subject:(Biochemistry Biophysics AND Structural Biology)

1. 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 (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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Liu D. Mitsunobu Reactions of Bulky Phenols and Lignin Model Dimer Synthesis & Decomposition. [Internet] [Masters thesis]. South Dakota State University; 2015. [cited 2020 Feb 16]. 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

2. 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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Clark J. Enzyme kinetics : 6-phosphofructo-2-kinase/2,6-bisphosphatase. [Internet] [Masters thesis]. University of Louisville; 2014. [cited 2020 Feb 16]. 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

3. 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 (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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Dykstra KM. Yip1A structures the mammalian endoplasmic reticulum. [Internet] [Thesis]. Carnegie Mellon University; 2012. [cited 2020 Feb 16]. 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

University of Tennessee – Knoxville

4. 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 (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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

5. 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 (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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Yue Y. Molecular Dynamics Simulations of Enzymes with Quantum Mechanical/Molecular Mechanical Potentials. [Internet] [Doctoral dissertation]. University of Tennessee – Knoxville; 2016. [cited 2020 Feb 16]. 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

East Tennessee State University

6. 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 (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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Yan H. Regulation of Acute and Chronic Immune Responses by β-Arrestin2. [Internet] [Doctoral dissertation]. East Tennessee State University; 2016. [cited 2020 Feb 16]. 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

Duquesne University

7. Ferraro, Nicholas. State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry.

Degree: PhD, Chemistry and Biochemistry, 2019, Duquesne University

URL: https://dsc.duq.edu/etd/1837

► The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically modulates inhibitory transmission by… (more)

▼ The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically modulates inhibitory transmission by antagonizing membrane depolarization through anion influx. Allosteric interactions between the receptor and its lipid surroundings affect receptor function, and cholesterol is essential for pLGIC activity. Human α1 GlyR was purified from baculovirus infected insect cells and reconstituted in unilamellar vesicles at cholesterol: lipid ratios below and above the cholesterol activity threshold with aliquots of azi-cholesterol. State-dependent crosslinking studies of receptors primarily in its resting (no glycine), desensitized (10mM glycine) and open (F207A/A288G, 30nM ivermectin) states were then performed at elevated cholesterol levels necessary for activity. After photoactivation, covalently crosslinked cholesterol-GlyR were trypsinized, mass fingerprinted by tandem mass spectrometry (MS-MS), and sites of cholesterol crosslinks in peptides were refined by targeted MS-MS. Within the GlyR apo state, cholesterol interactions differed as a function of membrane cholesterol concentration correlating to the chemical activity of cholesterol, suggesting two distinct conformations. Differential cholesterol crosslinking patterns between resting, desensitized, and open states were observed, highlighting state-dependent differences in GlyR lipid accessibility. Distinct state-dependent crosslinking patterns indicative of alterations in either the lipid environment and/or channel structure were observed throughout GlyR, most prominently observed in the M4 transmembrane helix, extracellular domain loops and regions nearing the bilayer interface, and the large intracellular M3-M4 loop. The changes in M4 accessibility (transition from surface-mapped crosslinking to regions of the helix less exposed when mapped) suggest an outward twisting motion and translocation towards the bilayer/lipids as GlyR allosterically transitions. Strikingly, crosslinking patterns within the M3-M4 loop offer insight into the generalized structure of this unresolved region in all current pLGIC structural models, by suggesting the crosslinked regions of this intracellular loop are intimately associated or buried within the lipid bilayer. Taken together, crosslinking coupled with MS-MS has the capability to accurately probe and define physiological protein frameworks which can aid in the refinement of allosteric modulation and current structural models. Advisors/Committee Members: Michael Cascio, Stephanie Wetzel, Skip Kingston, Jana Patton-Vogt.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Ferraro, N. (2019). State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry. (Doctoral Dissertation). Duquesne University. Retrieved from https://dsc.duq.edu/etd/1837

Chicago Manual of Style (16^th Edition):

Ferraro, Nicholas. “State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry.” 2019. Doctoral Dissertation, Duquesne University. Accessed February 16, 2020. https://dsc.duq.edu/etd/1837.

MLA Handbook (7^th Edition):

Ferraro, Nicholas. “State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry.” 2019. Web. 16 Feb 2020.

