subject:(Biochemistry Biophysics AND Structural Biology)

University of Tennessee – Knoxville

1. Crenshaw, William I. Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex.

Degree: MS, Biochemistry and Cellular and Molecular Biology, 2009, University of Tennessee – Knoxville

URL: http://trace.tennessee.edu/utk_gradthes/37

► The majority of chloroplast proteins are nuclear encoded and transcribed on cytosolic ribosomes, and therefore must be post-translationally imported into the chloroplast. Preproteins are directed… (more)

▼ The majority of chloroplast proteins are nuclear encoded and transcribed on cytosolic ribosomes, and therefore must be post-translationally imported into the chloroplast. Preproteins are directed to the chloroplast via a cleavable Nterminal extension known as a transit peptide. This transport is mediated by the Toc and Tic complexes (Translocon at the Outer/Inner Chloroplast envelope membrane), functioning in tandem to transport preproteins into chloroplasts relying on the hydrolysis of ATP and GTP. The Toc complex is composed of the β-barrel channel protein Toc75 and the homologous GTPase receptors Toc34 and Toc159. GTP hydrolysis is necessary for the formation of the early import intermediate, in which the transit peptide is inserted into the Toc channel, but the presence of internal ATP is the only energetic requirement for the later stages of translocation to occur, mediated by the stromal motor complex with an Hsp100 isoform hydrolyzing stromal ATP. The purpose of the current study is to characterize the change in stability and/or oligomeric status of the Toc complex with the incubation of nucleotides, analogs, proteins/peptides, etc. by blue native electrophoresis followed by 2d SDS-PAGE. The Toc complex ranges from ~800 kDa to greater than 1320 kDa for the proposed Toc/Tic supercomplex when no proteolytic degradation has occurred. Proteolytic degradation of Toc159 is correlated with the appearance of complexes with a mass ranging from 800 kDa to 440 kDa and below. Proteolytic degradation of Toc159 is more apparent in chloroplasts purified from older Pisum sativum plants. The results of the incubation of chloroplasts with GDP, GTP, and non-hydrolyzable analogs before analysis by 2d electrophoresis followed by western blot hybridization suggest that the loading of the GTPase receptors with nucleotide triphosphate results in the increased association of Toc components in complexes in the size range of 880- 630 kDa. Advisors/Committee Members: Barry D. Bruce, Gladys Alexandre, Beth C. Mullin.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Crenshaw, W. I. (2009). Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex. (Thesis). University of Tennessee – Knoxville. Retrieved from http://trace.tennessee.edu/utk_gradthes/37

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Crenshaw, William I. “Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex.” 2009. Thesis, University of Tennessee – Knoxville. Accessed January 21, 2019. http://trace.tennessee.edu/utk_gradthes/37.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Crenshaw, William I. “Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex.” 2009. Web. 21 Jan 2019.

Vancouver:

Crenshaw WI. Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex. [Internet] [Thesis]. University of Tennessee – Knoxville; 2009. [cited 2019 Jan 21]. Available from: http://trace.tennessee.edu/utk_gradthes/37.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Crenshaw WI. Characterization of the Toc complex by blue native PAGE:oligomeric and dynamic changes of the Toc complex. [Thesis]. University of Tennessee – Knoxville; 2009. Available from: http://trace.tennessee.edu/utk_gradthes/37

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Liu, Dan. Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition.

Degree: MS, Chemistry and Biochemistry, 2015, South Dakota State University

URL: http://openprairie.sdstate.edu/etd/1808

► This thesis is divided into two parts: investigation of the Mitsunobu reaction of bulky phenols and aliphatic alcohols to improve yield, and studies of… (more)

▼ This thesis is divided into two parts: investigation of the Mitsunobu reaction of bulky phenols and aliphatic alcohols to improve yield, and studies of lignin dimer model compound synthesis and catalysts of lignin decomposition reaction for optimizing degradation reaction conditions to increase product yields of value-added chemicals. In the first part of this thesis, Mitsunobu reaction of sterically hindered phenols and primary alcohols was investigated in detail to reveal the reason for the low yield of product (30-40%) and a solution to the problem was proposed and tested. In Mitsunobu alkyl aryl etherification reactions, alkylation of hydrazinedicarboxylate- a Mitsunobu by-product could be a side reaction. For essentially all Mitsunobu reactions in the literature, this side reaction is not a notable problem and good yields can be obtained with a wide range of solvents used. However, for the reactions of sterically hindered phenols and primary alcohols, this side reaction can significantly decrease the product yields. To suppress the side reaction and improve the product yields, solvent effect was studied and it was found that the yields are improved by using a weaker solvent, such as diethyl ether, instead of THF. In the second part of this thesis, synthesis of a lignin model compound (a dimer) and xiii study of its hydrothermal decomposition were conducted as an effort to explore effective methods to convert lignin, the largest renewable source of aromatics, into valuable chemicals. Since -O-4 bond is the predominant linkage in lignin, selective cleavage of this bond is sufficient to breakdown lignin into monomers and low oligomers which can be used directly for synthesis of certain materials such as adhesive resins. Lignin model compound with -O-4 bond has been synthesized through a four-step reaction scheme and the dimer decomposition using various catalysts has been studied. It is found that repolymerization (or condensation) happens at a relatively low temperature (120 °C) with or without a catalyst. This work points out the need to develop methods to suppress condensation reactions. Advisors/Committee Members: Cheng Zhang.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Liu, D. (2015). Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition. (Masters Thesis). South Dakota State University. Retrieved from http://openprairie.sdstate.edu/etd/1808

Chicago Manual of Style (16^th Edition):

Liu, Dan. “Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition.” 2015. Masters Thesis, South Dakota State University. Accessed January 21, 2019. http://openprairie.sdstate.edu/etd/1808.

MLA Handbook (7^th Edition):

Liu, Dan. “Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition.” 2015. Web. 21 Jan 2019.

Vancouver:

Liu D. Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition. [Internet] [Masters thesis]. South Dakota State University; 2015. [cited 2019 Jan 21]. Available from: http://openprairie.sdstate.edu/etd/1808.

Council of Science Editors:

Liu D. Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition. [Masters Thesis]. South Dakota State University; 2015. Available from: http://openprairie.sdstate.edu/etd/1808

University of Louisville

3. Clark, Jennifer. Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase.

Degree: MS, 2014, University of Louisville

URL: 10.18297/etd/1720 ; https://ir.library.louisville.edu/etd/1720

► Altered energy metabolism is an established hallmark of cancer cells. Fructose-2,6-bisphosphate is an allosteric activator of glycolysis and its concentration in a cell is… (more)

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Clark, J. (2014). Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase. (Masters Thesis). University of Louisville. Retrieved from 10.18297/etd/1720 ; https://ir.library.louisville.edu/etd/1720

Chicago Manual of Style (16^th Edition):

Clark, Jennifer. “Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase.” 2014. Masters Thesis, University of Louisville. Accessed January 21, 2019. 10.18297/etd/1720 ; https://ir.library.louisville.edu/etd/1720.

MLA Handbook (7^th Edition):

Clark, Jennifer. “Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase.” 2014. Web. 21 Jan 2019.

Vancouver:

Clark J. Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase. [Internet] [Masters thesis]. University of Louisville; 2014. [cited 2019 Jan 21]. Available from: 10.18297/etd/1720 ; https://ir.library.louisville.edu/etd/1720.

Council of Science Editors:

Clark J. Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase. [Masters Thesis]. University of Louisville; 2014. Available from: 10.18297/etd/1720 ; https://ir.library.louisville.edu/etd/1720

Carnegie Mellon University

4. Dykstra, Kaitlyn M. Yip1A structures the mammalian endoplasmic reticulum.

Degree: 2012, Carnegie Mellon University

URL: http://repository.cmu.edu/dissertations/140

► The mammalian endoplasmic reticulum (ER) is the largest organelle in the cell, extending from the nuclear envelope throughout the cell periphery. The ER houses a… (more)

▼ The mammalian endoplasmic reticulum (ER) is the largest organelle in the cell, extending from the nuclear envelope throughout the cell periphery. The ER houses a wide variety of vital cell processes within a single membrane bound organelle. In order to accommodate these functions and respond to the demands of the cell, the ER is partitioned into dynamically regulated subdomains, each with its own distinct structure. Despite the likely importance of ER structure for its functions, few proteins have been identified as having a direct role in maintaining the structure of the ER and the consequences of alteration of normal ER structure are not well understood. Here we identify Yip1A, a conserved membrane protein that cycles between the ER and early Golgi, as a likely regulator of ER organization. Yip1A depletion led to restructuring of ER membranes into micrometer-sized, concentrically stacked whorls. These structures are reminiscent of the ER whorls found in certain specialized secretory cell types, where the regulation and functional consequence of ER whorl formation is not understood. We found that membrane stacking and whorl formation after Yip1A depletion coincided with a marked slowing of coat protein (COP) II-mediated protein export from the ER. Furthermore, whorl formation driven by exogenous expression of an ER protein with no role in COPII function also delayed cargo export. Thus, it appears that Yip1A is required to prevent ER whorl formation and that whorl formation can in turn delay protein export from the organelle. Whether this is the function of ER whorls in tissues remains to be seen, however these results make Yip1A a good candidate for playing a role in their regulation. To obtain insight into how Yip1A regulates ER whorl formation and to determine whether the mechanism might be shared with the yeast homologue Yip1p, we carried out a systematic mutational analysis of all residues in the protein. Two discrete sites (E95 and K146) were crucial for the control of ER whorl formation by Yip1A. Notably, the same residues were previously shown to be important for Yip1p-mediated viability in yeast, indicating a shared mechanism. On the other hand, a third site (E89) also essential for yeast viability was dispensable for Yip1A function in regulating whorl formation. Thus Yip1p/Yip1A may possess at least two distinct essential functions only one of which is required for regulation of ER structure. Of note, the sites required for control of ER whorl formation by Yip1A were dispensable for the binding of Yip1p to its established binding partners Yif1p and Ypt1/31p, whereas the site required for Yip1p to bind the same partners was dispensable for ER structuring by Yip1A. Based on these observations, we speculate that the function of Yip1A in regulating whorl formation is mediated by one or more distinct and yet-to-be identified binding partners. Collectively, these findings indicate that a dispersed ER network is important for proper COPII-mediated protein export and that Yip1A has a conserved function between…

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dykstra, K. M. (2012). Yip1A structures the mammalian endoplasmic reticulum. (Thesis). Carnegie Mellon University. Retrieved from http://repository.cmu.edu/dissertations/140

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dykstra, Kaitlyn M. “Yip1A structures the mammalian endoplasmic reticulum.” 2012. Thesis, Carnegie Mellon University. Accessed January 21, 2019. http://repository.cmu.edu/dissertations/140.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dykstra, Kaitlyn M. “Yip1A structures the mammalian endoplasmic reticulum.” 2012. Web. 21 Jan 2019.

