation capacity and reputed resistance. Now that Ectocarpus siliculosus has been positioned as a model for the study of brown algae, and that the genome has been recently sequenced and annotated, new lines of research have been made possible on these ecologically and economically important organisms, including the field of ecotoxicology. Several strains of E. siliculosus have been collected and isolated from locations around the world, thus providing the opportunity to study inter-population differences in their responses to environmental stress. This investigation can be split into three main sections. In the first part Cu exposure experiments were carried out under laboratory conditions using three strains of E. siliculosus: Es524 from a Cu polluted location in Chile, REP10-11 from a metal polluted (including Cu) location in England and LIA4A from a pristine site in Scotland. Strains were exposed for 10 d to concentrations ranging between 0 and 2.4 μM Cu. We measured different parameters: relative growth rates; metal accumulation (extracellular and intracellular); phytochelatins and the expression of related enzymes; oxidative stress responses as manifested in lipid peroxidation and levels of H2O2, and levels of pigments; levels of antioxidants glutathione and ascorbate (in reduced and oxidised forms), and phenolic compounds; and the activity of the antioxidant enzymes superoxide dismutase, catalase, and ascorbate peroxidise. Strain Es524 was the most efficient in counteracting the effects of Cu stress as manifested by a combination of Cu exclusion production of metal chelators, upregulation of oxidative enzymes, and strong antioxidant metabolism. REP10-11 also showed effective Cu defences, especially related to glutathione-ascorbate interactions. LIA4A was the least tolerant strain, with metabolic defences significantly less effective against Cu exposure. In part two a novel transplantation experiment was developed to compare responses in the field with those obtained in the laboratory. The study was carried out at a metal polluted and a low-impacted site in central Chile using strain Es524 (as in the laboratory experiments) and Es147, isolated from a low metal-polluted site in Chile. From the biomass, we conducted similar measurements of Reactive Oxygen Metabolism (ROM) as for the laboratory experiments described in the first part. In agreement with the laboratory experiments, strain Es524 displayed a higher resistance to metal stress. Because they behaved similarly between strains, the best suggested biomarker candidates for future assessments are metal accumulation, glutathione and ascorbate in reduced and oxidised forms, phenolic compounds, and the activity of superoxide dismutase. The method is simple, widely applicable in temperate environments, cost-effective, and provides a reliable representation of metal bioavailability in the environment. In the final part of the study a novel technique for the co-extraction of RNA and DNA, using a high pH Tris-HCl buffer, from small amounts of biomass of different strains of E. siliculosus was successfully developed. The extraction of nucleic acids from brown algae is considered to be difficult and the product is of poor quality due to the high concentrations of interfering secondary metabolites such as phenolics and polysaccharides. The protocol devised here provided high yields of pure RNA and DNA that are suitable for molecular analyses. This investigation provides new insights on metal stress metabolism in brown algae, and demonstrates that metal resistance is dependent on inherited defences developed over a long history of exposure. Furthermore, the good agreement between the results obtained in the laboratory with those from the field study confirms that the responses expressed under controlled laboratory conditions are representative of stress metabolism of E. siliculosus under natural conditions.
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Zhou, Shanshan. "QUARTZ CRYSTAL MICROBALANCE INVESTIGATION OF CELLULOSOME ACTIVITY FROM CLOSTRIDIUM THERMOCELLUM ON MODEL CELLULOSE FILMS." UKnowledge, 2014. http://uknowledge.uky.edu/cme_etds/31.
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The cost of deconstructing cellulose into soluble sugars is a key impediment to the commercial production of lignocellulosic biofuels. The use of the quartz crystal microbalance (QCM) to investigate reaction variables critical to enzymatic cellulose hydrolysis is investigated here, extending previous studies of fungal cellulase activity for the first time to whole cell cellulases. Specifically, the activity of the cellulases of Clostridium thermocellum, which are in the form of cellulosomes, was investigated. To clearly differentiate the activity of free cellulosome and cell-bound cellulosome, the distribution of free cellulosome and cell-bound cellulosome in crude cell broth at different growth stages of C. thermocellum (ATCC 27405) was quantified. Throughout growth, greater than 70% of the cellulosome in the crude cell broth was unattached to the cell. The frequency response of the QCM was shown to capture adsorption and hydrolysis of amorphous cellulose films by the whole-cell cellulases. Further, both crude cell broth and free cellulosomes were found to have similar inhibition pattern (within 0 - 10 g/L cellobiose). Thus, kinetic models developed for the cell-free cellulosomes, which allow for more accurate interfacial adsorption analysis by QCM than their cell-attached counterparts, may provide insight into hydrolysis events in both systems.
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Alinde, Olatogni Berenice Lidwine. "Effects of red palm oil-supplementation on oxidative stress biomarkers in an experimental rat model." Thesis, Cape Peninsula University of Technology, 2012. http://hdl.handle.net/20.500.11838/2257.