Vancouver:

Ferraro N. State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry. [Internet] [Doctoral dissertation]. Duquesne University; 2019. [cited 2020 Feb 16]. Available from: https://dsc.duq.edu/etd/1837.

Council of Science Editors:

Ferraro N. State-Dependent Mapping of GlyR-Cholesterol Interactions by Coupling Crosslinking with Mass Spectrometry. [Doctoral Dissertation]. Duquesne University; 2019. Available from: https://dsc.duq.edu/etd/1837

Eastern Illinois University

8. Gamage, Hashni Epa Vidana. Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans.

Degree: MS, Biological Sciences, 2019, Eastern Illinois University

URL: https://thekeep.eiu.edu/theses/4571

► Glutamate carboxypeptidase II (GCPII) is a transmembrane zinc metalloprotease expressed in a number of organisms: from yeast to worm to humans. In humans, GCPII… (more)

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Gamage, H. E. V. (2019). Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans. (Masters Thesis). Eastern Illinois University. Retrieved from https://thekeep.eiu.edu/theses/4571

Chicago Manual of Style (16^th Edition):

Gamage, Hashni Epa Vidana. “Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans.” 2019. Masters Thesis, Eastern Illinois University. Accessed February 16, 2020. https://thekeep.eiu.edu/theses/4571.

MLA Handbook (7^th Edition):

Gamage, Hashni Epa Vidana. “Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans.” 2019. Web. 16 Feb 2020.

Vancouver:

Gamage HEV. Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans. [Internet] [Masters thesis]. Eastern Illinois University; 2019. [cited 2020 Feb 16]. Available from: https://thekeep.eiu.edu/theses/4571.

Council of Science Editors:

Gamage HEV. Functional Characterization of Glutamate Carboxypeptidase II in Caenorhabditis elegans. [Masters Thesis]. Eastern Illinois University; 2019. Available from: https://thekeep.eiu.edu/theses/4571

Iowa State University

9. 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 (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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

10. 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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Leelananda SP. Protein sequence-structure relationships. [Internet] [Thesis]. Iowa State University; 2011. [cited 2020 Feb 16]. 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

11. 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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

Virginia Commonwealth University

12. Govinda Remesh, Soumya. STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM.

Degree: PhD, Physiology and Biophysics, 2014, Virginia Commonwealth University

URL: https://doi.org/10.25772/3HWQ-5T45 ; https://scholarscompass.vcu.edu/etd/3572

► Interferon (IFN) regulatory factor family member 4 (IRF4) is a transcription factor that serves specific roles in transcriptional regulation of IFN responsive genes and… (more)

▼ Interferon (IFN) regulatory factor family member 4 (IRF4) is a transcription factor that serves specific roles in transcriptional regulation of IFN responsive genes and is indispensable in B- & T-cell differentiation. IRF4 like the other members of the family has two major domains- the N-terminal DNA binding domain (DBD) essential for its recognition and binding to the Interferon Stimulated Response Element DNA sequence and a C-terminal Interferon activation domain (IAD) thought to maintain IRF4 in an auto-inhibited inactive state and is also critical in its activation. A putative unstructured linker connects the DBD and IAD. Activation in most members of the IRF family requires phosphorylation to induce homo and hetero-dimerization. In contrast, IRF4 functions primarily through ternary complex formation involving different proteins including PU.1 and MyD88. The IRF4IAD has a C-terminal auto-inhibitory region (AIR) that has been proposed to physically impede the DBD from interacting with DNA in the absence of its binding partner. To understand the activation mechanism in molecular detail we determined the crystal structure of the IAD of IRF4 and also performed small-angle X-ray scattering (SAXS) studies. Our data reveals that the surface electrostatics of IAD and presence of additional loops confers exclusivity to IRF4 in the IRF family. SAXS studies suggest that the AIR is structured and makes interactions with the putative linker. We also performed analytical ultracentrifugation studies, fluorescence anisotropy binding experiments and SAXS studies on full-length IRF4 as well as on constructs where the first 20 residues, exclusive to IRF4 or the AIR were removed. We observe that the first 20 residues are critical in decreasing the binding affinity of full-length IRF4 to DNA. In addition, the putative linker of IRF4 connecting the N- and C-termini appears to be a folded domain and interacts with AIR. Also, overall full-length IRF4 appears as an elongated molecule and the N- and the C-terminal domains are arranged on either ends of full-length IRF4. Moreover, there are no signs of huge conformational changes in the protein during the activation process. Taken together, based on our data we propose that there is no auto-inhibited state for IRF4. Furthermore, it is the binding affinity of full-length IRF4 that is increased in the presence of its binding partner most likely through modest conformational changes. Advisors/Committee Members: Dr. Carlos Escalante, Dr. Montserrat Samso, Dr. Qinglian Liu, Dr. Darrel Peterson, Dr. Xiang-Yang Wang.

