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Penn State University
1.
Sacher, Joshua Ryan.
Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/13727
► In work directed toward a total synthesis of the Lycopodium alkaloid lycopladine H (21), several strategies have been explored based on key tandem oxidative dearomatization/Diels-Alder…
(more)
▼ In work directed toward a total synthesis of the Lycopodium alkaloid lycopladine H (21), several strategies have been explored based on key tandem oxidative dearomatization/Diels-Alder reactions of o-quinone ketals. Both intra- and intermolecular approaches were examined, with the greatest success coming from dearomatization of bromophenol 84b followed by cycloaddition of the resulting dienone with nitroethylene to provide the bicyclo[2.2.2]octane core 203 of the natural product. The C-5 center was established via a stereoselective Henry reaction with formaldehyde to form 228, and the C-12 center was set through addition of vinyl cerium to the C-12 ketone to give 272. A novel intramolecular hydroaminomethylation of vinyl amine 272 was used to construct the 8-membered azocane ring in intermediate 322, resulting in establishment of 3 of the 4 rings present in the natural product 21 in 9 steps from known readily available compounds.
Advisors/Committee Members: Steven M Weinreb, Dissertation Advisor/Co-Advisor, Raymond Lee Funk, Committee Member, Gong Chen, Committee Member, Ryan John Elias, Committee Member.
Subjects/Keywords: organic; synthesis; lycopodium; lycopladine; quinone ketal; oxidative dearomatization; hydroaminomethylation; Henry reaction
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APA (6th Edition):
Sacher, J. R. (2012). Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13727
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sacher, Joshua Ryan. “Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H.” 2012. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/13727.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sacher, Joshua Ryan. “Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H.” 2012. Web. 07 Mar 2021.
Vancouver:
Sacher JR. Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/13727.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sacher JR. Progress Toward a Total Synthesis of the Lycopodium Alkaloid Lycopladine H. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13727
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
2.
Zhang, Hua.
POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/19427
► This dissertation covers two important research by using synthetic polymers to address two major issues in fundamental research nowadays. The first important issue is the…
(more)
▼ This dissertation covers two important research by using synthetic polymers to address two major issues in fundamental research nowadays.
The first important issue is the emergence of “superbug” (antibiotic resistant bacteria) after traditional antibiotics have been used for several decades since the discovery of penicillin. “Superbug” infection are extremely hard to treat and it takes longer time for patients to cure. One of the counter measures is synthetic polymer antimicrobials. Both chapter 2 and 3 of this dissertation talk about using different synthetic strategies to produce different polymer antimicrobials for specific applications. The general antimicrobial mechanism of these polymers are discussed and the limitation of current research in this area is also mentioned. A detailed investigation on the antimicrobial activity and in vitro toxicity of both materials are carried out. In addition, the structure and property relationship of both materials are discussed which shows the possible directions in the future to improve the antimicrobial activity and/or minimize the toxicity.
The second interesting issue this dissertation covers is to utilize the stimuli responsive chemical reaction of synthetic polymers to power microscale devices to various application such as micro analytical devices, particle assembly control and drug delivery system. Previously, our group have demonstrated that we can harness the catalytic reaction of inorganic systems to fabricate self-powered micromotors and micropumps. However, the potential of polymer systems have not been studied yet. From chapter 4 to chapter 8 in this dissertation, different stimuli responsive polymer systems have been discussed and several self-powered micropumps and micromotors are built based on the polymer materials. Chapter 4 explores the possibility to use rapid depolymerization reaction to build the first example of self-powered micropump. Chapter 5 further demonstrates that dissociation of chemical bonds on the polymer side chains can also power these micropump devices. In the following chapter 6 and chapter 7, more practical application of these self-powered micropumps for intelligent drug delivery is proposed and studied. Particularly, using more bio-friendly stimuli such as glucose to trigger, this pumping action helps to create a glucose responsive drug delivery system. This system shows distinct advantages over traditional drug delivery system which operates on simple diffusion mechanism. Chapter 7 emphasizes another important yet barely studied feature of drug delivery system. This chapter exhibits the first example of rechargeable drug delivery system via reversible host/guest interactions. Finally, chapter 8 shows the rapid depolymerization from chapter 4 can also be used to power the movement of micromotor system. This chapter also shows two micromotor systems on different scales by using different fabrication techniques.
Advisors/Committee Members: Ayusman Sen, Dissertation Advisor/Co-Advisor, Harry R Allcock, Committee Member, Gong Chen, Committee Member, Qing Wang, Committee Member.
Subjects/Keywords: antimicrobial polymer; antibacterial polymer; stimuli responsive polymer; micromotor; micropump
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, H. (2013). POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19427
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhang, Hua. “POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES.” 2013. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/19427.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhang, Hua. “POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES.” 2013. Web. 07 Mar 2021.
Vancouver:
Zhang H. POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/19427.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhang H. POLYMER ANTIMICROBIAL AND SELF-POWERED MICRODEVICES. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19427
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
3.
Li, Puhui.
Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine.
Degree: 2013, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/20003
► Novel synthetic methodology involving 1,4-conjugate additions of a variety of carbon and hetero nucleophiles to nitrosoalkenes, generated in situ via the Denmark protocol using -chloro-O-silyloximes…
(more)
▼ Novel synthetic methodology involving 1,4-conjugate additions of a variety of carbon and hetero nucleophiles to nitrosoalkenes, generated in situ via the Denmark protocol using -chloro-O-silyloximes has been developed. This research demonstrated that both intermolecular and intramolecular conjugate additions of various carbon and heteroatom nucleophiles to nitrosoalkenes provide a novel method to access a variety of highly functionalized systems, some of which contain vicinal quaternary centers.