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Thesis (MTech (Biomedical Technology))--Cape Peninsula University of Technology, 2012.Oxidative stress, in recent times appears to be a major underlying risk factor in the occurrence of various diseases such as cardiovascular disease (CVD) and ischemic heart disease (IHD). During oxidative stress, there is an imbalance between the production of reactive oxygen species (ROS) and antioxidant defence mechanisms in favour of ROS. This results in severe cellular damages in the heart, vascular membranes and other organs. Potential benefits of dietary supplements as one of the major quenching elements against oxidative stress have been highlighted. Thus, a growing interest has been stimulated in finding natural alternatives for the treatment and! or prevention of oxidative stress-mediated diseases. Red palm oil (RPO), refined from the tropical plant Elaeis guineensis was used in this study since it has captivated much attention in the health sector lately. The effects of RPO-supplementation on oxidative stress biomarkers as well as homocysteine, a cardiovascular disease risk factor in an oxidative stress-induced rat model were investigated in this in vivo study. All experiments were conducted for a period of six weeks. Male Wistar rats (120-150g) were randomly divided into six groups (n=5) where all the rats received a standard diet. Two groups (groups C, D) were supplemented with 0.175g RPO (7g RPO/kg chow) for four weeks whereas groups (groups E, F) were given 0.175g RPO (7g RPO/kg chow) supplementation for six weeks. Rats in control groups (groups A, B) were not given any RPO-supplementation. Groups B, 0, F were induced with oxidative stress by injection of 0.5ml (20IlM/100g of body weight) organic tertiary-butyl hydroperoxide. All parameters were determined using appropriate methods in plasma, serum and erythrocytes. Data were expressed as mean ± SEM. No significant differences were obtained between groups for total antioxidant capacity and glutathione peroxidase activity. Red palm oil supplementation significantly increased superoxide dismutase activity after 6 weeks consumption, total glutathione levels after 4 weeks consumption and homocysteine levels after four and six weeks consumption in rats not subjected to oxidative stress. Under oxidative stress conditions, malondialdehyde (MOA) level, a marker of oxidative stress related damage, significantly increased in rats receiving a standard diet. However, when RPO diet was supplemented for 4 and 6 weeks, MOA levels significantly decreased towards the value of normal controls. In conclusion, our findings suggest that RPO-supplementation could ameliorate antioxidant status in the body through its potential ability to increase some antioxidant enzymes activity. Similarly, it is suggested that RPO-supplementation could protect the rat against oxidative stress induced damage in diseased state.
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Moore, Leah Kathryn. "Neuronal viability and biochemical alterations after mechanical stretch injury: ban in vitro model of traumatic brain injury-induced neourodegeneration." Thesis, Georgia Institute of Technology, 2003. http://hdl.handle.net/1853/5362.
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Niu, Zhuolu [Verfasser], and Martin [Akademischer Betreuer] Biel. "Biochemical and functional analysis of a genetic mouse model with altered HCN channel expression / Zhuolu Niu ; Betreuer: Martin Biel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/113104052X/34.
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Hurter, Etienne. "Biochemical and physiological changes associated with estrogenic activity in Xenopus laevis : a model for the detection of endocrine disruption." Thesis, Stellenbosch : Stellenbosch University, 2003. http://hdl.handle.net/10019.1/53309.
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Dissertation (PhD)--University of Stellenbosch, 2003.ENGLISH ABSTRACT: Concern has increased that widespread adverse effects are occurring in humans and wildlife populations as a result of exposure to environmental chemicals (mostly man-made) that disrupt the normal functioning of the endocrine system. Many pharmaceutical, agricultural and industrial chemicals, acting as endocrine modulating compounds (EDCs), have been detected in an accumulated form in food, in drinking water and in the environment. Although the levels of these chemicals can be measured analytically, it is important to evaluate biological activity. For this, animal models are used and relevant bioassays developed. These assays are based on biological markers, which are specific xenobiotically-induced physiological responses and are usually deviations in cellular or biochemical components, processes or structures. Vitellogenin is a large protein complex, produced in the liver under estrogen control and circulates in the plasma, destined for incorporation into the developing oocyte in female oviparous vertebrates. Since vitellogenin production is low or nonexistent in males, its presence may therefore be interpreted as evidence of exposure to estrogenic environmental contaminants. In this study the African Clawed Frog, Xenopus laevis was used as model to study the effects of estrogens on biochemical and physiological parameters associated with vitellogenesis. As a starting point the seasonal female reproductive cycle in a natural Xenopus laevis population in terms of ovarian state, plasma vitellogenin and plasma estrogen levels was studied. It was shown that plasma vitellogenin and estrogen levels were seasonal and correlated to a seasonal ovarian cycle, which peaked during spring. However, although seasonality existed, there were reproductively active individuals at any time during the year. Increases in plasma estrogen levels predated increases in plasma vitellogenin levels and ovarian maturation. Lipoprotein profiles, as well as plasma cholesterol, triglyceride and phospholipid concentrations were determined and it was shown that estrogen affected these in such a way that these parameters could be used as additional markers in estrogen contamination studies. In order to develop an in vitro bioassay to screen for estrogenic activity, the use of hepatic tissue cultures was investigated. Optimal culture conditions were established and increased sensitivity in the estrogenic response was obtained by using liver slices from male frogs that were pre-treated with estrogen. Validation studies proved that this bioassay could be employed for routine screening of water and chemical samples. In order to refine the Xenopus laevis vitellogenin ELISA and liver slice bioassay, existing polyclonal anti-vitellogenin antibodies were replaced by culturing monoclonal antibodies. Selected antibodies were characterised and ELISAs developed and validated. This study showed that the newly developed Xenopus laevis vitellogenin ELISA and liver slice bioassay have the potential to be employed in environmental monitoring programmes.