Subjects/Keywords: Biochemistry; Biophysics; and Structural Biology

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APA (6^th Edition):

Govinda Remesh, S. (2014). STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/3HWQ-5T45 ; https://scholarscompass.vcu.edu/etd/3572

Chicago Manual of Style (16^th Edition):

Govinda Remesh, Soumya. “STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM.” 2014. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 16, 2020. https://doi.org/10.25772/3HWQ-5T45 ; https://scholarscompass.vcu.edu/etd/3572.

MLA Handbook (7^th Edition):

Govinda Remesh, Soumya. “STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM.” 2014. Web. 16 Feb 2020.

Vancouver:

Govinda Remesh S. STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2014. [cited 2020 Feb 16]. Available from: https://doi.org/10.25772/3HWQ-5T45 ; https://scholarscompass.vcu.edu/etd/3572.

Council of Science Editors:

Govinda Remesh S. STRUCTURAL STUDIES OF INTERFERON REGULATORY FACTOR 4: A MOLECULAR PERSPECTIVE OF ITS REGULATORY MECHANISM. [Doctoral Dissertation]. Virginia Commonwealth University; 2014. Available from: https://doi.org/10.25772/3HWQ-5T45 ; https://scholarscompass.vcu.edu/etd/3572

13. 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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

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

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

URL: https://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 https://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 February 16, 2020. https://scholar.colorado.edu/chem_gradetds/1.

MLA Handbook (7^th Edition):

Alzahrani, Abeer Ahmed. “Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks.” 2014. Web. 16 Feb 2020.

Vancouver:

Alzahrani AA. Copper-Catalyzed Azide Alkyne Cycloaddition Polymer Networks. [Internet] [Doctoral dissertation]. University of Colorado; 2014. [cited 2020 Feb 16]. Available from: https://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: https://scholar.colorado.edu/chem_gradetds/1

University of Tennessee – Knoxville

15. 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: https://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 https://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 February 16, 2020. https://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. 16 Feb 2020.

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 2020 Feb 16]. Available from: https://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: https://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

16. 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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Eleftheriou MN. The Entrapment of E. coli in Sol-Gel-Derived Silica for Compound Screening. [Internet] [Masters thesis]. McMaster University; 2010. [cited 2020 Feb 16]. 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

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

Degree: PhD, Biochemistry, 2018, Florida International University

URL: https://digitalcommons.fiu.edu/etd/3747 ; 10.25148/etd.FIDC006890 ; 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 ; 10.25148/etd.FIDC006890 ; FIDC006890

Chicago Manual of Style (16^th Edition):

cao, nan. “Structure and Mechanism of Mycobacterial Topoisomerase I.” 2018. Doctoral Dissertation, Florida International University. Accessed February 16, 2020. https://digitalcommons.fiu.edu/etd/3747 ; 10.25148/etd.FIDC006890 ; FIDC006890.

MLA Handbook (7^th Edition):

cao, nan. “Structure and Mechanism of Mycobacterial Topoisomerase I.” 2018. Web. 16 Feb 2020.

Vancouver:

cao n. Structure and Mechanism of Mycobacterial Topoisomerase I. [Internet] [Doctoral dissertation]. Florida International University; 2018. [cited 2020 Feb 16]. Available from: https://digitalcommons.fiu.edu/etd/3747 ; 10.25148/etd.FIDC006890 ; 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 ; 10.25148/etd.FIDC006890 ; FIDC006890

University of Pennsylvania

18. 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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Zhang Y. Exploring the World of Helix Association: Disease Mechanism, Basic Folding and Novel Design. [Internet] [Thesis]. University of Pennsylvania; 2011. [cited 2020 Feb 16]. 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 California – Berkeley

19. 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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Chao LH. Structural Studies of Calcium/Calmodulin Depenedent Protein Kinase II Activation. [Internet] [Thesis]. University of California – Berkeley; 2010. [cited 2020 Feb 16]. 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