In the second part of the thesis, a synthesis of the structurally unique indole alkaloid tronocarpine has been initiated. A novel intermolecular tandem Sonogashira coupling/annulation reaction was used as a key strategy to construct the indole moiety of the metabolite, resulting in establishment of three of the five rings present in this natural product.
Advisors/Committee Members: Steven M Weinreb, Dissertation Advisor/Co-Advisor, Przemyslaw Maslak, Committee Member, Gong Chen, Committee Member, Herbert Herling Lipowsky, Committee Member.
Subjects/Keywords: nitrosoalkenes; tronocarpine
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, P. (2013). Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/20003
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Li, Puhui. “Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine.” 2013. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/20003.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Li, Puhui. “Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine.” 2013. Web. 07 Mar 2021.
Vancouver:
Li P. Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/20003.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Li P. Intermolecular And Intramolecular Conjugate Addition Of Carbon And Hetero Nucleophiles To Nitrosoalkene And An
approach To A Total Synthesis Of Tronocarpine. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/20003
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
4.
Mason, Jeremy David.
Total Synthesis of (±)-Alstoscholarisines A-E.
Degree: 2018, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/15645jdm505
► Total syntheses of the biologically active monoterpenoid indole alkaloids (±)-alstoscholarisines A-E (1-5) have been completed in twelve to fourteen steps. The approach commenced with a…
(more)
▼ Total syntheses of the biologically active monoterpenoid indole alkaloids (±)-alstoscholarisines A-E (1-5) have been completed in twelve to fourteen steps. The approach commenced with a Michael reaction between the enolate of indole ester 132 and α,β-unsaturated-N-sulfonyllactam 130 to form the C15-C16 bond of the alkaloids. A sequence involving chemoselective partial reduction of an N-sulfonyllactam and subsequent dehydration to an N-sulfonyliminium ion allows for the formation of a bridged aminal 162, which serves as a common intermediate for the synthesis of the five alkaloids. The degradation of a C20 allyl group to an aldehyde unit by a sequence of olefin transposition and oxidative cleavage allows for the formation of a lactol E ring. The stereochemistry of the α-methyl tetrahydropyran moiety is controlled by stereoselective introduction of axial hydride or methyl nucleophiles to intermediate oxocarbenium ions derived from the lactol. Final functional group manipulations allow for the completion of the syntheses of the alkaloids.
Advisors/Committee Members: Steven M Weinreb, Dissertation Advisor/Co-Advisor, Steven M Weinreb, Committee Chair/Co-Chair, Raymond Lee Funk, Committee Member, Gong Chen, Committee Member, Ming Tien, Outside Member.
Subjects/Keywords: Indole Alkaloids; Organic Synthesis
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Mason, J. D. (2018). Total Synthesis of (±)-Alstoscholarisines A-E. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/15645jdm505
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mason, Jeremy David. “Total Synthesis of (±)-Alstoscholarisines A-E.” 2018. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/15645jdm505.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mason, Jeremy David. “Total Synthesis of (±)-Alstoscholarisines A-E.” 2018. Web. 07 Mar 2021.
Vancouver:
Mason JD. Total Synthesis of (±)-Alstoscholarisines A-E. [Internet] [Thesis]. Penn State University; 2018. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/15645jdm505.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mason JD. Total Synthesis of (±)-Alstoscholarisines A-E. [Thesis]. Penn State University; 2018. Available from: https://submit-etda.libraries.psu.edu/catalog/15645jdm505
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
5.
Mcsweeney, Colleen Patricia.
RBM8a is required for normal cortical development.
Degree: 2017, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/14594cpm186
► The formation of the nervous system requires a balance between proliferation, differentiation and migration of neural progenitors, resulting in a neural network that mediates both…
(more)
▼ The formation of the nervous system requires a balance between proliferation, differentiation and migration of neural progenitors, resulting in a neural network that mediates both behaviors and autonomic functions. Here, we identified an exon junction complex protein , RBM8a, as a positive regulator of embryonic neural progenitor cell proliferation and differentiation. We determined that RBM8a knockdown (using in utero electroporation) leads to increased migration of neural progenitor cells (NPCs) to the cortical plate (CP), depletion of the NPC pool, and a decrease in the number of cells in the DNA synthesis phase of the cell cycle. Conversely, RBM8a overexpression leads to decreased migration of NPCs to the CP, expansion of the progenitor pool, and increased proliferation. In order to further explore the role of RBM8a in neurogenesis, we developed a conditional knockout mouse. We selectively knocked out RBM8a in neural stem cells, and the resulting mice exhibited microcephaly, early postnatal lethality, and altered distribution of neurons in the neocortex. We then assessed the novel role of RBM8a in the development of GABAergic interneurons in the cortex. We discovered that in addition to the profound phenotypes observed in mice with reduced expression of RBM8a in excitatory neurons previously described in (Mao et al., 2015), Nes-cre;RBM8afl/+mice show a significant decrease in the density of parvalbumin (PV)+ and neuropeptide Y (NPY)+ interneurons in the cortex, and PV+, NPY+ and somatostatin (SST)+ cells are abnormally distributed throughout the cortical layers. To determine the mechanism underlying this phenotype, we injected EdU into pregnant dams when the pups are E17 to label and quantitate the number of proliferating cells in the medial ganglionic eminence, where interneuron progenitors reside. We found a significant decrease in the number of cells in the S phase of the cell cycle. However, we did not observe any change in the number or distribution of Edu+/Nkx2.1+ progenitors (which become cortical interneurons). This indicates that the changes in interneuron number and distribution seen in adolescent mice (P17) are likely due to defects in proliferation migration of Nkx2.11+ progenitors from the GE to the cortex, or changes in cell fate. We then utilized Nkx2.1-cre mice to determine if the interneuron deficits were due to intrinsic changes in the progenitors, or due to cues received from other altered cell types. We determined that knockout of RBM8a in interneuron progenitors alone led to some changes in their distribution, but this effect was significantly less profound as when compared to the deletion of RBM8a from all neural stem cells (NSC)s. Therefore, we concluded that the phenotype is likely caused by some changes in intrinsic properties of Nkx2.1+ interneuron progenitors, but conceivably could also be due to changes in extrinsic cues from excitatory neurons and other cell types.