Vancouver:

Dykstra KM. Yip1A structures the mammalian endoplasmic reticulum. [Internet] [Thesis]. Carnegie Mellon University; 2012. [cited 2019 Jan 21]. Available from: http://repository.cmu.edu/dissertations/140.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dykstra KM. Yip1A structures the mammalian endoplasmic reticulum. [Thesis]. Carnegie Mellon University; 2012. Available from: http://repository.cmu.edu/dissertations/140

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

East Tennessee State University

5. Yan, Hui. Regulation of Acute and Chronic Immune Responses by β-Arrestin2.

Degree: PhD, Biomedical Sciences, 2016, East Tennessee State University

URL: https://dc.etsu.edu/etd/3049

► β-arrestin2, previously recognized as a facilitator for G-protein associated 7 TMR desensitization/ internalization, has now been appreciated as an independent signal transducer that regulates… (more)

▼ β-arrestin2, previously recognized as a facilitator for G-protein associated 7 TMR desensitization/ internalization, has now been appreciated as an independent signal transducer that regulates multiple cellular responses including inflammation. Cecal ligation and puncture procedure (CLP) induced septic shock is an acute inflammatory response characterized by uncontrolled systemic inflammation. Myocardial ischemia/reperfusion is a chronic sterilize inflammation that requires the reaction of macrophages, fibroblasts and cardiac stem cells for regeneration and remodeling of the infarcted myocardium. Restrained chronic stress is an immune suppression model in which the inactivation of macrophages may be involved. Here we showed β-arrestin2 overexpression inhibited CLP-induced heart dysfunction in septic shock, stabilized the cardiovascular system, and eventually promoted survival. Inhibition of the activation of p38 that downstream of the IL-6 pathway may be a key regulatory target for β-arrestin2. To rescue cardiomyocytes from ischemia and reperfusion injury, Sca-1+ CSC from Wide-type or β-arrestin2 Knockout mice were delivered to the risked area before reperfusion; β-arrestin2 was shown to be a required factor and a promoter for the differentiation of the cardiac stem cells. A β-arrestin2/miR-155/GSK3β pathway was identified in this study. TLR-9 is an important part of the innate immune system which has been shown to be regulated by β-arrestin2 in various inflammatory models. Here we found, the immune suppression induced by restrained stress is mediated by Toll-like receptor 9 (TLR-9). TLR-9 facilitated the elevation of IL-1β, IL-10 and IL-17 levels in serum and decrease of the levels of plasma IFN-γ. Furthermore, macrophage apoptosis was alleviated in TLR-9 deficiency mice. In summary, β-arrestin2 and associated proteins like TLR-9 are important regulators of the immune response in a variety of disease conditions. Therapeutic strategies should be generated to balance the inflammation and anti-inflammation response by modulating β-arrestin2 expression and functions.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yan, H. (2016). Regulation of Acute and Chronic Immune Responses by β-Arrestin2. (Doctoral Dissertation). East Tennessee State University. Retrieved from https://dc.etsu.edu/etd/3049

Chicago Manual of Style (16^th Edition):

Yan, Hui. “Regulation of Acute and Chronic Immune Responses by β-Arrestin2.” 2016. Doctoral Dissertation, East Tennessee State University. Accessed January 21, 2019. https://dc.etsu.edu/etd/3049.

MLA Handbook (7^th Edition):

Yan, Hui. “Regulation of Acute and Chronic Immune Responses by β-Arrestin2.” 2016. Web. 21 Jan 2019.

Vancouver:

Yan H. Regulation of Acute and Chronic Immune Responses by β-Arrestin2. [Internet] [Doctoral dissertation]. East Tennessee State University; 2016. [cited 2019 Jan 21]. Available from: https://dc.etsu.edu/etd/3049.

Council of Science Editors:

Yan H. Regulation of Acute and Chronic Immune Responses by β-Arrestin2. [Doctoral Dissertation]. East Tennessee State University; 2016. Available from: https://dc.etsu.edu/etd/3049

University of Tennessee – Knoxville

6. Bucci, Joel Cullen. Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1).

Degree: 2016, University of Tennessee – Knoxville

URL: https://trace.tennessee.edu/utk_graddiss/3896

► Plasminogen activator inhibitor type-1 (PAI-1) specifically inhibits the proteases tissue type plasminogen activator and urokinase plasminogen activator to control the activation of fibrinolysis. Vitronectin interacts… (more)

Subjects/Keywords: Biochemistry; Biophysics; Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bucci, J. C. (2016). Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1). (Doctoral Dissertation). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_graddiss/3896

Chicago Manual of Style (16^th Edition):

Bucci, Joel Cullen. “Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1).” 2016. Doctoral Dissertation, University of Tennessee – Knoxville. Accessed January 21, 2019. https://trace.tennessee.edu/utk_graddiss/3896.

MLA Handbook (7^th Edition):

Bucci, Joel Cullen. “Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1).” 2016. Web. 21 Jan 2019.

Vancouver:

Bucci JC. Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1). [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2016. [cited 2019 Jan 21]. Available from: https://trace.tennessee.edu/utk_graddiss/3896.

Council of Science Editors:

Bucci JC. Pinpointing the Molecular Basis for Metal Ion Effects on Plasminogen Activator Inhibitor-1 (PAI-1). [Doctoral Dissertation]. University of Tennessee – Knoxville; 2016. Available from: https://trace.tennessee.edu/utk_graddiss/3896

University of Tennessee – Knoxville

7. Yue, Yufei. Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials.

Degree: 2016, University of Tennessee – Knoxville

URL: https://trace.tennessee.edu/utk_graddiss/3984

► S-adenosyl methionine (SAM) dependent methylation process is universally found in all branches of life. It has important implications in mammalian pathogenesis and plant metabolism. The… (more)

▼ S-adenosyl methionine (SAM) dependent methylation process is universally found in all branches of life. It has important implications in mammalian pathogenesis and plant metabolism. The methyl transfer is normally catalyzed by SAM-dependent methyltransferases(MTases). Two MTases are studied in this dissertation: the 1,7-dimethylxanthine methyltransferase (DXMT) which involve in plant caffeine biosynthesis, and the protein arginine methyltransferase 5(PRMT5) that participates in eukaryotic posttranslational modification. The late phase of caffeine biosynthesis starts from the substrate xanthosine and ends with the product caffeine, with theobromine as an intermediate product. DXMT is a key enzyme in this process and catalyzes two methylation steps: 1)methylation of 7-methylxanthine to form theobromine; 2)methylation of theobromine to form caffeine. The catalytic mechanism and product promiscuity of DXMT is intriguing. In Chapter 1, the quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) and free energy simulations were performed to explain the dual catalytic roles of DXMT. Simulation results show that a histidine residue may act as a general base catalyst during methylations. PRMTs can work as modifiers for histones and methylate the substrate arginine, thus interfering with histone code orchestration. The product specificity of PRMTs refers to their ability to produce either symmetric di-methylarginine(SDMA), asymmetric di-methylarginine(ADMA) or mono-methylarginine(MMA). Understanding the product specificity of PRMTs is important since different methylations may cause distinctive, even inverse biological consequences. PRMT5 produces SDMA, as compared to PRMT1 and PRMT3 that produce ADMA. In Chapter 2, simulations of PRMT5 have drawn a theoretical insight into the catalytic difference between SDMA and ADMA. Neddylation is a type of eukaryotic Ubiquitin-like (UBL) protein modification that is essential in cell division and development. Unlike ubiquitin and other small ubiquitin-like modifiers which target variety of protein substrates, the UBL NEDD8 is highly selective on modifying cullin proteins and contributes to 10% ~20% of all cellular ubiquitination and ubiquitination-like modification. In Chapter 3, the crystal structure of a trapped E3-E2 ̴ NEDD8-CUL1 intermediate was used for modeling, and simulations were applied to investigate the catalytic mechanism of NEDD8 transfer from E2 to the substrate. Some important insights were observed that may be used to understand the functional properties of the enzyme.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yue, Y. (2016). Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials. (Doctoral Dissertation). University of Tennessee – Knoxville. Retrieved from https://trace.tennessee.edu/utk_graddiss/3984

Chicago Manual of Style (16^th Edition):

Yue, Yufei. “Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials.” 2016. Doctoral Dissertation, University of Tennessee – Knoxville. Accessed January 21, 2019. https://trace.tennessee.edu/utk_graddiss/3984.