Western Michigan University

20. Adiyodi Veetil, Sandhya N. Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic.

Degree: PhD, Chemistry, 2011, Western Michigan University

URL: https://scholarworks.wmich.edu/dissertations/475

► Type 2 diabetes is mediated by insulin resistance, the inability of insulin to elicit a normal biological response in insulin responsive tissues. Several cellular… (more)

▼ Type 2 diabetes is mediated by insulin resistance, the inability of insulin to elicit a normal biological response in insulin responsive tissues. Several cellular models have been utilized to determine the mechanism of induction of insulin resistance but questions remain unanswered. One model, implicates the products of the Hexosamine Biosynthetic Pathway (HBP) in the induction of insulin resistance under hyperglycemia. The major end product of HBP, UDP-GlcNAc, is the substrate for O-GlcNAc transferase, an enzyme that catalyzes the O-GlcNAcylation of numerous proteins. This modification may play a role in induction of insulin resistance and thus needs to be evaluated in different cell types. Therefore, we set out to test whether or not insulin resistance could be established in primary rat hepatocytes. To accomplish this we used a HBP precursor, glucosamine and first assessed whether or not insulin resistance was established by evaluating insulin's effect on a key signaling protein, Akt. Results indicate that the insulin induced phosphorylation of Akt was decreased in the presence of glucosamine when compared to the control, suggesting an insulin resistant state. Signal protein activation is very important for the insulin regulation of gene expression. If the activation of signal proteins is altered, then the effect on gene expression should also be altered. Results show that under glucosamine treatment, insulin was no longer able to control the gene expression of a number of key enzymes in major metabolic pathways. Additionally an increase in O-GlcNAc modified proteins under glucosamine compared to the control was observed and a number of these proteins were identified through LC-MS. Lastly, the effect of selenium, an insulin mimetic agent, was examined in this model system. The effects of selenium on the phosphorylation of the insulin signaling protein, Akt and on the expression of the key enzymes of the major metabolic pathways both under normal and insulin resistant conditions were examined. Results show that selenium is a potent insulin mimetic not only under the normal/control condition, but also under the insulin resistant condition as well. Advisors/Committee Members: Dr. Susan R. Stapleton, Dr. David S. Reinhold, Dr. Pamela Hoppe.

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

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APA (6^th Edition):

Adiyodi Veetil, S. N. (2011). Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic. (Doctoral Dissertation). Western Michigan University. Retrieved from https://scholarworks.wmich.edu/dissertations/475

Chicago Manual of Style (16^th Edition):

Adiyodi Veetil, Sandhya N. “Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic.” 2011. Doctoral Dissertation, Western Michigan University. Accessed February 16, 2020. https://scholarworks.wmich.edu/dissertations/475.

MLA Handbook (7^th Edition):

Adiyodi Veetil, Sandhya N. “Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic.” 2011. Web. 16 Feb 2020.

Vancouver:

Adiyodi Veetil SN. Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic. [Internet] [Doctoral dissertation]. Western Michigan University; 2011. [cited 2020 Feb 16]. Available from: https://scholarworks.wmich.edu/dissertations/475.

Council of Science Editors:

Adiyodi Veetil SN. Glucosamine-Induced Insulin Resistance in Primary Rat Hepatocytes and the Role of Selenium as an Insulin Mimetic. [Doctoral Dissertation]. Western Michigan University; 2011. Available from: https://scholarworks.wmich.edu/dissertations/475

University of Iowa

21. 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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

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

Degree: PhD, Biochemistry, 2011, Virginia Commonwealth University

URL: https://doi.org/10.25772/2WAV-E830 ; 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 · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

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://doi.org/10.25772/2WAV-E830 ; 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 February 16, 2020. https://doi.org/10.25772/2WAV-E830 ; 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. 16 Feb 2020.