To determine if pyramidal cells of the cortex have normal electrophysiological properties, we conducted spontaneous…
Advisors/Committee Members: Yingwei Mao, Dissertation Advisor/Co-Advisor, Yingwei Mao, Committee Chair/Co-Chair, Bernhard Luscher, Committee Member, Gong Chen, Committee Member, David John Vandenbergh, Outside Member.
Subjects/Keywords: rbm8A; cortex; corticogenesis; development; microcephaly; autism
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Mcsweeney, C. P. (2017). RBM8a is required for normal cortical development. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/14594cpm186
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mcsweeney, Colleen Patricia. “RBM8a is required for normal cortical development.” 2017. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/14594cpm186.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mcsweeney, Colleen Patricia. “RBM8a is required for normal cortical development.” 2017. Web. 07 Mar 2021.
Vancouver:
Mcsweeney CP. RBM8a is required for normal cortical development. [Internet] [Thesis]. Penn State University; 2017. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/14594cpm186.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mcsweeney CP. RBM8a is required for normal cortical development. [Thesis]. Penn State University; 2017. Available from: https://submit-etda.libraries.psu.edu/catalog/14594cpm186
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
6.
Sun, Yazhou.
DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/13771
► Understanding the sequential information coded in DNA, RNA and proteins is important for both basic and applied researches in life sciences. Extensive efforts have been…
(more)
▼ Understanding the sequential information coded in DNA, RNA and proteins is important for both basic and applied researches in life sciences. Extensive efforts have been devoted to the research and development of DNA sequence analysis methods. The studies described in this dissertation explored new applications of existing methods in the context of the recent development of ultra-high throughput sequencing technologies. This dissertation also included new methods developed for studying gene families and human haplogroups. The theories, algorithms and tools for analyzing DNA sequence information concerning these studies are reviewed in Chapter 1 of this dissertation.
With the recent development in DNA sequencing technologies, came many new research opportunities. Great challenges also came along, mainly because of the large data size of the latest high throughput sequencing technologies. The potential of these new technologies was exploited to complete a 100,000 years old ancient polar bear mitochondrial genome. With this and some additional modern bear data, the matrilineal polar bear’s divergence time was estimated to be around 130,000 years ago, which is significantly older than some recent estimates. This estimate indicated that modern polar bear matrilineal ancestors adapted to the niche polar environment within 30,000 years after the speciation event and propagated along the entire Arctic Circle for the next 100,000 years. This recent speciation and rapid expansion process is analogous to the evolution and migration of modern humans. The lineage characteristics of the latter were also briefly studied using the same technologies. (Chapter 2)
Because of the increased efficiency from the latest sequencing technologies, more and more complete human mitochondrial genomes have been generated at an increasingly faster speed. Although mitochondrial haplogroups, and their classification and identification were widely used in human evolution and population studies, the current tools could not fully take advantage of the rapidly growing number of new mitochondrial genomes. An updated mitochondrial haplogroup classification system was thus developed with evolutionary models that incorporate the mitochondrial genomic variations within the human population. These variations have not been considered by previous methods, which could lead to incorrectly classified haplogroups. The variation parameters, including the whole-genome substitution rate (0.013 - 0.1 substitutions per generation), the rate heterogeneity among sites (Gamma distribution shape parameter α = 0.7078) and the percentage of invariant sites (64%), were estimated based on 7985 full-length human mitochondrial genome sequences. Haplogroups were then classified based on the corrected genetic distance estimation and modeled with position specific matrices. A new haplogroup identification system was developed based on the resulting matrices and the maximum-likelihood estimation (MLE) method, permitting fast and accurate haplogroup assignment for both known and new…
Advisors/Committee Members: Hong Ma, Dissertation Advisor/Co-Advisor, Stephen Wade Schaeffer, Committee Chair/Co-Chair, Gong Chen, Committee Member, Naomi S Altman, Special Member, Anton Nekrutenko, Committee Member.
Subjects/Keywords: DNA sequence analysis; DNA sequence analysis methods; DNA sequence analysis applications
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, Y. (2012). DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13771
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sun, Yazhou. “DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups.” 2012. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/13771.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sun, Yazhou. “DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups.” 2012. Web. 07 Mar 2021.