AFRIKAANSE OPSOMMING: Daar is toenemende besorgdheid dat afwykings in mens- en dierbevolkings voorkom as gevolg van blootstelling aan chemikalieë (hoofsaaklik mensgemaak) in die omgewing wat die normale werking van die endokrienstelsel versteur. Verskeie farmaseutiese, landbou- en industriële chemikalieë, wat as endokrienversteurders optree, is in die omgewing gevind. AI kan die vlakke van hierdie stowwe analities bepaal word, is dit belangrik om hulle biologiese aktiwiteit te evalueer. Hiervoor word diermodelle aangewend om toepaslike toetse daarvoor te ontwikkel. Hierdie toetse word baseer op biologiese merkers, spesifieke xenobioties-geïnduseerde fisiologiese reaksies, en is gewoonlik afwykings van sellulêre- of biochemiese komponente, -prosesse of - strukture. Vitellogeen ('n dooiervoorloper) is 'n lipoproteïenkompleks wat, onder estrogeenbeheer, in die lewer vervaardig word en in die plasma sirkuleer vir uiteindelike inkorporasie in ontwikkelende oësiete van vroulike, ovipare werweldiere. Aangesien daar min of geen vitellogeen in manlike diere geproduseer word, is die teenwoordigheid daarvan 'n aanduiding dat die dier aan estrogeniese omgewingsbesoedeling blootgestel is. In hierdie studie is die Platanna, Xenopus laevis, as model gebruik om die gevolge van estrogene op biochemiese en fisiologiese veranderlikes, wat met vitellogenese geassosieer word, te bestudeer. As vertrekpunt is die seisoenale voortplantingsiklus van die wyfie, in terme van vitellogeen en -estrogeen vlakke in die plasma en aktiwiteit van die ovaria bepaal. Daar is aangetoon dat die estrogeen- en vitellogeenvlakke in die plasma met die ovariumsiklus, wat gedurende die lente hoogtepunte bereik, korreleer. Alhoewel daar seisoenaliteit bestaan, was daar dwarsdeur die jaar wyfies wat ovarium dooierneerlegging getoon het. Verhoging in estrogeenvlakke het vitellogeenpieke en rypwording van die ovaria voorafgegaan. Lipoproteïenprofiele, sowel as die cholesterol- , trigliseried- en fosfolipiedkonsentrasies in die plasma is bepaal en daar is aangetoon dat estrogeen hierdie medeveranderlikes in só 'n mate affekteer dat hulle as bykomende biomerkers vir estrogeenblootstelling in besoedelingstudies gebruik kan word. In vitro Xenopus laevis lewersnitte in die weefselkultuur omgewing is ondersoek om 'n biotoets te onwikkel vir die gebruik in vinnige estrogenisiteits-toetsing van watermonsters en chemise stowwe. Die mees gunstige kultuurtoestande is bepaal en die sensitiwiteit van estrogeenreaksies is verhoog deur lewer van mannetjies, wat vooraf met estrogeen behandel is, te gebruik. Hierdie biotoets se geldigheid is gestaaf en kan in roetine eerstevlaktoetsing van watermonsters gebruik word. Die gebruik van poliklonale teenliggaampies in 'n bestaande enzyme-linked immunosorbent assay (ELISA) is vervang deur spesiaal-ontwikkelde monoklonale anti-Xenopus laevis vitellogeen teenliggaampies. Uitgesoekte teenliggaampies, spesifiek teen die estrogeengeïnduseerde proteïene, is gekarakteriseer en ELISAs saamgestel en die geldigheid gestaaf. Hierdie studie het aangetoon dat die nuut-onwikkelde Xenopus laevis vitellogeen-ELISA en lewerkultuurbiotoets die potensiaal het om In omgewingsmoniteringprogramme gebruik te word.