Vancouver:

Van D. Determining the mechanism of double-stranded RNA-induced cell death in ovarian cancer. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2011. [cited 2020 Feb 16]. Available from: https://doi.org/10.25772/2WAV-E830 ; 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://doi.org/10.25772/2WAV-E830 ; https://scholarscompass.vcu.edu/etd/265

Virginia Commonwealth University

23. Bhardwaj, Reetika. REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO.

Degree: PhD, Biochemistry, 2014, Virginia Commonwealth University

URL: https://doi.org/10.25772/4JHN-WG10 ; https://scholarscompass.vcu.edu/etd/629

► YKL-40 is a secreted glycoprotein, which is a shared biomarker of chronic inflammation and oncogenic transformation. Indeed, YKL-40 expression is up-regulated in many diseases… (more)

▼ YKL-40 is a secreted glycoprotein, which is a shared biomarker of chronic inflammation and oncogenic transformation. Indeed, YKL-40 expression is up-regulated in many diseases including multiple sclerosis, Alzheimer disease, viral encephalitis, HIV-associated dementia, brain infarction, and traumatic brain injury. YKL-40 is also expressed by several solid tumors, such as osteosarcoma, ovarian carcinoma and glioblastoma multiforme (GBM). It promotes the migration and invasion of astrocytes as well as GBM cells. Serum YKL-40 levels have been shown to directly correlate with tumor grade and potentially tumor burden in GBM. In contrast to the numerous reports documenting elevated expression of YKL-40, relatively little is known about inflammatory mediators and specific molecular mechanisms that control its expression. For my PhD project, I decided to elucidate the mechanism regulating YKL-40 expression in inflammation and to understand how YKL-40 mediates the migration and invasion of GBM cells in vivo. As per my first project, I found that YKL-40 expression is up-regulated in many inflammatory models such as irritant induced inflammation (turpentine), EAE (experimental autoimmune encephalomyelitis), irradiation induced brain inflammation and in the HIV-TAT overexpression model. YKL-40 expression is also up regulated in oligodendroglioma patient samples. We show that YKL-40 expression is activated by major pro-inflammatory cytokines including IL-1, IL-6, and OSM in astrocytes, and that the activation of YKL-40 expression by cytokines depends on the STAT and NF-κB regulatory elements located within the YKL-40 promoter. Additionally, we discovered that STAT3 is a major regulator of YKL-40 expression in response to the IL-6 family cytokines, including OSM. Indeed, both depletion of STAT3 expression or overexpression of dominant-negative STAT3 abolishes activation of YKL-40 expression. In contrast, although IL-1 activates NF-κB (p65/p50) in astrocytes, IL-1-induced YKL-40 expression is p65/p50 independent, and instead regulated by the RelB/p50 complexes. Interestingly, OSM promotes formation of p50/RelB complexes. In conclusion, we found that YKL-40 is up regulated by major pro-inflammatory cytokines during inflammation associated with various disease models. Thus, we uncovered the regulatory mechanism that governs the expression of YKL-40 during sterile inflammation. Next, I studied the role of YKL-40 in GBM in vivo. The major obstacle for treatment of GBM is the unique ability of GBM cells to diffusely infiltrate healthy brain tissue. GBM tumors express high levels of YKL-40, and we showed that administration of YKL-40 increases migration and invasion of U1242 cells in vitro. We used the U1242 cell line for our studies, due to its unique ability to form infiltrative tumors, which reflects the real brain pathology in GBM. Additionally, knock-down of YKL-40 suppresses the migration and invasion of GBM cells in vitro. To study this phenomenon in vivo, we utilized an inducible lentiviral vector containing shRNA to YKL-40.… Advisors/Committee Members: Tomasz Kordula.

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

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APA (6^th Edition):

Bhardwaj, R. (2014). REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/4JHN-WG10 ; https://scholarscompass.vcu.edu/etd/629

Chicago Manual of Style (16^th Edition):

Bhardwaj, Reetika. “REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO.” 2014. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 16, 2020. https://doi.org/10.25772/4JHN-WG10 ; https://scholarscompass.vcu.edu/etd/629.

MLA Handbook (7^th Edition):

Bhardwaj, Reetika. “REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO.” 2014. Web. 16 Feb 2020.

Vancouver:

Bhardwaj R. REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2014. [cited 2020 Feb 16]. Available from: https://doi.org/10.25772/4JHN-WG10 ; https://scholarscompass.vcu.edu/etd/629.