MLA Handbook (7^th Edition):

Yue, Yufei. “Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials.” 2016. Web. 21 Jan 2019.

Vancouver:

Yue Y. Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials. [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2016. [cited 2019 Jan 21]. Available from: https://trace.tennessee.edu/utk_graddiss/3984.

Council of Science Editors:

Yue Y. Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials. [Doctoral Dissertation]. University of Tennessee – Knoxville; 2016. Available from: https://trace.tennessee.edu/utk_graddiss/3984

Iowa State University

8. Gogerty, David. Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function.

Degree: 2011, Iowa State University

URL: https://lib.dr.iastate.edu/etd/10353

► Dependence on petroleum for energy and petrochemical products has led to high energy costs, a polluted environment, the depletion of a finite resource (oil), and… (more)

▼ Dependence on petroleum for energy and petrochemical products has led to high energy costs, a polluted environment, the depletion of a finite resource (oil), and the reliance on hostile nations for our energy security. Biofuels promise to alleviate some or all of these issues but remain costly and inefficient to produce, and difficult to integrate into our existing transportation infrastructure. A renewable fuel molecule capable of replacing petroleum for our fuel and chemical industries is desired. Isobutene is an important commercial chemical used for the synthesis of butyl rubber, terephthalic acid, specialty chemicals, and a gasoline performance additive known as alkylate. Currently, isobutene is produced from petroleum and hence is nonrenewable. Here we report that the Saccharomyces cerevisiae mevalonate diphosphate decarboxylase (ScMDD) can convert 3-hydroxy-3-methylbutyrate (3-HMB) to isobutene. Whole cells of Escherichia coli producing ScMDD formed isobutene from 3-HMB at a rate of 154 pmol h-1 g cells-1. His6-ScMDD was purified by nickel affinity chromatography and shown to produce isobutene from 3-HMB at a rate of 1.33 pmol min-1 mg-1 protein. In contrast, no isobutene was detected from control cells lacking ScMDD, and controls showed that both His6-ScMDD and 3-HMB were required for detectable isobutene formation in enzyme assays. ScMDD was subjected to error-prone PCR and 2 improved variants were characterized, ScMDD1 (I145F) and ScMDD2 (R74H). Whole cells of E. coli producing ScMDD1 and ScMDD2 produced isobutene from 3-HMB at rates of 3000 and 5888 pmol h-1 g cells-1 which are 19- and 38-fold increases compared to cells producing His6-ScMDD. Although ScMDD was shown to be amenable to manipulation in order to increase its activity on 3-HMB, we estimate that a 106 fold increase in activity is needed for commercial application. Two novel methods were designed to increase enzyme activity – a mevalonate selection and an isobutene biosensor. The mevalonate selection yielded one variant with a 3.9-fold increase in isopentenol production from mevalonate over wild-type, to 186.6 nmol min-1 g cells-1, as well as a 51.6% increase in isobutene-formation. The isobutene biosensor was built and confirmed to respond to isobutene, toluene, and isoprene with induction ratios of 1.64, 3.58, and 1.3, respectively.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gogerty, D. (2011). Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/10353

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gogerty, David. “Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function.” 2011. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/10353.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gogerty, David. “Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function.” 2011. Web. 21 Jan 2019.

Vancouver:

Gogerty D. Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function. [Internet] [Thesis]. Iowa State University; 2011. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/10353.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gogerty D. Isobutene formation from 3-hydroxy-3-methylbutyrate (3-HMB) by the Saccharomyces cerevisiae diphosphomevalonate decarboxylase (ScMDD) and directed enzyme evolution to improve enzyme function. [Thesis]. Iowa State University; 2011. Available from: https://lib.dr.iastate.edu/etd/10353

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

9. Tong, Jiansong. Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis.

Degree: 2009, Iowa State University

URL: https://lib.dr.iastate.edu/etd/10975

► In the cell, there are about 60% of the total proteins are membrane and membrane-associated proteins. Exocytosis, or its reverse phase endocytosis, contains a variety… (more)

▼ In the cell, there are about 60% of the total proteins are membrane and membrane-associated proteins. Exocytosis, or its reverse phase endocytosis, contains a variety of membrane proteins such as synaptobrevin2, syntaxin-1A etc and membrane-associated proteins, for example SNAP25 and epsin1 etc. Synaptobrein2 is also called vesicle-associated protein or v-SANRE which interacts with t-SNAREs syntaxin-1A and SNAP25 binary complex to form a four helical-bundle complex, which was the minimal fusion machinery for synaptic vesicle fused with plasma membrane in neuron. In addition, many other proteins such as Munc18, synaptotagmin, complexin etc are essential regulators to control neuronal transmitter release spatially and temporally. Epsin1, a membrane-associated protein binding with the plasma membrane by interaction with lipid phosphatidylinositol 4, 5-biphosphate (PIP2), on the contrary, plays a role in the clathrin-mediated endocytosis process. The purpose of this work is to investigate the structures of TMD (transmembrane domain) of synaptobrevin2 and N-termini (residues 1-14) of ENTH domain of epsin1 by EPR (electron paramagnetic resonance) technique. In addition, lipid mixing assay with fluorescence dyes was also applied to mimic the kinetics of membrane fusion with recombinant SNARE proteins on the liposome in vitro. EPR studies with TMD of synaptobrevin2 revealed that TMD was characterized as a loose dimmer with interaction mostly at the N-half of TMD, while C-half interacted with each other to form a dimmer only on the vesicle with 40% cholesterol. Thus, a scissors mechanism exists for TMD of synaptobrevin2 with the stimulation of cholesterol molecule. Moreover, disulfide cross-linked lipid mixing assay confirmed different functions for these two confirmations of TMD. Meanwhile, the EPR work of N-termini of ENTH domain provided evidence that the N-termini of ENTH domain forms an amphiphilic helix when it inserts into the vesicle contained 3% of lipid PIP2. Our power saturation study unraveled the topology of this helix with hydrophobic residues L6 and M10 deep insertion into the membrane. Most interestingly, the work helps us to identify the anti-parallel dimerization of N-termini of ENTH domain on the surface of membrane. Functional studies both in vitro and in vivo confirmed that such a self-association of ENTH domains on the membrane surface plays an important role to tubulate the membrane during endocytosis process.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Tong, J. (2009). Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/10975

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Tong, Jiansong. “Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis.” 2009. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/10975.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Tong, Jiansong. “Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis.” 2009. Web. 21 Jan 2019.

Vancouver:

Tong J. Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis. [Internet] [Thesis]. Iowa State University; 2009. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/10975.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Tong J. Structural and functional studies with membrane-associated proteins in synaptic exocytosis and endocytosis. [Thesis]. Iowa State University; 2009. Available from: https://lib.dr.iastate.edu/etd/10975

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

10. Kakar, Smita. Structure and Reactivity of Hexacoordinate Hemoglobins.

Degree: 2010, Iowa State University

URL: https://lib.dr.iastate.edu/etd/11235

► The heme prosthetic group in hemoglobins is most often attached to the globin through coordination of either one or two histidine side chains. Those proteins… (more)

▼ The heme prosthetic group in hemoglobins is most often attached to the globin through coordination of either one or two histidine side chains. Those proteins with one histidine coordinating the heme iron are called “pentacoordinate” hemoglobins, a group represented by red blood cell hemoglobin and most other oxygen transporters. Those with two histidines are called “hexacoordinate hemoglobins”, which have broad representation among eukaryotes. Coordination of the second histidine in hexacoordinate Hbs is reversible, allowing for binding of exogenous ligands like oxygen, carbon monoxide, and nitric oxide. Research over the past several years has produced a fairly detailed picture of the structure and biochemistry of hexacoordinate hemoglobins from several species including neuroglobin and cytoglobin in animals, and the nonsymbiotic hemoglobins in plants. However, a clear understanding of the physiological functions of these proteins remains an elusive goal. The aim of this research was to understand physiological functions based on the molecular structure of plant hemoglobins. All plants contain hemoglobins that fall into distinct phylogenetic classes. The subset of plants that carry out symbiotic nitrogen fixation express hemoglobins that scavenge and transport oxygen to bacterial symbiotes within root nodules. These “symbiotic” oxygen transport hemoglobins are distinct in structure and function from the non-oxygen transport (“nonsymbiotic”) Hbs found in all plants. Hemoglobins found in two closely related plants present a paradox concerning hemoglobin structure and function. Parasponia andersonii is a nitrogen fixing plant that expresses a symbiotic hemoglobin (ParaHb) characteristic of oxygen transport hemoglobins in having a pentacoordinate ferrous heme iron, moderate oxygen affinity, and a relatively rapid oxygen dissociation rate constant. A close relative that does not fix nitrogen, Trema tomentosa, expresses hemoglobin (TremaHb) sharing 93% amino acid identity to ParaHb, but its phylogeny predicts a typical nonsymbiotic hemoglobin with a hexacoordinate heme iron, high oxygen affinity, and slow oxygen dissociation rate constant. We characterized heme coordination and oxygen binding in TremaHb and ParaHb, along with their crystal structures, to investigate whether or not two hemoglobins with such high sequence similarity are actually so different in functional behavior. Our results demonstrate distinct mechanisms for convergent evolution of oxygen transport in different phylogenetic classes of plant hemoglobins.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Kakar, S. (2010). Structure and Reactivity of Hexacoordinate Hemoglobins. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/11235

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kakar, Smita. “Structure and Reactivity of Hexacoordinate Hemoglobins.” 2010. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/11235.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kakar, Smita. “Structure and Reactivity of Hexacoordinate Hemoglobins.” 2010. Web. 21 Jan 2019.