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Sequeira, Suzanne Simone. "'1 NMR spectroscopic investigations into the metabolism and biochemical effects of model drugs and enzyme inducers in the rat." Thesis, Birkbeck (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342211.
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Moore, Leah Kathryn. "Neuronal viability and biochemical alterations after mechanical stretch injury an in vitro model of traumatic brain injury-induced neourodegeneration /." Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04072004-180116/unrestricted/moore%5Fleah%5Fk%5F200312%5Fms.pdf.
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Jha, Sumit Kumar. "Model Validation and Discovery for Complex Stochastic Systems." Research Showcase @ CMU, 2010. http://repository.cmu.edu/dissertations/10.
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In this thesis, we study two fundamental problems that arise in the modeling of stochastic systems: (i) Validation of stochastic models against behavioral specifications such as temporal logics, and (ii) Discovery of kinetic parameters of stochastic biochemical models from behavioral specifications.
We present a new Bayesian algorithm for Statistical Model Checking of stochastic systems based on a sequential version of Jeffreys’ Bayes Factor test. We argue that the Bayesian approach is more suited for application do- mains like systems biology modeling, where distributions on nuisance parameters and priors may be known. We prove that our Bayesian Statistical Model Checking algorithm terminates for a large subclass of prior probabilities. We also characterize the Type I/II errors associated with our algorithm. We experimentally demonstrate that this algorithm is suitable for the analysis of complex biochemical models like those written in the BioNetGen language. We then argue that i.i.d. sampling based Statistical Model Checking algorithms are not an effective way to study rare behaviors of stochastic models and present another Bayesian Statistical Model Checking algorithm that can incorporate non-i.i.d. sampling strategies.
We also present algorithms for synthesis of chemical kinetic parameters of stochastic biochemical models from high level behavioral specifications. We consider the setting where a modeler knows facts that must hold on the stochastic model but is not confident about some of the kinetic parameters in her model. We suggest algorithms for discovering these kinetic parameters from facts stated in appropriate formal probabilistic specification languages. Our algorithms are based on our theoretical results characterizing the probability of a specification being true on a stochastic biochemical model. We have applied this algorithm to discover kinetic parameters for biochemical models with as many as six unknown parameters.
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Bermúdez, Mei-Ling. "Carnosine as a Mechanism-based Intervention in the Thy1-aSyn Mouse Model of Parkinson’s Disease: Neurobehavioral, Biochemical, and Bioinformatic Analyses." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543839362404126.
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Tokimatsu, Toshiaki. "Biochemical Roles of Oxalic Acid in Wood Decay Model Systems and Characteristics of a New Oxalic Acid Producing Enzyme Glyoxylate Dehydrogenase." Kyoto University, 1999. http://hdl.handle.net/2433/182430.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第7591号
農博第1030号
新制||農||773(附属図書館)
学位論文||H11||N3226(農学部図書室)
UT51-99-D208
京都大学大学院農学研究科林産工学専攻
(主査)教授 島田 幹夫, 教授 桒原 正章, 教授 中坪 文明
学位規則第4条第1項該当
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Pfeiffer, Brent J. "Role of Proa(2)I collagen chains and collagen crosslinking in thoracic aortic biochemical integrity during aging using the OIM mouse model." Diss., Columbia, Mo. : University of Missouri-Columbia, 2006. http://hdl.handle.net/10355/4397.
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Thesis (Ph. D.)--University of Missouri-Columbia, 2006.Title from title screen of research.pdf file (viewed on December 22, 2006). 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. Vita. "May 2006" Includes bibliographical references.
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Petrides, Andreas. "Advances in the stochastic and deterministic analysis of multistable biochemical networks." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/279059.
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This dissertation is concerned with the potential multistability of protein concentrations in the cell that can arise in biochemical networks. That is, situations where one, or a family of, proteins may sit at one of two or more different steady state concentrations in otherwise identical cells, and in spite of them being in the same environment. Models of multisite protein phosphorylation have shown that this mechanism is able to exhibit unlimited multistability. Nevertheless, these models have not considered enzyme docking, the binding of the enzymes to one or more substrate docking sites, which are separate from the motif that is chemically modified. Enzyme docking is, however, increasingly being recognised as a method to achieve specificity in protein phosphorylation and dephosphorylation cycles. Most models in the literature for these systems are deterministic i.e. based on Ordinary Differential Equations, despite the fact that these are accurate only in the limit of large molecule numbers. For small molecule numbers, a discrete probabilistic, stochastic, approach is more suitable. However, when compared to the tools available in the deterministic framework, the tools available for stochastic analysis offer inadequate visualisation and intuition. We firstly try to bridge that gap, by developing three tools: a) a discrete `nullclines' construct applicable to stochastic systems - an analogue to the ODE nullcines, b) a stochastic tool based on a Weakly Chained Diagonally Dominant M-matrix formulation of the Chemical Master Equation and c) an algorithm that is able to construct non-reversible Markov chains with desired stationary probability distributions. We subsequently prove that, for multisite protein phosphorylation and similar models, in the deterministic domain, enzyme docking and the consequent substrate enzyme-sequestration must inevitably limit the extent of multistability, ultimately to one steady state. In contrast, bimodality can be obtained in the stochastic domain even in situations where bistability is not possible for large molecule numbers. We finally extend our results to cases where we have an autophosphorylating kinase, as for example is the case with $Ca^{2+}$/calmodulin-dependent protein kinase II (CaMKII), a key enzyme in synaptic plasticity.