Vancouver:
Sun Y. DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/13771.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sun Y. DNA sequence analysis: new applications with high throughput sequencing and new methods in studying gene families and human haplogroups. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13771
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
7.
Han, Xinwei.
understanding gene expression and genetic recombination by next generation sequencing.
Degree: 2012, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/13792
► The introduction of next-generation sequencing technologies has been changing the landscape of biological research. The plummeting cost of massive sequencing not only leads to the…
(more)
▼ The introduction of next-generation sequencing technologies has been changing the landscape of biological research. The plummeting cost of massive sequencing not only leads to the flourishing of various genome projects, but also opens up many opportunities in previously uncharted areas, two remarkable examples of which are sequencing different individuals of the same species and sequencing transcriptomes. With the availability of multiple genome sequences from a population, it is possible to systematically catalog natural variations and, more importantly, investigate their genome-wide distribution to deduce functional elements through conservation or selection. Moreover, as genomic changes reflect evolution at work, the comprehensive map of natural variations serves as a basis for studying the properties and effects of evolutionary forces. For transcriptomics, sequencing has become a revolutionary way to characterize gene expression. It not only offers high replicability and unparalleled accuracy, but also requires less input material, enabling transcriptome study in tiny structures, and no prior knowledge of gene structure, allowing detection of unknown transcripts. Here, three sequencing-based studies are presented. One study explored natural variations between two Arabidopsis ecotypes, Col and Ler, and then investigated one crucial evolutionary force to shape variations, meiotic recombination. The other two studies investigated the small RNA transcriptome in Arabidopsis meiocytes and mRNA transcriptomes in developing mouse cortex.
In the first study, the sequencing and comparison between Col and Ler uncovered 249,171 SNPs, 58,085 small and 2,315 large indels, with highly correlated genome-wide distributions of SNPs and small indels. Disease resistance genes contain significantly more variations, suggesting adaptation to specific environmental niches. These variations were then used as markers to investigate meiotic recombinations, crossovers and gene conversions, in two tetrads, detecting 18 crossovers, 6 of which had an associated gene conversion event, and 4 independent gene conversions. The number and length of identified recombination events suggest that Arabidopsis gene conversions are likely fewer and with shorter tracts than those in yeast. In addition, the analysis of variations in offspring plants showed meiosis provided a rapid mechanism to generate copy number variations (CNVs) by reshuffling existing variations.
In the second study, a recently developed method was applied to collect Arabidopsis meiocytes, a limited number of cells undergoing meiosis, and then small RNAs were profiled using SOLiD sequencing. 97 of 266 known miRNAs show expression in meiocytes. Interestingly, five miRNAs were found to account for more than half of the total miRNA expression in meiocytes, among which miR158a takes up about one third. The target genes of these five miRNAs have little or low expression in meiocytes. One putative novel miRNA was identified, which shows conservation with rice and maize. Analysis of longer…
Advisors/Committee Members: Hong Ma, Dissertation Advisor/Co-Advisor, Stephen Wade Schaeffer, Committee Chair/Co-Chair, Gong Chen, Committee Member, Naomi S Altman, Special Member, Anton Nekrutenko, Committee Member.
Subjects/Keywords: next generation sequencing; meiotic recombination; small RNA; cortex gene expression
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Han, X. (2012). understanding gene expression and genetic recombination by next generation sequencing. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13792
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Han, Xinwei. “understanding gene expression and genetic recombination by next generation sequencing.” 2012. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/13792.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Han, Xinwei. “understanding gene expression and genetic recombination by next generation sequencing.” 2012. Web. 07 Mar 2021.
Vancouver:
Han X. understanding gene expression and genetic recombination by next generation sequencing. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/13792.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Han X. understanding gene expression and genetic recombination by next generation sequencing. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/13792
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
8.
Li, Sixing.
Application of acoustofluidic technologies in cell biology.
Degree: 2015, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/27204
► The advances in cell biology have benefited from the invention of new technologies. Over the past two decades, microfluidics has emerged as a powerful platform…
(more)
▼ The advances in cell biology have benefited from the invention of new technologies. Over the past two decades, microfluidics has emerged as a powerful platform for cell analyses and studies. In particular, acoustofluidic technologies offer some attractive features and have great application potential in cell biology and its related fields. This dissertation presents the development of acoustofluidic or microfluidic platforms that tackle some current challenges faced in cell biology. First of all, an acoustofluidic-based multichannel droplet sorter is demonstrated that can effectively sort picoliter droplets into multiple outputs. The future development of a fluorescence-activated droplet sorter (FADS) can realize the screening and sorting of cells based on secreted biomarkers. Secondly, an acoustofluidic-based, automatic, and continuous-flow cell washing device is developed and its application in the transfer of inflammatory cells from human sputum samples is reported. This acoustofluidic device preserves the viability and integrity of transferred inflammatory cells and effectively removes residual dithiothreitol (DTT) utilized during sputum liquefaction to facilitate more accurate identification of inflammatory lung cells from human sputum samples. Thirdly, a cell co-culture platform is developed that can form organized cell co-culture for studying heterotypic cell-cell interactions. The study of cancer cell mobility within co-culture demonstrates its utilization as an in vitro platform for the evaluation of the invasiveness of cancer cells and anti-tumor drug screenings. At last, a single-cell virology platform is developed that enables high-throughput, real-time, and automated observation of single-cell viral infection dynamics. The model studies of poliovirus have revealed enormous stochastic behavior that likely plays out in vivo that contributes to post-infection outcomes. The single-cell level investigations of viral infections unravel the delayed replication of an attenuated poliovirus mutant and provide insight into the evolutionary dynamics of viruses under selection pressure of antiviral drugs.