Vancouver:

Kakar S. Structure and Reactivity of Hexacoordinate Hemoglobins. [Internet] [Thesis]. Iowa State University; 2010. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/11235.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kakar S. Structure and Reactivity of Hexacoordinate Hemoglobins. [Thesis]. Iowa State University; 2010. Available from: https://lib.dr.iastate.edu/etd/11235

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

11. Zhao, Wei. Impact of the innate immune response on mammary epithelia.

Degree: 2009, Iowa State University

URL: https://lib.dr.iastate.edu/etd/10585

► Lipocalin 2 (Lcn2) is a member of the lipocalin family, members of which are usually small extracellular proteins with the abilities of binding and transporting… (more)

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Zhao, W. (2009). Impact of the innate immune response on mammary epithelia. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/10585

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhao, Wei. “Impact of the innate immune response on mammary epithelia.” 2009. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/10585.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhao, Wei. “Impact of the innate immune response on mammary epithelia.” 2009. Web. 21 Jan 2019.

Vancouver:

Zhao W. Impact of the innate immune response on mammary epithelia. [Internet] [Thesis]. Iowa State University; 2009. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/10585.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhao W. Impact of the innate immune response on mammary epithelia. [Thesis]. Iowa State University; 2009. Available from: https://lib.dr.iastate.edu/etd/10585

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

12. Cheng, Haitao. Protein structure prediction and conformational transitions.

Degree: 2009, Iowa State University

URL: https://lib.dr.iastate.edu/etd/10488

► There is a critical need for protein structure and function prediction. Accurate protein secondary structure prediction is essential for many bioinformatics applications, including protein tertiary… (more)

▼ There is a critical need for protein structure and function prediction. Accurate protein secondary structure prediction is essential for many bioinformatics applications, including protein tertiary structure prediction. We developed an algorithm (Fragment Data Mining, FDM) for protein secondary structure prediction using fragments of known structures obtained by multiple sequence alignment (MSA). Its performance is excellent where high-score MSA matches are available. By combing it with GOR V, a new Consensus Database Mining (CDM) method was developed, which surpasses the performances of both FDM and GOR V. For each residue, it chooses to use either the result of FDM or GOR V depending upon the availability of high-score matches of MSA. A server has been set up to make CDM publicly accessible. It becomes more popular due to the reliability and efficiency of its performance, the simplicity of its use, and its potential for improvement with the rapidly growing number of determined structrues. Phosphorylation is the most important post translational modifications for cellular regulation and signal transduction. Upon phosphorylation, proteins can undergo obvious conformational changes. It is challenging to characterize these changes because of the high flexibility of phosphorylation regions and the difficulties in obtaining diffraction quality crystals. In the current study, we focused on the conformational changes of CDK2 due to phosphorylation at Thr160. We use CA-CB-side chain (CABS) modeling, Targeted Molecular Dynamics (TMD) and conventional molecular dynamics (MD) to simulate the structural transition and create transition pathways. Principal component analysis (PCA) of the trajectories and normal mode analysis (NMA) with anisotropic network model (ANM - an elastic network model) were used for trajectory analysis and performance comparisons. The CABS with appropriate constraint weights and TMD with proper force constants successfully simulated the conformational changes of CDK2 phosphorylation, including the formation of the arginine cluster, maintaining the geometrical relationships of the conserved residues, and the characteristic movement of the active loop (T loop). For conventional MD, we use the CABS modeling and energy optimization to contruct the missing segments lin the structure. CABS is, for the first time, used also to create transition pathways as well as to patch in the segment without determined coordinates. It proved especially valuable in the study of small localized conformational changes. The results show that CABS and TMD are both effective approaches for creating pathways of transitions due to phosphorylation. PCA showed significant overlaps with set of low frequency ANM normal modes. It is possible to explore the mechanisms of phosphorylation-induced conformational changes with these simulation methods and analysis methods.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Cheng, H. (2009). Protein structure prediction and conformational transitions. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/10488

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Cheng, Haitao. “Protein structure prediction and conformational transitions.” 2009. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/10488.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Cheng, Haitao. “Protein structure prediction and conformational transitions.” 2009. Web. 21 Jan 2019.

Vancouver:

Cheng H. Protein structure prediction and conformational transitions. [Internet] [Thesis]. Iowa State University; 2009. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/10488.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Cheng H. Protein structure prediction and conformational transitions. [Thesis]. Iowa State University; 2009. Available from: https://lib.dr.iastate.edu/etd/10488

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

13. Leelananda, Sumudu Pamoda. Protein sequence-structure relationships.

Degree: 2011, Iowa State University

URL: https://lib.dr.iastate.edu/etd/10344

► Physical characteristics of amino acids are responsible for the folding of protein sequences to their native structures. An understanding of protein sequence-structure relationships is required… (more)

▼ Physical characteristics of amino acids are responsible for the folding of protein sequences to their native structures. An understanding of protein sequence-structure relationships is required to solve the folding problem and it is one of the most important problems in computational structural biology. Even though there are tens of thousands of protein structures in the Protein Data Bank, it is not understood why they take their particular structures or why they are limited to a few thousands of folds. It is well known that protein structures are evolutionarily more conserved than sequences and that, often, sequences with low sequence identity can share the same fold. This leads to the concept of protein designability. The designability of a particular conformation is defined as the number of different sequences that fold to it giving unique minimum energy. Graph features of contact diagrams are employed here to describe the topology of lattice models of proteins and coarse-grained protein structures. The relationship between graphical features and designability of structures is explored here in various ways. It is found that there exists a relationship between some simple geometric graph features and designability. Highly designable structures can be distinguished from poorly designable structures based on those graphical features. This finding confirms the fact that the topology of a protein structure giving rise to its residue-residue interaction network is an important determinant of its designability. We learn that, the higher the designability of a structure is, the more diverse is its sequence space. However, there are conserved positions, which are more frequently conserved as either polar or hydrophobic. There is a marked difference between the hydrophobic/polar profiles of highly and poorly designable sequences, and thus, they become more clearly distinguishable. These profiles can be used to train machine learning algorithms to predict the designability of sequences.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Leelananda, S. P. (2011). Protein sequence-structure relationships. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/10344

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Leelananda, Sumudu Pamoda. “Protein sequence-structure relationships.” 2011. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/10344.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Leelananda, Sumudu Pamoda. “Protein sequence-structure relationships.” 2011. Web. 21 Jan 2019.

Vancouver:

Leelananda SP. Protein sequence-structure relationships. [Internet] [Thesis]. Iowa State University; 2011. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/10344.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Leelananda SP. Protein sequence-structure relationships. [Thesis]. Iowa State University; 2011. Available from: https://lib.dr.iastate.edu/etd/10344

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Iowa State University

14. Wang, Lijun. Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles.

Degree: 2011, Iowa State University

URL: https://lib.dr.iastate.edu/etd/12014

► Many highly ordered mineralized structures are created by living organisms that are often hierarchical in structure with fundamental structural elements at nanometer scales. The ability… (more)

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Wang, L. (2011). Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles. (Thesis). Iowa State University. Retrieved from https://lib.dr.iastate.edu/etd/12014

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Lijun. “Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles.” 2011. Thesis, Iowa State University. Accessed January 21, 2019. https://lib.dr.iastate.edu/etd/12014.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Lijun. “Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles.” 2011. Web. 21 Jan 2019.

Vancouver:

Wang L. Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles. [Internet] [Thesis]. Iowa State University; 2011. [cited 2019 Jan 21]. Available from: https://lib.dr.iastate.edu/etd/12014.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang L. Studies of the structure and function of Mms6, a bacterial protein that promotes the formation of magnetic nanoparticles. [Thesis]. Iowa State University; 2011. Available from: https://lib.dr.iastate.edu/etd/12014

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

15. Kudire, Anay Kumar. Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases.

Degree: MS, Chemistry and Biochemistry, 2015, South Dakota State University

URL: http://openprairie.sdstate.edu/etd/1821

► Hybrid materials take advantage of the unique properties of two single-phase materials (e.g., organic and inorganic) by bonding these materials together, producing a two-phase… (more)

Subjects/Keywords: Biochemistry; Biochemistry, Biophysics, and Structural Biology; Chemistry

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APA (6^th Edition):

Kudire, A. K. (2015). Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases. (Masters Thesis). South Dakota State University. Retrieved from http://openprairie.sdstate.edu/etd/1821

Chicago Manual of Style (16^th Edition):

Kudire, Anay Kumar. “Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases.” 2015. Masters Thesis, South Dakota State University. Accessed January 21, 2019. http://openprairie.sdstate.edu/etd/1821.

MLA Handbook (7^th Edition):

Kudire, Anay Kumar. “Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases.” 2015. Web. 21 Jan 2019.

Vancouver:

Kudire AK. Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases. [Internet] [Masters thesis]. South Dakota State University; 2015. [cited 2019 Jan 21]. Available from: http://openprairie.sdstate.edu/etd/1821.