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Schleissing, Mary Rucker. "Biochemical and functional analysis after in utero delivery of recombinant adeno-associated virus to a mouse model of glycogen storage disease type II." [Gainesville, Fla.] : University of Florida, 2002. http://purl.fcla.edu/fcla/etd/UFE0000603.
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Lane, Emma Louise. "A behavioural and biochemical evaluation of the momoamine uptake inhibitor BTS 73 398 in the 6-hydroxydopamine lesioned rat model of Parkinson's disease." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411513.
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Hernandez, Gabriella Veronica, Victoria Alice Smith, Morgan Coffin, Daniel Columbus, Matthew Burd, Kimberly Sprayberry, Mark Edwards, et al. "Development of a Pediatric Model of Nafld in Neonatal Iberian Pigs." DigitalCommons@CalPoly, 2019. https://digitalcommons.calpoly.edu/theses/2097.
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The prevalence of non-alcoholic fatty liver disease (NAFLD) in children has increased over the past decades, creating a need for animal models that recapitulate the features of the pediatric disease. Iberian pigs have a leptin-resistant phenotype characterized by hyperleptinemia, hyperphagia, and extreme adipogenesis. We hypothesized that neonatal Iberian pigs fed a high fat high-fructose (HFF) diet will develop a pattern of liver injury resembling pediatric NAFLD. In addition, we sought to determine if a mixture of probiotics would prevent the disease. Animals were fed 1 of 4 diets containing (g/kg body weight × d) 0 g fructose, 11 g fat and 199 kcal (CON-N; n=8), 22 g fructose, 16 g fat and 300 kcal (HFF2-N; n=8), CON + probiotic (CON-P; n=6), or HFF2 + probiotic (HFF2-P; n=6) every 6 h for 70 d. The probiotic mixture (6.2 × 104 cfu/mL) contained Pediococcus acidilactici, Pediococcus pentosaceus, Lactobacillus plantarum and Bacillus amyloliquefaciens. Body weight was recorded every 3 d. Serum markers of liver injury and dyslipidemia were measured on d 40 and 65 at 2 h post feeding. Fasting leptin, insulin, glucose and homeostatic model assessment (HOMA) values were assessed on d 70. Liver and skeletal muscle (longissimus dorsi) were collected on d 70 for histology, triacylglyceride (TAG) quantification, relative gene expression, and Western blot analysis. Metabolomic analysis was performed on liver tissue and plasma. Body weight was not significantly greater in HFF fed pigs compared to CON. Leptin, alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase and total bilirubin were increased (P ≤ 0.001), and high and low density lipoproteins decreased (P ≤ 0.05) in HFF2-N and HFF2-P. Livers in HFF2-P and HFF2-N had higher relative weight and TAG (P ≤ 0.001), micro and macrovesicular steatosis, ballooning degeneration, Mallory-denk bodies, inflammation and necrosis, increased gene expression of TNFα, TGFβ, IL1α and PPARγ (P ≤ 0.001), and decreased ChREBP (P ≤ 0.001). A probiotic affect was seen as pigs fed CON-P and HFF2-P had higher insulin and HOMA values were increased (P ≤ 0.05). Western blot analysis showed dysregulation of autophagy in liver of pigs fed CON-P and HFF2-P, and in skeletal muscle of pigs fed CON-N and HFF2-N. Metabolomic analysis demonstrated dysregulation of one-carbon metabolism, the tricarboxylic acid cycle (TCA), the urea cycle, and amino acid metabolism of pigs fed HFF2 diets compared to CON diets. In conclusion, Iberian pigs fed a HFF diet recapitulate many pediatric NAFLD-associated features, in the absence of obesity and independently of probiotic supplementation, suggesting a potentially suitable model for pediatric NAFLD research. Furthermore, probiotic supplementation did not ameliorate the onset of NAFLD when fed in conjunction with a HFF diet.
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Pinart, Gilberga Mariona. "Time course of biochemical, biomechanical, and histological changes for the assesment of inflammation and remodelling in a bleomycin-induced murine model of lung injury." Doctoral thesis, Universitat de Barcelona, 2009. http://hdl.handle.net/10803/1140.