Advisors/Committee Members: Jun Huang, Dissertation Advisor/Co-Advisor, Craig Eugene Cameron, Dissertation Advisor/Co-Advisor, Jun Huang, Committee Chair/Co-Chair, Craig Eugene Cameron, Committee Chair/Co-Chair, Andrea Marie Mastro, Committee Member, Gong Chen, Committee Member.
Subjects/Keywords: microfluidics; acoustofluidic; surface acoustic wave; cell biology; virology; single-cell analysis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Li, S. (2015). Application of acoustofluidic technologies in cell biology. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/27204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Li, Sixing. “Application of acoustofluidic technologies in cell biology.” 2015. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/27204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Li, Sixing. “Application of acoustofluidic technologies in cell biology.” 2015. Web. 07 Mar 2021.
Vancouver:
Li S. Application of acoustofluidic technologies in cell biology. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/27204.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Li S. Application of acoustofluidic technologies in cell biology. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/27204
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
9.
Zhou, Yijing.
Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment.
Degree: 2018, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/14925yxz167
► Schizophrenia (SCZ) is a chronic, debilitating mental disorder that affects approximately 1% of the population. The symptoms of SCZ fall into three categories: positive, negative,…
(more)
▼ Schizophrenia (SCZ) is a chronic, debilitating mental disorder that affects approximately 1% of the population. The symptoms of SCZ fall into three categories: positive, negative, and cognitive. Current understanding attributes SCZ to both genetic and environmental determinants, supported by clinical and experimental evidence. Earlier genetic studies of SCZ have focused on monogenetic factors and family studies. Entering the new millennium, genome-wide association studies (GWASs) started to be used to find the disease-associated loci on the meta-genomic scale.
Single nucleotide polymorphism (SNP) rs1344706, localized in the gene ZNF804A, was the first SNP identified to achieve genome-wide significance for psychosis. Several follow-up GWASs have validated the association of rs1344706 with SCZ and other psychosis in different populations. Although the association with SCZ has been reported since 2008, the molecular function of ZNF804A remains largely unclear.
In our study, we found that ZFP804A (the rodent homolog of ZNF804A) expression is high in the embryonic mouse brain but decreased in the adulthood. We proved that proper expression level of ZFP804A is essential for normal neuronal migration. We also noticed decreased neural progenitor cell (NPC) proliferation and differentiation caused by insufficient ZFP804A.
To unbiasedly elucidate its molecular functions, we conducted a yeast two-hybrid (Y2H) screening and identified novel proteins that interact with ZNF804A. The gene ontology (GO) enrichment analysis revealed two major functions of ZNF804A interacting proteins: cellular adhesion/cytoskeleton regulation and translation control. In sucrose gradient fractionation assay, ZNF804A co-fractionates with translational machinery and modulates the translational efficiency potentially through the mechanistic target of rapamycin (mTOR) pathway. Using Duolink® proximity ligation assay (PLA), we confirmed the interaction between ZNF804A and ribosomal protein SA (RPSA). A proper level of RPSA is critical for optimal translation efficiency. Overexpression of RPSA rescues the migration and translation defects caused by Zfp804a knockdown. On the other hand, RPSA also serves as a receptor for laminin and presence of laminin in the extracellular matrix (ECM) augments the interaction between RPSA and ZNF804A. This implies that the function of ZNF804A might be regulated by extracellular cues.
In addition, ZFP804A target RNA was identified with RNA-immunoprecipitation - RNA sequencing (RIP-seq). ZFP804A is physically associated with transcripts involved in ribosomal and mitochondrial functions. This suggests that ZFP804A might regulate translation through multiple mechanisms: direct involvement as a part of translational machinery; indirect contribution by regulating the expression level of other components of translational machinery. The role of ZNF804A in regulating translation efficiency of target transcripts is confirmed by Duolink® PLA. Among the ZNF804A bound transcripts, neurogranin (Nrgn) has been associated with SCZ in…
Advisors/Committee Members: Yingwei Mao, Dissertation Advisor/Co-Advisor, Yingwei Mao, Committee Chair/Co-Chair, Timothy J Jegla, Committee Member, Gong Chen, Committee Member, Wendy Hanna-Rose, Outside Member.
Subjects/Keywords: schizophrenia
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhou, Y. (2018). Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/14925yxz167
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhou, Yijing. “Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment.” 2018. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/14925yxz167.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhou, Yijing. “Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment.” 2018. Web. 07 Mar 2021.
Vancouver:
Zhou Y. Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment. [Internet] [Thesis]. Penn State University; 2018. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/14925yxz167.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhou Y. Interactome analysis reveals ZNF804A, a schizophrenia risk gene, as a novel component of protein translational machinery critical for embryonic neurodevelopment. [Thesis]. Penn State University; 2018. Available from: https://submit-etda.libraries.psu.edu/catalog/14925yxz167
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
10.
Wang, Shu.
Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells.