Council of Science Editors:

Kudire AK. Synthesis of Functionalized Carboxylate Deposition Materials for DSSC and New Chromatography Stationary Phases. [Masters Thesis]. South Dakota State University; 2015. Available from: http://openprairie.sdstate.edu/etd/1821

University of Colorado

16. Alzahrani, Abeer Ahmed. Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks.

Degree: PhD, Chemistry & Biochemistry, 2014, University of Colorado

URL: http://scholar.colorado.edu/chem_gradetds/1

► The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under… (more)

▼ The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azidealkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction. The orthogonally and chemoselectivity of this reaction enable its wide utility across varied scientific fields. Despite numerous inherent advantages and widespread use for small molecule synthesis and solution-based polymer chemistry, it has only recently and rarely been utilized to form polymer networks. This work focuses on the synthesis, mechanisms, and unique attributes of the CuAAC reaction for the fabrication of functional polymer networks. The photo-reduction of a series of copper(II)/amine complexes via ligand metal charge transfer was examined to determine their relative efficiency and selectivity in catalyzing the CuAAC reaction. The aliphatic amine ligands were used as an electron transfer species to reduce Cu(II) upon irradiation with 365 nm light while also functioning as an accelerating agent and as protecting ligands for the Cu(I) that was formed. Among the aliphatic amines studied, tertiary amines such as triethylamine (TEA), tetramethyldiamine (TMDA), N,N,N’,N”,N”-pentamethyldiethylenetriamine (PMDTA), and hexamethylenetetramine (HMTETA) were found to be the most effective. The reaction kinetics were accelerated by increasing the PMDETA : Cu(II) ratio with a ratio of ligand to Cu(II) of 4:1 yielding the maximum conversion in the shortest time. The sequential and orthogonal nature of the photo-CuAAC reaction and a chain-growth acrylate homopolymerization were demonstrated and used to form branched polymer structures. A bulk, organic soluble initiation system consisting of a Cu(II) salt and a primary amine was also examined in both model reactions and in bulk polymerizations. The system was shown to be highly efficient, leading to nearly complete CuAAC polymerization at ambient temperature. Increasing the ratio of amine to copper from 1 to 4 increases the CuAAC reaction rate significantly from 4 mM/min for 1:1 ratio of Cu(II):hexyalmine to 14mM/min for 1:4 ratio. The concentration dependence of the amine on the reaction rate enables the polymerization rate to be controlled simply by manipulating the hexylamine concentration. Sequential thiol–acrylate and photo-CuAAC click reactions were utilized to form twostage reactive polymer networks capable of generating wrinkles in a facile manner. The click thiol- Michael addition reaction was utilized to form a cross-linked polymer with residual, reactive alkyne sites that remained… Advisors/Committee Members: Christopher N. Bowman, Jeffrey W. Stansbury.

Subjects/Keywords: Biochemistry; Biochemistry, Biophysics, and Structural Biology; Chemistry

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APA (6^th Edition):

Alzahrani, A. A. (2014). Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks. (Doctoral Dissertation). University of Colorado. Retrieved from http://scholar.colorado.edu/chem_gradetds/1

Chicago Manual of Style (16^th Edition):

Alzahrani, Abeer Ahmed. “Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks.” 2014. Doctoral Dissertation, University of Colorado. Accessed January 21, 2019. http://scholar.colorado.edu/chem_gradetds/1.

MLA Handbook (7^th Edition):

Alzahrani, Abeer Ahmed. “Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks.” 2014. Web. 21 Jan 2019.

Vancouver:

Alzahrani AA. Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks. [Internet] [Doctoral dissertation]. University of Colorado; 2014. [cited 2019 Jan 21]. Available from: http://scholar.colorado.edu/chem_gradetds/1.

Council of Science Editors:

Alzahrani AA. Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks. [Doctoral Dissertation]. University of Colorado; 2014. Available from: http://scholar.colorado.edu/chem_gradetds/1

University of Tennessee – Knoxville

17. Raval, Sherin R. A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes.

Degree: MS, Biochemistry and Cellular and Molecular Biology, 2014, University of Tennessee – Knoxville

URL: http://trace.tennessee.edu/utk_gradthes/3173

► Aminoglycosides have proven very useful in the treatment of infections; lately their effectiveness has been greatly reduced due to increasing resistance. Among many known… (more)

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Molecular Biology

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APA (6^th Edition):

Raval, S. R. (2014). A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes. (Thesis). University of Tennessee – Knoxville. Retrieved from http://trace.tennessee.edu/utk_gradthes/3173

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Raval, Sherin R. “A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes.” 2014. Thesis, University of Tennessee – Knoxville. Accessed January 21, 2019. http://trace.tennessee.edu/utk_gradthes/3173.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Raval, Sherin R. “A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes.” 2014. Web. 21 Jan 2019.

Vancouver:

Raval SR. A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes. [Internet] [Thesis]. University of Tennessee – Knoxville; 2014. [cited 2019 Jan 21]. Available from: http://trace.tennessee.edu/utk_gradthes/3173.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Raval SR. A step towards understanding of the molecular basis of ligand promiscuity in the aminoglycoside modifying enzymes. [Thesis]. University of Tennessee – Knoxville; 2014. Available from: http://trace.tennessee.edu/utk_gradthes/3173

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

McMaster University

18. Eleftheriou, Meneses Nikolas. The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening.

Degree: MSc, 2010, McMaster University

URL: http://hdl.handle.net/11375/12262

►

Sol-gel derived silica provides a bio-compatible material for the solid-phase entrapment of viable cells. A selection of E. coli cells containing unique promoter-linked GFP… (more)

Subjects/Keywords: Chemistry and Chemical Biology; Biochemistry, Biophysics, and Structural Biology; Chemistry; Biochemistry, Biophysics, and Structural Biology

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APA (6^th Edition):

Eleftheriou, M. N. (2010). The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/12262

Chicago Manual of Style (16^th Edition):

Eleftheriou, Meneses Nikolas. “The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening.” 2010. Masters Thesis, McMaster University. Accessed January 21, 2019. http://hdl.handle.net/11375/12262.

MLA Handbook (7^th Edition):

Eleftheriou, Meneses Nikolas. “The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening.” 2010. Web. 21 Jan 2019.

Vancouver:

Eleftheriou MN. The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening. [Internet] [Masters thesis]. McMaster University; 2010. [cited 2019 Jan 21]. Available from: http://hdl.handle.net/11375/12262.

Council of Science Editors:

Eleftheriou MN. The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening. [Masters Thesis]. McMaster University; 2010. Available from: http://hdl.handle.net/11375/12262

Florida International University

19. cao, nan. Structure and Mechanism of Mycobacterial Topoisomerase I.

Degree: PhD, Biochemistry, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3747 ; FIDC006890

► The enzyme DNA topoisomerase I is an essential enzyme that plays an important role in eukaryotic and prokaryotic cellular processes such as DNA replication,… (more)

▼ The enzyme DNA topoisomerase I is an essential enzyme that plays an important role in eukaryotic and prokaryotic cellular processes such as DNA replication, transcription, recombination and repair. Mycobacterium tuberculosistopoisomerase I (MtTOP1) is a validated drug target for antituberculosis treatment. Mycobacterial topoisomerase I regulates the topological constraints in chromosomes and helps in maintaining the growth of mycobacteria. The N- terminal domain (NTD) of mycobacterial topoisomerase I contains conserved catalytic domains that along with the active site Tyrosine are involved in cleaving and rejoining a single strand of DNA. Magnesium is required in DNA cleavage activity of type IA topoisomerases. The C-terminal domain (CTD) of mycobacterial topoisomerase I is divided into four subdomains (D5-D8) and a positively charged tail. Each subdomain has a GxxGPY sequence motif. The DNA binding, relaxation, cleavage, religation, catenation and decatenation ability of each subdomains of CTD were studied. The present study shows that each subdomain has its own characteristics. Subdomain D8 and D7 are responsible for maintaining the relaxation activity of mycobacterial topoisomerase I. Subdomain D5 is essential to maintain the DNA cleavage, religation, catenation and decatenation activity. A new crystal structure of MtTOP1-704t (amino acids A2-T704 containing NTD+D5 domains) was obtained. Structures with ssDNA substrate bound to the active site (Y342) in the presence and absence of Mg2+ were also investigated. Significant enzyme conformational changes upon DNA binding place the catalytic tyrosine in a pre-transition position for cleavage of a specific phosphodiester linkage to form a covalent intermediate. Meanwhile, the enzyme/DNA complex with Mg2+ bound at active site may present the post- transition state for religation in the enzyme’s multiple-state DNA relaxation activity. The critical function of a strictly conserved glutamic acid in acid-base catalysis of the DNA cleavage step was also demonstrated by site-directed mutagenesis. The present work provides new functional insights into the more stringent requirement for DNA rejoining versus cleavage by type IA topoisomerase, and further establishes the potential for select interference of DNA rejoining via specific inhibitors. Advisors/Committee Members: Yuk-Ching Tse-Dinh, Xiaotang Wang, Yuan Liu, Watson Lees, Kalai Mathee.

Subjects/Keywords: Biochemistry; Molecular Biology; Biophysics; Biochemistry; Molecular Biology; Other Biochemistry, Biophysics, and Structural Biology

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APA (6^th Edition):

cao, n. (2018). Structure and Mechanism of Mycobacterial Topoisomerase I. (Doctoral Dissertation). Florida International University. Retrieved from https://digitalcommons.fiu.edu/etd/3747 ; FIDC006890

Chicago Manual of Style (16^th Edition):

cao, nan. “Structure and Mechanism of Mycobacterial Topoisomerase I.” 2018. Doctoral Dissertation, Florida International University. Accessed January 21, 2019. https://digitalcommons.fiu.edu/etd/3747 ; FIDC006890.

MLA Handbook (7^th Edition):

cao, nan. “Structure and Mechanism of Mycobacterial Topoisomerase I.” 2018. Web. 21 Jan 2019.