Council of Science Editors:

Bhardwaj R. REGULATION OF YKL-40 IN STERILE INFLAMMATION AND ITS ROLE IN GLIOBLASTOMA IN VIVO. [Doctoral Dissertation]. Virginia Commonwealth University; 2014. Available from: https://doi.org/10.25772/4JHN-WG10 ; https://scholarscompass.vcu.edu/etd/629

Virginia Commonwealth University

24. Marion, James D., Jr. THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY.

Degree: PhD, Biochemistry, 2013, Virginia Commonwealth University

URL: https://doi.org/10.25772/C0T2-F683 ; https://scholarscompass.vcu.edu/etd/487

► To defend against pathogen challenge, multi-cellular organisms mount an immune response that recognizes, sequesters and eradicates invading infectious agents. Critical to this safeguard is the… (more)

▼ To defend against pathogen challenge, multi-cellular organisms mount an immune response that recognizes, sequesters and eradicates invading infectious agents. Critical to this safeguard is the receptor-mediated detection of pathogens. Pathogen recognition then initiates a variety of signaling cascades that lead to the modulation of genes orchestrating an immune response. Toll-like receptor 3 (TLR3), a transmembrane receptor found in endosomes, is vital to the innate immune response against viruses. Double-stranded RNA (dsRNA) stimulation of TLR3 initiates a signaling cascade that leads to the production of type-I interferons and proinflammatory cytokines necessary to trigger the protective defenses of the immune system. Critical to this pathway is the activation of a kinase, TANK binding kinase 1 (TBK1), which phosphorylates the downstream transcription factors, IRF3 and IRF7, and leads to the production of IFN-beta. Interestingly, TBK1 function has been implicated in a number of other signaling cascades ranging from the insulin response and vesicle transport to xenophagy and anti-viral immunity. Increasingly, however, TBK1 dysregulation has been linked to autoimmune disorders and cancers, heightening the need to understand regulatory controls of TBK1. As a result, this dissertation investigates three components of the TLR3 signaling cascade in an attempt to further advance our understanding of the innate immune response. First, investigations into the adjuvant potential of dsRNA reveal that a 139bp dsRNA molecule is a viable candidate for vaccine adjuvant studies. Next, structural and functional studies of TLR3 with neutralizing antibodies provide evidence for a new TLR-signaling model in which dsRNA:TLR3 signaling units laterally cluster to achieve efficient signaling. Finally, cell-based assays, biophysical experiments and kinetic investigations into the mechanism by which an endogenous regulator of the TLR3 response, SIKE, functions, reveal that SIKE not only inhibits TBK1-mediated IRF3 phosphorylation, but is also a high affinity substrate. Findings from this study further suggest that SIKE regulates a critical catalytic hub not by direct repression of activity, but by redirection of catalysis through substrate affinity. Taken together, the results presented in this dissertation establish a foundation for building long-term studies on the function, regulation and viral subversion of the innate immune response. Advisors/Committee Members: Jessica K. Bell.

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

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APA (6^th Edition):

Marion, James D., J. (2013). THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY. (Doctoral Dissertation). Virginia Commonwealth University. Retrieved from https://doi.org/10.25772/C0T2-F683 ; https://scholarscompass.vcu.edu/etd/487

Chicago Manual of Style (16^th Edition):

Marion, James D., Jr. “THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY.” 2013. Doctoral Dissertation, Virginia Commonwealth University. Accessed February 16, 2020. https://doi.org/10.25772/C0T2-F683 ; https://scholarscompass.vcu.edu/etd/487.

MLA Handbook (7^th Edition):

Marion, James D., Jr. “THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY.” 2013. Web. 16 Feb 2020.

Vancouver:

Marion, James D. J. THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY. [Internet] [Doctoral dissertation]. Virginia Commonwealth University; 2013. [cited 2020 Feb 16]. Available from: https://doi.org/10.25772/C0T2-F683 ; https://scholarscompass.vcu.edu/etd/487.

Council of Science Editors:

Marion, James D. J. THE ACTIVATION, RECEPTOR COMPLEXING AND ENDOGENOUS REGULATION OF THE TYPE-I INTERFERON RESPONSE AS IT PERTAINS TO INNATE IMMUNITY. [Doctoral Dissertation]. Virginia Commonwealth University; 2013. Available from: https://doi.org/10.25772/C0T2-F683 ; https://scholarscompass.vcu.edu/etd/487

Virginia Commonwealth University

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

Degree: MS, Biochemistry, 2013, Virginia Commonwealth University

URL: https://doi.org/10.25772/F3JD-BD39 ; 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://doi.org/10.25772/F3JD-BD39 ; 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 February 16, 2020. https://doi.org/10.25772/F3JD-BD39 ; 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. 16 Feb 2020.