Degree: 2014, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/21302
► In cancer cells, tumor suppressor genes are frequently silenced by enzymes that catalyze epigenetic histone modifications. Peptidylarginine deiminase 4 (PAD4), an enzyme that converts Arg…
(more)
▼ In cancer cells, tumor suppressor genes are frequently silenced by enzymes that catalyze epigenetic histone modifications. Peptidylarginine deiminase 4 (PAD4), an enzyme that converts Arg or monomethyl-Arg to citrulline in histones, is markedly overexpressed in many human cancers. Previously, researchers in in our lab have found that PAD4 counteracts the function of protein arginine methyltransferase; and thus, alters the transcription status of p53 target genes, suggesting that PAD4 is a potential target for cancer treatment. Furthermore, PAD4 is expressed in neutrophils, and is essential for NET formation induced by bacteria and pro-inflammatory cytokines. In this dissertation, I will report the inhibition of the growth of cancer cells by the novel PAD inhibitors my colleagues and I generated. Among those with low micromolar IC50, YW3-56 induced p53 target gene SESN2 (sestrin 2, a negative regulator of mTOR signaling); and thus, inhibited the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in p53 wild type osteosarcoma U2OS cancer cells. In U2OS cells, PAD4 functions as a co-repressor of p53 to regulate SESN2 expression. However, YW3-56 inhibits the growth of diverse cancer cells in a p53 independent manner. In the p53 mutant breast cancer MDA-MB-231 cells, YW3-56 triggers a type of cell death distinct from apoptosis, one that shows mitochondria depletion, mTORC1 inhibition, and blocking of autophagy. I investigated the mechanism underlying the growth inhibition effect of YW3-56 in the MDA-MB-231 cells and identified ATF4, a transcription factor in the ER stress pathway, as the novel transcription regulator mediating SESN2 expression. Using YW3-56 as a query tool, I found that ATF4 WAS required for YW3-56-induced SESN2 expression. Forced expression of ATF4 was sufficient to activate SESN2. With the detection of the ATF4 binding site on SESN2 promoter region, we identified the ATF4-SESN2 transcription circuit as a novel link between the ER stress and the mTORC1 signaling pathway. Furthermore, YW3-56 treatment triggered ROS accumulation in MDA-MB-231 cells, and the YW3-56 induced ATF4 target gene expression was ROS dependent. This finding suggests that ROS might active other factors that cooperate with ATF4 for transcription regulation. In nude mice xenograft experiments, we found that YW3-56 was effective in inhibiting the growth of tumors derived from the MDA-MB-231 subline 1833TR cells. Its antitumor efficiency also correlated with the gene transcription profiling featured a significant induction of SESN2. Taken together, ATF4-SESN2 circuit could be a potential therapeutic target for p53 mutant cancers. In this thesis, I unveiled the anticancer mechanisms and therapeutic potential of the pan-PAD inhibitor YW3-56.
Advisors/Committee Members: Yanming Wang, Dissertation Advisor/Co-Advisor, Yanming Wang, Committee Chair/Co-Chair, Andrea Marie Mastro, Committee Member, David Scott Gilmour, Committee Member, Gong Chen, Committee Member, Robert Paulson, Committee Member.
Subjects/Keywords: PAD inhibitor; cancer epigenetics; ChIP-exo; citrullination; ER
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, S. (2014). Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/21302
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wang, Shu. “Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells.” 2014. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/21302.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wang, Shu. “Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells.” 2014. Web. 07 Mar 2021.
Vancouver:
Wang S. Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/21302.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wang S. Peptidylarginine deiminase inhibitors regulate autophagy of human cancer cells and inflammation response of immune cells. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/21302
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
11.
Wang, Rong.
PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.
Degree: 2014, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/21417
► Insulin synthesis and secretion, as well as cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in any of these…
(more)
▼ Insulin synthesis and secretion, as well as cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in any of these aspects leads to development of diabetes. PERK (EIF2AK3) is essential for normal development and function of the insulin-secreting β-cell. Genetic ablation of PERK in humans and mice results in permanent neonatal diabetes featuring insufficient β-cell mass, impaired insulin synthesis and ablated insulin secretion. However, previous attempts to identify the primary functions of PERK were confounded by those severe abnormalities within PERK-deficient β-cells. Here, I used a newly developed and highly specific inhibitor of PERK to determine the immediate effects of acute PERK activity inhibition. Stimulated subcellular Ca2+ signaling and insulin secretion in human and rodent β-cells was found to be rapidly reduced as a consequence of acute inhibition of PERK. These PERK-dependent dysfunctions stem from alterations in store-operated Ca2+ entry, sarcoplasmic-endoplasmic reticulum Ca2+ ATPase activity, and possibly some of the transient receptor potential channels. I also found that PERK regulates calcineurin, and pharmacological inhibition of calcineurin results in similar defects on stimulus-secretion coupling. My findings by using PERK inhibitor demonstrate that PERK acutely regulates β-cell Ca2+ signaling and insulin secretion.
In addition, I used an alternative strategy to identify the primary functions of PERK by examining mice with one copy of the loss-of function Perk mutation (Perk heterozygous mice). Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. I found that Perk heterozygous mice first exhibited elevated proinsulin synthesis, changes in ER chaperone expression, and enhanced insulin secretion during neonatal and juvenile development, followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These effects of Perk heterozygosity are opposite to what has been learned from previously studies using Perk knockout mice and therefore suggest an inverted U-shaped dose effect on insulin production and secretion with half-dosage (Perk heterozygotes) defining the maximum. Moreover, because commonly used sensitive markers for ER stress were not differentially expressed in Perk heterozygous mice, these PERK-dependent differences are not likely to entail the well-known function of PERK in ER stress response.