Vancouver:

cao n. Structure and Mechanism of Mycobacterial Topoisomerase I. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2019 Jan 21]. Available from: https://digitalcommons.fiu.edu/etd/3747 ; FIDC006890.

Council of Science Editors:

cao n. Structure and Mechanism of Mycobacterial Topoisomerase I. [Doctoral Dissertation]. Florida International University; 2018. Available from: https://digitalcommons.fiu.edu/etd/3747 ; FIDC006890

Virginia Commonwealth University

20. Yuan, Fang. DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS.

Degree: MS, Biochemistry, 2013, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/466

► Lysophosphatidic acid (LPA), a naturally-occurring, simple phospholipid, is present at elevated levels in the blood and ascites of ovarian cancer patients. LPA is a ligand… (more)

▼ Lysophosphatidic acid (LPA), a naturally-occurring, simple phospholipid, is present at elevated levels in the blood and ascites of ovarian cancer patients. LPA is a ligand of seven cell surface G protein-coupled receptors. It has been known as an oncogenic growth factor in ovarian cancer and other types of human malignancies. However, the precise biological functions of LPA in ovarian oncogenesis remain to be fully elucidated. Our laboratory is interested in studying the potential role of LPA, as a tumor microenvironment factor, in regulation of cancer cell metabolism. A fundamental change associated with most cancer is the switch of glucose metabolism from mitochondrial oxidative phosphorylation to aerobic glycolysis, a phenomenon described by Otto Warburg nearly a century ago. This seems to be necessary to meet bioenergetic and biosynthetic demands of rapidly dividing tumor cells. However, the mechanism underlying the switch from aerobic respiration to aerobic glycolysis in cancer cells remains poorly understood. In this thesis project, my goal was to explore the effect of LPA on glycolysis and to compare LPA with other important growth factors in their capability to promote the glycolytic pathway in ovarian cancer cells. We demonstrated that LPA stimulated aerobic glycolysis as well as cell proliferation in ovarian cancer cell lines. The two parallel responses were LPA dose dependent. To determine whether LPA is unique in driving glycolysis, we compared the effect of LPA with other growth factors, including EGF, insulin and IGF-1 which are all involved in pathogenesis of ovarian cancer. While doses of these growth factors could be adjusted to achieve similar levels of cell proliferation, LPA and EGF were much more potent than insulin and IGF-1 in stimulation of glycolytic flux and lactate production. Therefore, we identified LPA and EGF as highly glycolytic factors relevant to the development and maintenance of the glycolytic phenotype of ovarian cancer cells. The next part of my study was focused on the molecular mechanism for the differential effects of LPA, EGF, insulin and IGF-1 on glycolytic metabolism. We used the glucose metabolism RT-PCR array to profile expression of glycolytic genes. The most remarkable change induced by LPA and EGF was the robust induction of hexokinase 2 (HK2) that stimulates irreversible entry of glucose to the glycolytic pathway. However, insulin and IGF-1 only weakly induced HK2 expression. Further experimental evidence using HK2 inhibitors indicated that HK2 up-regulation was the critical mediator of LPA-induced glycolysis. Further, the cells grown in LPA and EGF-stimulated conditions appear to show larger volume compared to insulin and IGF-1-treated cells, consistent with the hypothesis that active glycolysis contributes to biosynthetic processes to maintain cell sizes. Taken together, these findings of the current study revealed high glycolytic effects of LPA and EGF in ovarian cancer and the underlying HK2-mediated mechanism that distinguishes LPA and EGF from other growth… Advisors/Committee Members: Xianjun Fang.

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA (6^th Edition):

Yuan, F. (2013). DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS. (Thesis). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/466

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yuan, Fang. “DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS.” 2013. Thesis, Virginia Commonwealth University. Accessed January 21, 2019. https://scholarscompass.vcu.edu/etd/466.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yuan, Fang. “DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS.” 2013. Web. 21 Jan 2019.

Vancouver:

Yuan F. DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS. [Internet] [Thesis]. Virginia Commonwealth University; 2013. [cited 2019 Jan 21]. Available from: https://scholarscompass.vcu.edu/etd/466.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yuan F. DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS. [Thesis]. Virginia Commonwealth University; 2013. Available from: https://scholarscompass.vcu.edu/etd/466

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

21. Van, Danielle. Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer.

Degree: PhD, Biochemistry, 2011, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/265

► Ovarian cancer is the most lethal of all gynecological cancers. Current ovarian cancer drug regimens, including taxanes and platinum-based agents, are susceptible to chemoresistance necessitating… (more)

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA (6^th Edition):

Van, D. (2011). Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/265

Chicago Manual of Style (16^th Edition):

Van, Danielle. “Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer.” 2011. Doctoral Dissertation, Virginia Commonwealth University. Accessed January 21, 2019. https://scholarscompass.vcu.edu/etd/265.

MLA Handbook (7^th Edition):

Van, Danielle. “Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer.” 2011. Web. 21 Jan 2019.

Vancouver:

Van D. Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2011. [cited 2019 Jan 21]. Available from: https://scholarscompass.vcu.edu/etd/265.

Council of Science Editors:

Van D. Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer. [Doctoral Dissertation]. Virginia Commonwealth University; 2011. Available from: https://scholarscompass.vcu.edu/etd/265

University of California – Berkeley

22. Chao, Luke H. Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation.

Degree: Molecular & Cell Biology, 2010, University of California – Berkeley

URL: http://www.escholarship.org/uc/item/9bt8t2n7

► Cell signaling utilizes the frequency of calcium stimuli to produce diverse physiological outcomes. From fertilization of oocytes and cardiac facilitation, to muscle contraction and action… (more)

▼ Cell signaling utilizes the frequency of calcium stimuli to produce diverse physiological outcomes. From fertilization of oocytes and cardiac facilitation, to muscle contraction and action potential firing, periodic fluctuations in calcium levels play a key role in determining cell fate. During my thesis work, I studied a protein signaling complex that responds to the frequency of calcium stimuli: calcium/calmodulin dependent protein kinase II (CaMKII). The CaMKII holoenzyme is a dodecameric kinase assembly that activates and autophosphorylates in a manner dependent on the frequency of calcium stimuli. Its best-studied role is in the post-synaptic neuron, where it responds to calcium pulse frequencies to initiate changes important for Long Term Potentiation.My work investigated the activation mechanism of CaMKII, with the goal of understanding the enzyme's cooperative response to calcium-saturated calmodulin. This work elucidates the mechanism for CaMKII activation; by demonstrating that CaMKII is not a simple `coincidence detector' as previously postulated, by showing that CaMKII is cooperatively activated by calcium-saturated calmodulin, and by demonstrating that cooperative activation is mediated by the inter-subunit `capture' of regulatory segments. This work demonstrates that the cooperative response of CaMKII can by modulated by the length of the linker region where splice-form deletions and insertions occur. Similar modifications have been shown to shift the frequency-dependent activation of the enzyme, suggesting that our proposed mechanism enables the enzyme to tune its frequency response depending on developmental or tissue-specific expression. In addition, analysis of interactions exhibited by a peptide inhibitor of CaMKII revealed docking sites which other proteins, such as the NMDA-receptor, may utilize in order to localize and affect the frequency response of the CaMKII. Finally, I investigated the exchange of CaMKII subunits between holoenzyme complexes, and discuss the implications of such a process in prolonging the response to calcium stimuli beyond the lifespan of individual protein subunits.

Subjects/Keywords: Biophysics, General; Chemistry, Biochemistry; CaMKII; Structural Biology

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APA (6^th Edition):

Chao, L. H. (2010). Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/9bt8t2n7

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chao, Luke H. “Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation.” 2010. Thesis, University of California – Berkeley. Accessed January 21, 2019. http://www.escholarship.org/uc/item/9bt8t2n7.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chao, Luke H. “Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation.” 2010. Web. 21 Jan 2019.

Vancouver:

Chao LH. Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation. [Internet] [Thesis]. University of California – Berkeley; 2010. [cited 2019 Jan 21]. Available from: http://www.escholarship.org/uc/item/9bt8t2n7.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chao LH. Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation. [Thesis]. University of California – Berkeley; 2010. Available from: http://www.escholarship.org/uc/item/9bt8t2n7

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Iowa

23. Zhu, Yueming. Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells.

Degree: PhD, Free Radical and Radiation Biology, 2011, University of Iowa

URL: https://ir.uiowa.edu/etd/3026

► This thesis describes studies that are designed to investigates the hypothesis that <em>mitochondrial production of reactive oxygen species (O₂^*- and H₂O₂) cause oxidative stress… (more)

▼ This thesis describes studies that are designed to investigates the hypothesis that <em>mitochondrial production of reactive oxygen species (O₂^*- and H₂O₂) cause oxidative stress during PCB exposure and this increased production of ROS contributes to the biological effects of PCBs on cell proliferation in human breast and prostate epithelial cells.</em> Exponentially growing non-malignant human breast epithelial cells (MCF-10A) and non-malignant human prostate epithelial cells (RWPE-1) were treated with selected PCBs and their metabolites (PCB3, 77, 153, Aroclor and 4ClBQ). Results showed that PCBs and their metabolites could significantly inhibit MCF-10A and RWPE-1 cell growth as well as inducing clonogenic cell killing. These PCBs were also found to increase steady-state levels of mitochondrial O₂^*- and H₂O₂. Furthermore, the same PCBs were also found to induce alterations in SOD activities in MCF-10A and RWPE-1 cells. Finally, treatment with either N-acetyl-cysteine (NAC), or the combination of polyethylene glycol (PEG) conjugated CuZnSOD and PEG-catalase added 1 hour after PCBs, significantly protected MCF-10A and RWPE-1 cells from PCB-induced toxicity even when added following PCB exposure. Similar experiments were also accomplished using airborne PCBs treated RWPE-1 cells. 4-OH-PCB11, a metabolite of airborne PCB 11 is shown to lead to steady-state increases in superoxide and hydroperoxides in exponentially growing RWPE-1 human nonmalignant prostate epithelial cells. This increased level of ROS was accompanied by the inhibition of cell growth and clonogenic cell killing. Furthermore treatment of cells with antioxidants one hour following exposure to 4-OH-PCB11 was able to significantly diminish the toxicity in human prostate epithelial cells. These results strongly supported the hypothesis that exposure to PCBs or their metabolites can induce the cytotoxicity and alterations in cellular proliferation as well as causing oxidative stress in exponentially growing human breast and prostate epithelial cells. More importantly, the data also provide clear evidence that antioxidant manipulations after PCB exposure are capable of protecting human cells against PCB-induced cytotoxicity. Based on these observations, the long term goal of this work is to develop a mechanism based biochemical rationale for the development of pharmaceutical manipulations to protect humans from PCB intoxication. Advisors/Committee Members: Spitz, Douglas Robert (supervisor).