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Las enfermedades pulmonares intersticiales difusas (EPID), constituyen un grupo variado de trastornos inflamatorios difusos de las vías aéreas inferiores causadas por inflamación, fibrosis (cicatritzación) de las paredes alveolares y grosor del espacio intersticial. Como muchas de estas EPID dan lugar a la formación de fibrosis, también se las llama fibrosis pulmonar (FP). Tanto la fisiopatología de la enfermedad como los mecanismos bioquímicos que se desencadenan son poco conocidos. La lesión pulmonar inducida por fármacos como la bleomicina, es heterogénea y rápida en su inicio, con una fase de alveolitis inicial caracterizada por la presencia de edema intersticial y de infiltración de células inflamatorias como los neutrófilos, macrófagos y limfocitos, que a su vez conducirán a una proliferación de los fibroblastos. Después hay una segunda fase, más fibrótica, que se caracteriza por la deposición de colágeno y de otros componentes de la matriz extracelular que resultarán en una distorsión de la arquitectura pulmonar. Como creemos que los parámetros biomecánicos pueden ser de gran utilidad en el seguimiento de las estrategias terapéuticas así como también del conocimiento general de la historia natural de las EPID, queremos saber cuál es la influencia de la respuesta inflamatoria en las diferentes fases evolutivas de la FP sobre la biomecánica del parénquima. Por eso utilizamos un modelo murino de lesión pulmonar de dos semanas o de un mes de durada, inducida por dosis única o dosis repetidas de bleomicina respectivamente.
En el primer trabajo, utilizamos tiras de paánquima pulmonar para el estudio biomecánico (elastancia, resistencia (R0) e histeresividad (mi(0)) los días 3, 7 y 15 después de una instilación única sub-letal de bleomicina. Se analizaron también el impacto de la inflamación pulmonar (mieloperoxidasa (MPOL), índice de inflamación pulmonar (LI) y el contenido de agua pulmonar (WL)) y de la remodelación pulmonar (hidroxiprolina (HPL) y fibras elásticas) en los mismos días en los que se hizo el estudio mecánico. Los hallazgos más significativos sugieren que este modelo proporciona nuevas evidencias para la comprensión de la fisiopatología de la lesión pulmonar inducida por bleomicina y la relación entre los cambios inflamatorios y la mecánica del tejido pulmonar. Los parámetros disipativos del tejido pulmonar se vieron modificados después de la lesión: tanto R0 como mi(0) estuvieron correlacionadas con la MPOL, WL y LI. No encontramos correlaciones significativas entre HPL y los parámetros mecánicos, pero si de la elastina con mi(0) i el grosor de la paret alveolar.
En el segundo trabajo, usamos tiras de parénquima pulmonar para hacer el estudio mecánico el día 28 después de una instilación única sub-letal o después de tres dosis de bleomicina cada dos semanas. Se analizó el impacto de la inflamación pulmonar (MPOL y LI) y de la remodelación pulmonar (fibras de colágeno) en los mismos días en que se hizo el estudio mecánico. En el modelo de tres dosis repetidas por bleomicina se halló una infiltración de células inflamatorias, un incremento de la MPO y de las fibras de colágeno, la presencia de focos fibroblásticos y un aumento tanto de la elastancia (H) como de la amortiguación tisular (G), 28 dáas después de la última dosis. Sin embargo, en el modelo de dosis única, el colágeno aumentó sin que hubiesen cambios significativos en la mecánica pulmonar.
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Ly, Philip Tuan Thanh. "In vitro analysis of the biochemical pathways activated by cholesteryl glucoside in a motor neuron hybrid model of amyotrophic lateral sclerosis-parkinsonism dementia complex." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/31979.
Full textAbstract:
Steryl glycosides are a family of compounds commonly found in the environment with
unclear biological roles. Cycad seeds, a dietary link to the etiology of the Guamanian
amyotrophic lateral sclerosis-Parkinsonism dementia complex (ALS-PDC) have an abundant
amount of steryl glycosides. Previously, our laboratory demonstrated that several members
of the cycad-derived steryl glycosides have toxic properties. Cholesteryl glucosides (CG), a
variant form of the cycad-derived steryl glycosides have been found to induce cell death in
primary rat cortical neurons. However, other groups have demonstrated that CG can protect
fibroblast cells from heat shock. In the present study, we showed that the motor neuronderived
cell line, NSC34 cells, exposed to CG resulted in a concentration- and timedependent
reduction in cell viability. However, a brief exposure of CG for one hour to
NSC34 cells induced cytoprotection against serum deprivation stress. The Kinetworks™
KPSS-1.3 phosphosite screen was used to examine phosphorylation changes during CG
preconditioning and indicated elevated AktSer⁻⁴⁷³ phosphorylation. Suppression of CG-
stimulated Akt phosphorylation with pharmacological inhibitors abolished CG
preconditioning. Furthermore, the results indicated AktSer⁻⁴⁷³ phosphorylation via a PI3K-dependent
and independent way. Erk1, but not Erk2 phosphorylation at its activation site
was inhibited with CG treatment. The role of Erk1 inhibition in CG toxicity remains unclear.