Vancouver:

Yuan F. DIFFERENTIAL EFFECTS OF GROWTH FACTORS ON GLYCOLYSIS IN OVARIAN CANCER CELLS. [Internet] [Thesis]. Virginia Commonwealth University; 2013. [cited 2020 Feb 16]. Available from: https://doi.org/10.25772/F3JD-BD39 ; 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://doi.org/10.25772/F3JD-BD39 ; 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

University of Washington

26. 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 (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 February 16, 2020. 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. 16 Feb 2020.

Vancouver:

Vittal V. Structural and Functional Characterization of Non-Canonical Ubiquitin Conjugating Enzymes. [Internet] [Doctoral dissertation]. University of Washington; 2015. [cited 2020 Feb 16]. 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

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

Degree: PhD, 2012, McMaster University

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

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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)

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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 February 16, 2020. http://hdl.handle.net/11375/12405.

MLA Handbook (7^th Edition):

McManus, Simon A. “CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES.” 2012. Web. 16 Feb 2020.

Vancouver:

McManus SA. CHARACTERIZATION AND APPLICATION OF SELF-PHOSPHORYLATING DEOXYRIBOZYMES. [Internet] [Doctoral dissertation]. McMaster University; 2012. [cited 2020 Feb 16]. 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

28. 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

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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)

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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 February 16, 2020. 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. 16 Feb 2020.

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 2020 Feb 16]. 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

University of California – San Francisco

29. Barad, Benjamin Asher. Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry.

Degree: Biophysics, 2019, University of California – San Francisco

URL: http://www.escholarship.org/uc/item/8t7048v8

► Proteins are complex macromolecules whose structure informs their function and regulation in difficult to predict ways. Understanding their shape, dynamics, and regulation all pose major… (more)

▼ Proteins are complex macromolecules whose structure informs their function and regulation in difficult to predict ways. Understanding their shape, dynamics, and regulation all pose major challenges in terms of collecting, analyzing, and interpreting data. In my dissertation I describe two contributions to data analysis for determining the structure and dynamics of proteins using novel approaches, as well as experimental work querying the function of an enzyme with a particularly recalcitrant substrate. In the first chapter of this dissertation, I develop a tool, EMRinger, for the emerging field of high resolution electron microscopy that takes advantage of prior physical information about model geometry to more effectively determine if the model is built correctly into the map. This work adapted the tool Ringer, which had been previously developed in the Alber lab, in order to identify the dihedral angle for side chains with the greatest density, and confirm that the distribution of those peak positions does not violate the constraints of side chain dihedral angles to rotameric positions. This approach allows for orthogonal validation of backbone position in density (using the side chain density as a “lever”), which generally improves with refinement and is among the most sensitive model-in-map validation tools available for high resolution electron microscopy. In the second chapter, I present progress on applying temperature jumps to folded proteins to quantify kinetics of the intrinsic motions in proteins that impact their function and regulation. Using a pulsed infrared laser, we raise the temperature of a protein solution in nanoseconds, and follow the progression of the structure of the protein using solution x-ray scattering. As the protein changes temperature, the conformational equilibrium of the protein shifts as higher energy states become more accessible. By following this progress over the nanoseconds, microseconds and milliseconds following the heating pulse, we are able to reconstruct the relaxation of the protein into its new comformational equilibrium. With this information, we can gain kinetic information about the conformational landscapes of our sample, and using mutations we correlate the rates we observe with existing structural models of dynamics that have been characterized by x-ray crystallography. In the third chapter, I investigate the mechanics of Acidic Mammalian Chitinase, which has the role of breaking down the recalcitrant polysaccharide chitin in the stomach and lungs of mammals. Mutations to acidic mammalian chitinase have previously been identified that lead to either protection against allergic asthma, and previous work has determined that these mutations lead to an increase in the activity of the enzyme. In order to better determine how these mutations affect activity, I developed new methods to assay chitinase activity. I use these methods to characterize the effects of the asthma-associated mutations, as well as investigating the role of the individual domains of acidic…

Subjects/Keywords: Biophysics; Biochemistry; Quantitative Biology; Structural Biology; Time Resolved Structural Biology

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

APA (6^th Edition):

Barad, B. A. (2019). Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/8t7048v8

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):

Barad, Benjamin Asher. “Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry.” 2019. Thesis, University of California – San Francisco. Accessed February 16, 2020. http://www.escholarship.org/uc/item/8t7048v8.