Subjects/Keywords: Other Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Zhu, Y. (2011). Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells. (Doctoral Dissertation). University of Iowa. Retrieved from https://ir.uiowa.edu/etd/3026

Chicago Manual of Style (16^th Edition):

Zhu, Yueming. “Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells.” 2011. Doctoral Dissertation, University of Iowa. Accessed January 21, 2019. https://ir.uiowa.edu/etd/3026.

MLA Handbook (7^th Edition):

Zhu, Yueming. “Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells.” 2011. Web. 21 Jan 2019.

Vancouver:

Zhu Y. Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells. [Internet] [Doctoral dissertation]. University of Iowa; 2011. [cited 2019 Jan 21]. Available from: https://ir.uiowa.edu/etd/3026.

Council of Science Editors:

Zhu Y. Polychlorinated biphenyl (PCB)-induced oxidative stress mediates cytotoxicity in human breast and prostate epithelial cells. [Doctoral Dissertation]. University of Iowa; 2011. Available from: https://ir.uiowa.edu/etd/3026

Virginia Commonwealth University

24. Seegar, Tom CM. TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING.

Degree: PhD, Biochemistry, 2010, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/2122

► The primary function of the vascular system is the maintenance of oxygen homeostasis for all metazoan tissue. Angiogenesis, the remodeling and maintenance of new blood… (more)

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA (6^th Edition):

Seegar, T. C. (2010). TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/2122

Chicago Manual of Style (16^th Edition):

Seegar, Tom CM. “TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING.” 2010. Doctoral Dissertation, Virginia Commonwealth University. Accessed January 21, 2019. https://scholarscompass.vcu.edu/etd/2122.

MLA Handbook (7^th Edition):

Seegar, Tom CM. “TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING.” 2010. Web. 21 Jan 2019.

Vancouver:

Seegar TC. TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2010. [cited 2019 Jan 21]. Available from: https://scholarscompass.vcu.edu/etd/2122.

Council of Science Editors:

Seegar TC. TIED TOGETHER: A MOLECULAR ROLE FOR TIE1 IN ANGIOPOIETIN TIE2 SIGNALING. [Doctoral Dissertation]. Virginia Commonwealth University; 2010. Available from: https://scholarscompass.vcu.edu/etd/2122

Virginia Commonwealth University

25. Dang, David. LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS.

Degree: MS, Biochemistry, 2009, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/1907

► Lysophosphatidic acid (LPA) is a naturally occurring bioactive lysophospholipid that mediates a broad range of cellular processes such as cell proliferation, survival, migration and invasion.… (more)

▼ Lysophosphatidic acid (LPA) is a naturally occurring bioactive lysophospholipid that mediates a broad range of cellular processes such as cell proliferation, survival, migration and invasion. LPA also plays a potential role in human oncogenesis as suggested by elevated expression of its receptors and its producing enzymes in malignant tissues. In the current study, we demonstrated that LPA is a potent mediator of interleukin-6 (IL-6) production in ovarian cancer. IL-6 is a pleiotropic cytokine which is thought to be an important mediator of ovarian cancer development and progression. Here, we demonstrated that IL-6 levels are indeed increased in the plasma of ovarian cancer patients as compared to normal women. The IL-6 concentrations in ascites of ovarian cancer patients are even higher than those present in the plasma samples. These results suggest that increased IL-6 are expressed and secreted by ovarian cancer cells, forming a gradient from the ascites to the blood. Ovarian cancer cells indeed produce IL-6 in culture. However, when these cells are starved in serum-free medium, they cease producing IL-6, suggesting that IL-6 is not constitutively expressed, but rather in response to exogenous factors present in serum. We showed that IL-6 expression is not driven by peptide growth factors such as insulin-like growth factor I or epidermal growth factor. Instead, IL-6 expression is most potently induced by the lysophospholipid growth factor LPA. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the IL-6 gene promoter through activation of the NF-kB and C/EBP transcription factors. LPA also induces tyrosine phosphorylation and activation of Stat-3, a well known intracellular effector of IL-6. However, blockade of IL-6 with a neutralizing antibody only slightly reduced Stat-3 phosphorylation in response to LPA, suggesting that LPA may induce Stat-3 directly or through secondary mediators other than IL-6. Together, these studies demonstrate the role of LPA in regulation of IL-6 production and the underlying mechanism in ovarian cancer. Advisors/Committee Members: Frank Fang.

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA (6^th Edition):

Dang, D. (2009). LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS. (Thesis). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/1907

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dang, David. “LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS.” 2009. Thesis, Virginia Commonwealth University. Accessed January 21, 2019. https://scholarscompass.vcu.edu/etd/1907.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dang, David. “LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS.” 2009. Web. 21 Jan 2019.

Vancouver:

Dang D. LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS. [Internet] [Thesis]. Virginia Commonwealth University; 2009. [cited 2019 Jan 21]. Available from: https://scholarscompass.vcu.edu/etd/1907.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dang D. LYSOPHOSPHATIDIC ACID IS A MEDIATOR OF INTERLEUKIN-6 PRODUCTION IN OVARIAN CANCER CELLS. [Thesis]. Virginia Commonwealth University; 2009. Available from: https://scholarscompass.vcu.edu/etd/1907

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Virginia Commonwealth University

26. zhang, qifang. Role of Jak/Stat pathway in the pathogenesis of breast cancer.

Degree: PhD, Biochemistry, 2010, Virginia Commonwealth University

URL: https://scholarscompass.vcu.edu/etd/41

► The Jak/Stat signaling cascade mediates cell proliferation, differentiation, survival, apoptosis and immune responses. Aberrant activation of this pathway mediates neoplastic transformation and abnormal growth of… (more)

▼ The Jak/Stat signaling cascade mediates cell proliferation, differentiation, survival, apoptosis and immune responses. Aberrant activation of this pathway mediates neoplastic transformation and abnormal growth of many malignancies including breast cancer, the most common cancer among women, and the second leading cause of cancer deaths in women in United States. The mechanism by which the Jak/Stat pathway modulates the pathogenesis of breast cancer is unclear. This dissertation elucidates roles of Jak/Stat members that mediate the pathogenesis of breast cancer. For these studies, we used 4T1 mouse mammary tumor cells as a model which mimics human breast cancer. First, we investigated the role of Tyk2 tyrosine kinase in the pathogenesis of breast cancer. Here we show for the first time that compared with wild type mice, Tyk2 -/- mice show increased tumor growth rate as well as metastatic disease and splenomegaly when inoculated with 4T1 breast cancer cells. Such increased tumorigenicity was associated with a significant decrease of IFNg production in 4T1 tumor-bearing Tyk2 deficient mice T cells compared with wild type (WT) mice. We demonstrated that NK cells or CD8+ T cells control tumor growth in both Tyk2-/- and WT mice, but neither Tyk2-/- NK cells alone nor Tyk2-/- CD8+ T cells alone do not contribute to enhanced tumor growth and metastatic disease of Tyk2-/- mice. Tumor-bearing Tyk2-/- mice have increased level of myeloid-derived suppression cells than tumor-bearing mice. Tyk2-/- MDSCs have a slight increase in suppression of T cell proliferation. Since elevated phosphorylation of Stat3 has been seen in human and murine breast cancer, and expression of Stat3 in the mitochondria (mitoStat3) appears to have important affects on cell growth, we studied the ability of Stat3 targeted to the mitochondria (MLS Stat3) to influence growth and metastasis of 4T1 cells. We show that a serine mutant of Stat3 expressed in the mitochondria (Stat3 S727A) inhibits the ability of 4T1 tumor cells to grow and metastasize. In contrast, a serine to aspartic acid mutant of Stat3 (S727D) enhances tumorigenesis. We found that expression of mitochondrial-targeted Stat3 does not affect cell growth rate in cell culture under normal conditions, however in low glucose, the serine to alanine mutant shows reduced growth rate and ability to invade. Moreover, we found that expression of mitochondrial-targeted Stat3 protects cells from hypoxia. Our data indicate that serine phosphorylation of mitochondrial-localized Stat3 is required for cell transformation. In summary, our studies provided new insights into the role of Stat3 in breast cancer and suggest new therapeutic targets for the treatment of this disease. Advisors/Committee Members: Andrew Larner.