JNK and p38 MAPK were activation were temporally delayed, but were found to not involved
in mediating cell death. A sub-population of NSC34 cells treated with CG for at least 4 days
displayed a differentiated phenotype with enlarged soma and extended neurites. Moreover,
focal neurite swellings with accumulated cytoskeletal proteins and disease-associated
phospho-Tau were observed. CG-treatment did not induce abnormal cytoplasmic
accumulation of TDP43, as seen in sporadic ALS and Guamanian ALS and PDC cases.
Trypan blue staining indicated that the treated-cells with abnormal morphology were viable.
Taken together, these results demonstrated that CG is toxic to NSC34 cells. As a cellular
response to stress, these cells upregulated survival signals and/or undergo differentiation to
resist CG toxicity. A better understanding of the biochemical pathways triggered by CG in
NSC34 cells may provide insights to a common aberrant mechanism underlying the cause
of neuronal death in ALS-PDC.Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
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Bou, Khalil Maroun. "Elucidation of the biochemical significance of GMb1 ganglioside in model membranes of perdeuterated 1,2-dimyristoyl-L-[alpha]-phosphatidylcholine : a Fourier Transform Infrared spectroscopic investigation." Thesis, University of Ottawa (Canada), 1999. http://hdl.handle.net/10393/8864.
Full textAbstract:
The monosialoganglioside GM1 is an anionic glycosphingolipid found ubiquitously in the plasma membrane of mammalian cells. Although its exact normal biological function(s) and physical properties are unknown, it is speculated that GM1 may play a role in calcium transport and synaptic transmission in neural tissues. Fourier Transform Infrared (FTIR) spectroscopy was employed to test the model of bovine brain GM1 ganglioside incorporated into perdeuterated dimyristoylphosphatidylcholine (DMPCd54) multilamellar dispersions. The interaction of Ca 2+ ions with the mixed DMPCd54/GM1 bilayers and its effect on the hydrogen bonding at the interfacial region was also investigated. No thermal phase transition was displayed by the GM1 micellar suspensions over the temperature range from 5 to 60°C, even at concentrations of 110 mg/ml. On the other hand, in the mixed DMPCd54 /GM1 multilamellar bilayers, both the acyl chains of GM1 and the perdeuterated hydrocarbon chains of DMPCd54 exhibited a single, cooperative gel to liquid crystalline phase transition, occurring at a higher temperature than in pure DMPCd54 dispersions. This suggests that the ceramide moiety of the glycolipid inserts into the hydrophobic core of the phospholipid bilayer and that the mixed liposomes consisted of a homogeneous mixture of GM1 and DMPCd54 molecules. GM1 had an ordering effect on the mixed bilayers that was further enhanced by the divalent cation C2+. Spectral changes of the amide I and ester carbonyl bands at the interfacial zone indicated a reduced hydrogen bonding of these groups in the mixed liposomal bilayers. Our results also suggested that the ceramide moiety of GM1 inserts into the lipid bilayer of shorter chain symmetric phospholipids and terminates at the bilayer center (i.e., no interdigitation), forcing the carbohydrate headgroup to protrude farther out of the bilayer surface to allow a better binding to Ca2+ ions than DMPCd54. The divalent cation increased the probability of hydrogen bonding at the interfacial region. It is strongly believed that GM1 is involved in the translocation of extracellular signals across the plasma membrane and that the glycolipid affects interfacial hydrogen bonding and local hydrophobicity of the cell surface, which might modulate various surface events such as cell/cell and cell/surface protein interactions.
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Hoffman, Jared D. "THE PREBIOTIC INULIN BENEFICIALLY MODULATES THE GUT-BRAIN AXIS BY ENHANCING METABOLISM IN AN APOE4 MOUSE MODEL." UKnowledge, 2018. https://uknowledge.uky.edu/pharmacol_etds/24.
Full textAbstract:
Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the gut, periphery, and in the case of scyllo-inositol, the brain. We found in E3FAD and E4FAD mice fed either a prebiotic or control diet for 4-months, that the consumption of the prebiotic inulin can beneficially alter the gut microbiota, modulate metabolic function, and dramatically increase scyllo-inositol in the brain. This suggests that the consumption of prebiotics can beneficially impact the brain by enhancing metabolism, helping to decrease AD risk factors.
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Bou, Khalil Maroun. "Elucidation of the biochemical significance of GM¦1 ganglioside in model membranes of perdeuterated 1,2-dimyristoyl-L-Ã-phosphatidylcholine, a Fourier transform infrared spectroscopic investigation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape7/PQDD_0015/MQ48138.pdf.