Taken together my thesis work suggests that PERK has two major functions in the pancreatic β-cells: 1) acutely regulating insulin secretion through modulation of Ca2+ dynamics in a calcineurin-dependent pathway; and 2) impacting proinsulin folding and quality control in a longer-term through modulation of ER chaperone expression. These two major functions of PERK coordinate with each other and influence whole-body insulin production and glucose…
Advisors/Committee Members: Douglas Cavener, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Gong Chen, Committee Member, Melissa Rolls, Committee Member.
Subjects/Keywords: PERK eIF2alpha kinase; Ca2+ dynamics; insulin secretion; insulin biosynthesis; diabetes; ER stress; beta cell proliferation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, R. (2014). PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/21417
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/21417.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Web. 07 Mar 2021.
Vancouver:
Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/21417.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/21417
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
12.
Maxson, Marc M.
Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7552
► The human brain is essentially a composite of billions of parallel information processing units. Each neuron in the brain is a unique entity defined by…
(more)
▼ The human brain is essentially a composite of billions of parallel information processing units. Each neuron in the brain is a unique entity defined by its local environment and the connections it makes with neighboring neurons. In turn, each of those neighboring neurons is somewhat different from each other due to variation in their connections, intracellular millieu, and local environments. While the notion of a billion unique processors operating in parallel sounds too daunting to fathom, much less describe scientifically, there are certain shared phenomena common to most (and possibly all) neurons. This thesis is concerned with just one of these phenomena: exocytotic plasticity.
Plasticity, or the ability of a cell to change in a manner associated with more effective functioning, is part of what makes the brain a powerful learning and memory tool. While plasticity can take many forms, this thesis is just concerned with changes in the exocytosis process, or exocytotic plasticity. Exocytosis is the process by which cells secrete molecules that affect nearby cells and transmit information in the form of chemical messages. These messengers, or neurotransmitters, are packed in small spherical membrane enclosures called vesicles that fuse with the cell membrane to release neurotransmitters in packets. In general, the exocytotic process is quite uniform between various cell types, but certain treatments can cause this process to occur with slower or faster kinetics, and many neuromodulators can cause the number of exocytotic events per unit time to change in frequency.
Constant potential amperometry is one method to monitor exocytosis from single cells in culture with sub millisecond time resolution. By placing a carbon fiber against the surface of an excitable cell, electroactive neuromotransmitters released by the cell (such as dopamine) can be quantitatively oxidized to produce a small current that is proportional to the amount secreted. Thus amperometry can produce a great deal of information pertinent to questions about exocytosis. It has been used to study regulated exocytosis both in vivo and in isolated cultures. It has revealed fine details about exocytosis before, during, and immediately following vesicle fusion. It can reveal net changes in release as a form of toxological assay or intracellular signal screen. In addition, the amount released from a single fusion event or quantal size can be manipulated by treatments. These manipulations have provided evidence that cells could also manipulate the exocytosis process as a form of exocytotic plasticity.
One such manipulation, a collaboration with Yoshiko Niimura, demonstrates the effects of increasing various types of phospholipids on exocytosis. When cells are incubated with phosphatidylcholine (PC), phosphatidylethanolamine (PE), or sphingomyelin (SM), changes in the quantal size and/or vesicle fusion kinetics are observed. PC slowed and PE accelerated the expulsion of neurotransmitter from vesicles. Phosphatidylserine (PS) increased the number of…
Advisors/Committee Members: Andrew Ewing, Committee Chair/Co-Chair, Kyung An Han, Committee Member, Gong Chen, Committee Member, Nandini Vasudevan, Committee Member.
Subjects/Keywords: hypertonic; osmolarity; store-operated; voltage-gated; calcium; neuromodulator; estrogen; secretion; exocytosis; neuroscience; L-DOPA; phosphatidylserine; phosphatidylethanolamine; phosphatidylcholine
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Maxson, M. M. (2008). Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7552
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Maxson, Marc M. “Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7552.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Maxson, Marc M. “Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
.” 2008. Web. 07 Mar 2021.
Vancouver:
Maxson MM. Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7552.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Maxson MM. Modulation of exocytosis by estrogen, altered membrane composition, and osmolarity
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7552
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
13.
Zhang, Wei.
FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7599
► PERK eIF2-alpha kinase is an ER transmembrane protein sensing ER stress and [Ca2+]ER alteration under physiological or pharmacological condition. When large scale of eIF2-alpha is…
(more)
▼ PERK eIF2-alpha kinase is an ER transmembrane protein sensing ER stress and [Ca2+]ER alteration under physiological or pharmacological condition. When large scale of eIF2-alpha is phosphorylated, global translation is repressed to alleviate ER stress; while moderate eIF2-alpha level may selectively induce a subgroup of gene expression. PERK is highly expressed in secretory cells such as pancreatic Beta-cells, which have elaborate network of ER and high protein load in the ER. Thus PERK is widely speculated to alleviate ER overload or stress and preserve exquisite ER function in those cells in particular.