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

MLA Handbook (7^th Edition):

Barad, Benjamin Asher. “Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry.” 2019. Web. 16 Feb 2020.

Vancouver:

Barad BA. Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry. [Internet] [Thesis]. University of California – San Francisco; 2019. [cited 2020 Feb 16]. Available from: http://www.escholarship.org/uc/item/8t7048v8.

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

Council of Science Editors:

Barad BA. Maximizing Interpretability from Complex Experiments in Structural Biology and Biochemistry. [Thesis]. University of California – San Francisco; 2019. Available from: http://www.escholarship.org/uc/item/8t7048v8

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

University of Colorado

30. Swan, Jeffrey Alan. The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme.

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

URL: https://scholar.colorado.edu/chem_gradetds/123

► The hammerhead motif comprises a family of small self-cleaving ribozymes whose involvement in post-transcriptional regulation of gene expression is rapidly becoming more appreciated across… (more)

▼ The hammerhead motif comprises a family of small self-cleaving ribozymes whose involvement in post-transcriptional regulation of gene expression is rapidly becoming more appreciated across biological systems. Structural studies have revealed that the Schistosoma mansoni hammerhead achieves catalytic activity under physiological conditions via the formation of a highly specific tertiary interaction that positions the essential nucleotides to participate in acid-base chemistry. While this interaction forms efficiently in sub-millimolar concentrations of any divalent metal ion, a great deal of metal ion specificity is observed for enzymatic cleavage. Previous experiments have used single-molecule Förster resonance energy transfer (FRET) to interrogate this phenomenon, but have encountered structural dynamics that appear to be artificially coupled to the fluorescence intensity of the dye, raising the concern that the fluorophores are interfering with the intrinsic structural dynamics of the ribozyme. Here, alternative FRET labeling strategies are explored. Fluorophore positions within the interacting stems were tested for enzymatic activity, but modification resulted in diminished catalysis in all cases. The focus was therefore shifted to an orthogonal labeling strategy that tracks the formation of the tertiary interaction indirectly through the coaxial stacking of two non-interacting stems. Magnesium ion-dependent FRET was observed with this construct under single-molecule conditions, albeit with a smaller change in FRET upon conformational reorganization. The conformational states could be distinguished reliably by implementing an improved Hidden Markov modeling algorithm, allowing a side-by-side comparison between this and the original construct using smFRET. Ostensible differences in kinetics and heterogeneity, particularly for the unfolding transition, were observed for the structural dynamics of the two constructs. These results are formally consistent with steric inhibition of the tertiary interaction from the fluorophore, or that the natural structural dynamics are in some other way affected by fluorophore incorporation strategy. Alternatively, the differences could arise from incongruity between respective FRET labeling strategies' ability to distinguish conformational states of the ribozyme. Advisors/Committee Members: Arthur Pardi, Robert T. Batey, Joseph Falke.

Subjects/Keywords: fluorophore; hammerhead; heterogeneity; RNA; smFRET; structural dynamics; Biochemistry; Biochemistry, Biophysics, and Structural Biology; Biophysics

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

APA (6^th Edition):

Swan, J. A. (2014). The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme. (Masters Thesis). University of Colorado. Retrieved from https://scholar.colorado.edu/chem_gradetds/123

Chicago Manual of Style (16^th Edition):

Swan, Jeffrey Alan. “The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme.” 2014. Masters Thesis, University of Colorado. Accessed February 16, 2020. https://scholar.colorado.edu/chem_gradetds/123.

MLA Handbook (7^th Edition):

Swan, Jeffrey Alan. “The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme.” 2014. Web. 16 Feb 2020.

Vancouver:

Swan JA. The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme. [Internet] [Masters thesis]. University of Colorado; 2014. [cited 2020 Feb 16]. Available from: https://scholar.colorado.edu/chem_gradetds/123.

Council of Science Editors:

Swan JA. The Effect of Fluorescent Labeling on Structural Dynamics and Catalysis of the Schistosoma mansoni Hammerhead Riboszyme. [Masters Thesis]. University of Colorado; 2014. Available from: https://scholar.colorado.edu/chem_gradetds/123

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