Full text
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Mélykúti, Bence. "Theoretical advances in the modelling and interrogation of biochemical reaction systems : alternative formulations of the chemical Langevin equation and optimal experiment design for model discrimination." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:d368c04c-b611-41b2-8866-cde16b283b0d.
Full textAbstract:
This thesis is concerned with methodologies for the accurate quantitative modelling of molecular biological systems. The first part is devoted to the chemical Langevin equation (CLE), a stochastic differential equation driven by a multidimensional Wiener process. The CLE is an approximation to the standard discrete Markov jump process model of chemical reaction kinetics. It is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. We observe that the CLE is not a single equation, but a family of equations with shared finite-dimensional distributions. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation, which is just the rank of the stoichiometric matrix. On the practical side, we show that in the case where there are m_1 pairs of reversible reactions and m_2 irreversible reactions, there is another, simple formulation of the CLE with only m_1+m_2 Wiener processes, whereas the standard approach uses 2m_1+m_2. Considerable computational savings are achieved with this latter formulation. A flaw of the CLE model is identified: trajectories may leave the nonnegative orthant with positive probability. The second part addresses the challenge when alternative, structurally different ordinary differential equation models of similar complexity fit the available experimental data equally well. We review optimal experiment design methods for choosing the initial state and structural changes on the biological system to maximally discriminate between the outputs of rival models in terms of L_2-distance. We determine the optimal stimulus (input) profile for externally excitable systems. The numerical implementation relies on sum of squares decompositions and is demonstrated on two rival models of signal processing in starving Dictyostelium amoebae. Such experiments accelerate the perfection of our understanding of biochemical mechanisms.
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Yan, Qiang. "Metabolic Engineering of Serratia marcescens." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5348.
Full textAbstract:
The potential value of the chitin biomass (e.g. food waste) is recently considered being ignored by landfill. Chitin can be a potential cheap carbon source for converting into value-added chemicals by microorganisms. Serratia marcescens is a chitinolytic bacterium that harbors endogenous chitinase systems. With goals of characterzing S. marcescens chitinolytic capabilities and applying S. marcescens to chemical production from chitin, my dissertation main content includes five chapters: 1) Chapter 1 highlights background information of chitin source, S. marcescens and potential metabolic engineering targets using chitin as a substrate; 2) Chapter 2 demonstrates that ChiR is a key regulator in regulating 9 chitinase-related genes in S. marcescens Db11 and manipulation of chiR can be a useful and efficient genetic target to enhance chitin utilization; 3) Chapter 3 reports the production of N-acetylneuraminic acid (Neu5Ac) from chitin by a bottom-up approach of engineering the nonconventional chitinolytic bacterium, Serratia marcescens, including native constitutive promoter characterization and transcriptional and translational pathway balancing; 4) Chapter 4 describes improvement of S. marcescens chitinolytic capability by an adaptive evolution approach; 5) Chapter 5 elucidates S. marcescens intracellular metabolite profile using a constraint-based genome-scale metabolic model (iSR929) based on genomic annotation of S. marcescens Db11. Overall, the dissertation work is the first report of demonstrating the concept of chitin-based CBP using S. marcescens and the computational model and genetic molecular tools developed in this dissertation are valuable but not limited to design-build-test of S. marcescens for contributing to the field of biological science and metabolic engineering applications.
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Alfonso, Durruty Marta Pilar. "Biosignificance of Harris lines as stress markers in relation to moderate undernutrition and bone growth velocity a New Zealand white rabbit model for the study of bone growth /." Diss., Online access via UMI:, 2008.
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Vallaster, Markus Parzival. "Intergenerational Effects of Nicotine in an Animal Model of Paternal Nicotine Exposure." eScholarship@UMMS, 2008. http://escholarship.umassmed.edu/gsbs_diss/913.
Full textAbstract:
Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends on short-term environmental challenges with low doses of nicotine prior to the LD50 application. The observed survival phenotype is not restricted to nicotine as drug of abuse, but also presents itself, when NIC offspring is challenged with a cocaine LD50 after acclimatization to low doses of either nicotine or cocaine. Functionally, NIC offspring metabolizes nicotine faster than control. Mechanistically, NIC offspring livers show global up-regulation of xenobiotic processing genes (XPG), an effect that is even more pronounced in primary hepatocyte cultures. Being known targets of Constitutive Androstane Receptor (CAR) and Pregnane X Receptor (PXR), these XPGs show higher baseline expression in naïve NIC offspring livers. Nicotine’s action on the brain’s reward circuitry does not appear to be of biological significance in our model system. Taken together, paternal nicotine exposure leads to a non-specific and conditional phenotype in male NIC offspring that may provide a general survival advantage against xenobiotic challenges.