Subjects/Keywords: Biochemistry, Biophysics, and Structural Biology; Life Sciences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

zhang, q. (2010). Role of Jak/Stat pathway in the pathogenesis of breast cancer. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://scholarscompass.vcu.edu/etd/41

Chicago Manual of Style (16^th Edition):

zhang, qifang. “Role of Jak/Stat pathway in the pathogenesis of breast cancer.” 2010. Doctoral Dissertation, Virginia Commonwealth University. Accessed January 21, 2019. https://scholarscompass.vcu.edu/etd/41.

MLA Handbook (7^th Edition):

zhang, qifang. “Role of Jak/Stat pathway in the pathogenesis of breast cancer.” 2010. Web. 21 Jan 2019.

Vancouver:

zhang q. Role of Jak/Stat pathway in the pathogenesis of breast cancer. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2010. [cited 2019 Jan 21]. Available from: https://scholarscompass.vcu.edu/etd/41.

Council of Science Editors:

zhang q. Role of Jak/Stat pathway in the pathogenesis of breast cancer. [Doctoral Dissertation]. Virginia Commonwealth University; 2010. Available from: https://scholarscompass.vcu.edu/etd/41

University of Pennsylvania

27. Zhang, Yao. Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design.

Degree: 2011, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/973

► Helix association provides an efficient model for studying the fundamental principles behind protein folding. It also serves as a suitable template for the design of… (more)

Subjects/Keywords: helix assocaiton; Biochemistry, Biophysics, and Structural Biology

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APA (6^th Edition):

Zhang, Y. (2011). Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/973

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Yao. “Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design.” 2011. Thesis, University of Pennsylvania. Accessed January 21, 2019. https://repository.upenn.edu/edissertations/973.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Yao. “Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design.” 2011. Web. 21 Jan 2019.

Vancouver:

Zhang Y. Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design. [Internet] [Thesis]. University of Pennsylvania; 2011. [cited 2019 Jan 21]. Available from: https://repository.upenn.edu/edissertations/973.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang Y. Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design. [Thesis]. University of Pennsylvania; 2011. Available from: https://repository.upenn.edu/edissertations/973

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Washington

28. Vittal, Vinayak. Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes.

Degree: PhD, 2015, University of Washington

URL: http://hdl.handle.net/1773/33103

► Thirty-five years ago, during its initial discovery, the field of ubiquitination could not have been more aptly named. In fact, as the study of ubiquitin… (more)

Subjects/Keywords: biochemistry; biology; biophysics; structural; ubiquitin; Biochemistry; Biophysics; biological chemistry

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vittal, V. (2015). Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes. (Doctoral Dissertation). University of Washington. Retrieved from http://hdl.handle.net/1773/33103

Chicago Manual of Style (16^th Edition):

Vittal, Vinayak. “Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes.” 2015. Doctoral Dissertation, University of Washington. Accessed January 21, 2019. http://hdl.handle.net/1773/33103.

MLA Handbook (7^th Edition):

Vittal, Vinayak. “Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes.” 2015. Web. 21 Jan 2019.

Vancouver:

Vittal V. Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes. [Internet] [Doctoral dissertation]. University of Washington; 2015. [cited 2019 Jan 21]. Available from: http://hdl.handle.net/1773/33103.

Council of Science Editors:

Vittal V. Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes. [Doctoral Dissertation]. University of Washington; 2015. Available from: http://hdl.handle.net/1773/33103

McMaster University

29. McManus, Simon A. CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES.

Degree: PhD, 2012, McMaster University

URL: http://hdl.handle.net/11375/12405

►

The process of in vitro selection has led to the isolation of many catalytic DNA molecules, called deoxyribozymes, which can catalyze a range of… (more)

▼

The process of in vitro selection has led to the isolation of many catalytic DNA molecules, called deoxyribozymes, which can catalyze a range of biologically-relevant reactions. Despite these advances, questions still remain as to why DNA, which seems more suited to information storage than catalysis can efficiently catalyze chemical reactions. In this thesis, a group of deoxyribozymes that can catalyze their own phosphorylation using NTP substrates are used a model system to study how DNA is able to fold into complex structures necessary for catalysis. Using a variety of structural probing techniques, these studies elucidated a common secondary structure shared by three deoxyribozymes, which do not appear to share a common ancestor sequence. This suggests that this motif may be most efficient motif to catalyze self-phosphorylation by DNA. It also more generally demonstrates that DNA can undergo convergent evolution to reach the same complex folding arrangement. A fourth deoxyribozyme was found to fold into a complex tertiary structure containing a novel quadruplex-helix pseudoknot motif. The finding of this pseudoknot and comparison with other quadruplexes found in other functional nucleic acids led us to investigate whether these stable motifs could be incorporated into nucleic acid libraries to improve the process of in vitro selection and give researchers a better chance of isolating functional nucleic acids. Design and characterization of structured libraries revealed that DNA libraries could be made in which the majority of sequences are folded into quadruplex arrangements. The incorporation of this quadruplex scaffold into DNA sequence libraries may ease the isolation of functional nucleic acids that contain this useful structural motif. In the final part of this thesis, a self-phosphorylating deoxyribozyme was converted from a tool for study of DNA structure to a sensor for GTP and Mn²⁺, demonstrating that deoxyribozyme substrates can be converted into targets for biosensors.

Doctor of Philosophy (PhD)

Advisors/Committee Members: Li, Yingfu, Biochemistry.

Subjects/Keywords: quadruplex; biosensor; DNAzyme; SELEX; Biochemistry, Biophysics, and Structural Biology; Biochemistry, Biophysics, and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McManus, S. A. (2012). CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/12405

Chicago Manual of Style (16^th Edition):

McManus, Simon A. “CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES.” 2012. Doctoral Dissertation, McMaster University. Accessed January 21, 2019. http://hdl.handle.net/11375/12405.

MLA Handbook (7^th Edition):

McManus, Simon A. “CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES.” 2012. Web. 21 Jan 2019.

Vancouver:

McManus SA. CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES. [Internet] [Doctoral dissertation]. McMaster University; 2012. [cited 2019 Jan 21]. Available from: http://hdl.handle.net/11375/12405.

Council of Science Editors:

McManus SA. CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES. [Doctoral Dissertation]. McMaster University; 2012. Available from: http://hdl.handle.net/11375/12405

McMaster University

30. Stalker, Leanne. CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION.

Degree: PhD, 2013, McMaster University

URL: http://hdl.handle.net/11375/12920

►

KDM5b acts as a transcriptional repressor through its ability to demethylate tri-methylated lysine (K) 4 on histone H3 (H3K4me3). Demethylation of this histone modification… (more)

▼

KDM5b acts as a transcriptional repressor through its ability to demethylate tri-methylated lysine (K) 4 on histone H3 (H3K4me3). Demethylation of this histone modification leads to transcriptional repression and downstream biological effects on gene expression. KDM5b is involved in the regulation of differentiation and can exert an oncogenic and a tumour suppressive role depending on cellular context, making it an attractive future target for pharmaceutical intervention. Work from our group has shown that KDM5b expression is linked to differentiation, and that recruitment of the enzyme does not always result in an alteration of H3K4me3. Additionally, work from our group, as well as others, has failed to observe H3K4me3 demethylation by KDM5b in nucleosomal preparations. We therefore hypothesized that KDM5b may exert its demethylase potential on alternative histone targets and that KDM5b requires enzymatic co-factors to demethylate nucleosomes, similar to what is observed for other histone-modifying proteins. In this thesis, we describe KDM5b as having an alternate histone target, di-methylated histone H2B lysine 43 (H2BK43me2). We show that this methyl mark is the primary target for KDM5b, and that the expression level of H2BK43me2 is directly related to the process of differentiation. We additionally present a novel co-factor for KDM5b, the co-repressor TLE4 of the Groucho/TLE family. The presence of TLE4 is required and sufficient to confer nucleosomal demethylase activity to KDM5b, a novel discovery for any of the KDM5 family members. Overall, this work has described both an additional KDM5b target, and detailed requirements for KDM5b nucleosomal demethylation, advancing our understanding of how this enzyme is regulated in vivo. The novel aspects of KDM5b regulation presented within this thesis provide a framework from which future studies can be designed. This work contributes to our overall understanding of epigenetic regulation and will potentially aid in the development of novel anti-cancer therapeutic strategies.

Doctor of Philosophy (PhD)

Advisors/Committee Members: Truant, Ray, Biochemistry.

Subjects/Keywords: demethylase; histone; KDM5; epigenetics; Biochemistry, Biophysics, and Structural Biology; Biochemistry, Biophysics, and Structural Biology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Stalker, L. (2013). CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION. (Doctoral Dissertation). McMaster University. Retrieved from http://hdl.handle.net/11375/12920

Chicago Manual of Style (16^th Edition):

Stalker, Leanne. “CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION.” 2013. Doctoral Dissertation, McMaster University. Accessed January 21, 2019. http://hdl.handle.net/11375/12920.

MLA Handbook (7^th Edition):

Stalker, Leanne. “CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION.” 2013. Web. 21 Jan 2019.

Vancouver:

Stalker L. CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION. [Internet] [Doctoral dissertation]. McMaster University; 2013. [cited 2019 Jan 21]. Available from: http://hdl.handle.net/11375/12920.

Council of Science Editors:

Stalker L. CHARACTERIZING THE FUNCTION AND REGULATORY MECHANISMS OF THE HISTONE DEMETHYLASE KDM5B: INSIGHTS INTO THE COMPLEXITY OF EPIGENETIC REGULATION. [Doctoral Dissertation]. McMaster University; 2013. Available from: http://hdl.handle.net/11375/12920

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Open Access Theses and Dissertations