Genetic deletion of PERK in mice causes early onset of diabetes and other disorders, mirroring Wolcott Rallison Syndrome in human. Our lab demonstrated that Beta-cell hypoplasia and dysfunction contribute to hyperglycemia in PERK null mutant mice. Immunofluorescent assay revealed that disrupted proliferation and neogenesis rather than apoptosis cause Beta-cell hypoplasia, which disproves the popular perception that excessive Beta-cell death under ER stress being the main reason. Molecular evidence indicated that Beta-cell is trapped in G2 or late G1/S phase of cell cycle, while we failed to see the reduction of cyclin D and cdk4. Cyclin D and cdk4 was stated to be dispensable for Beta-cell duplication in the early developmental stage. The Proliferation defects since fetal stage, together with neogenesis degeneration illustrate impeded Beta-cell development. We speculate that maternal factors such as glucose may regulate Beta-cell proliferation and neogenesis via PERK, which will be exploited. For Beta-cell function, glucose stimulated insulin secretion is compromised in Perk -/- islets; Beta-cell marker, such as insulin, MafA and Pdx1 are downregulated. In addition, insulin and GLUT2 are accumulated in distended ER, suggesting general ER dysfunction. ER stress markers, Bip, spliced Xbp1 and Chop are not induced. Thus, via eIF2-alpha substrate, PERK either directly or indirectly affect the development, expansion and function of Beta-cells. The mechanism is still under investigation, however it is not along ER stress induced canonical unfold protein response (UPR) pathway. Study of tissue specific knockout mice, including pcPKO, enPKO, BetaPKO, exPKO mice, and Beta-PERK:PKO mice (Perk transgenic mice) suggest deteriorated Beta-cells are cell autonomous effect.
Advisors/Committee Members: Douglas Cavener, Committee Member, Richard W Ordway, Committee Chair/Co-Chair, Pamela Hankey Giblin, Committee Member, Gong Chen, Committee Member.
Subjects/Keywords: ER stress; PERK; eIF2-alpha; Beta-cell; hypoplasia
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, W. (2008). FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7599
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhang, Wei. “FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7599.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhang, Wei. “FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
.” 2008. Web. 07 Mar 2021.
Vancouver:
Zhang W. FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7599.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhang W. FUNCTIONS OF PERK eIF2-alpha KINASE IN THE MOUSE PANCREATIC Beta-CELLS
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7599
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
14.
Jiang, Min.
FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8546
► Endocytosis plays a fundamental role in regulating cell signaling, protein and lipid trafficking, and uptake of nutrients and pathogens in all eukaryotic cells. In astrocytes,…
(more)
▼ Endocytosis plays a fundamental role in regulating cell signaling, protein and lipid trafficking, and uptake of nutrients and pathogens in all eukaryotic cells. In astrocytes, endocytosis is particularly important for the uptake of nutrients. However, the molecular mechanisms underlying astroglial endocytosis are poorly understood. Using live fluorescence imaging with FM dye, we identify a rapid and constitutive endocytosis mechanism in cultured astrocytes. The endocytic uptake of FM dye is much faster than that of transferrin and the internalized FM dye is not colocalized with clathrin, indicating a clathrin-independent endocytic pathway. Moreover, this rapid endocytosis is caveolae-independent as indicated by intact FM dye uptake after blocking caveolae formation and lack of colocalization of FM puncta and caveolin.
In addition, rapid endocytosis is independent of dynamin but potently regulated by the early endosomal protein Rab5. After being internalized, FM dye is quickly sorted through early endosomes and transported to lysosomes. Interestingly, this rapid form of endocytosis is substantially regulated by intracellular Ca2+. The neural and gliotransmitters ATP and glutamate induce an increase of intracellular Ca2+ in astrocytes, which greatly enhances rapid endocytosis. Furthermore, ATP is internalized through the same endocytic pathway as FM dye. This suggests a potential feedback control of the ATP signaling pathway in astrocytes. Moreover, amyloid beta peptide also significantly increases the rapid endocytosis through increasing intracellular Ca2+ in astrocytes. These results suggest that astroglial cells posess a unique endocytic pathway that is independent of clathrin and dynamin but tightly regulated by intracellular Ca2+ in response to physiological and pathological stimuli.
Advisors/Committee Members: Gong Chen, Committee Member, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Andrew Ewing, Committee Member, Matthew Whim, Committee Member.
Subjects/Keywords: astrocytes; endocytosis; clathrin
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Jiang, M. (2008). FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8546
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Jiang, Min. “FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/8546.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Jiang, Min. “FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
.” 2008. Web. 07 Mar 2021.
Vancouver:
Jiang M. FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/8546.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Jiang M. FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8546
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
15.
Edathil, Jocelyn P.
DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8882
► RNA viruses cause a plethora of diseases which are difficult to treat due to the high mutation rate of such pathogens. Current therapies for RNA…
(more)
▼ RNA viruses cause a plethora of diseases which are difficult to treat due to the high mutation rate of such pathogens. Current therapies for RNA virus infections are severely limited due to the development of antiviral drug resistance. Such viruses exist in nature as a quasispecies resulting from the high error frequency of replication. RNA viruses as thus highly adaptable and also exist on the edge of “error catastrophe.” Thus small increases in the mutation rate can cause a drastic decrease in viral viability. Based on this concept, a new approach to the design of antiviral agents termed “lethal mutagenesis” has emerged whereby drugs that increase the error rate of RNA viruses may be developed to combat viral diseases.
Chapter one provides an overall review of lethal mutagenesis as an antiviral strategy. Ribavirin, a clinically utilized nucleoside antiviral agent, has shown to be a lethal mutagen. Once transported across cellular membranes and phosphorylated to the 5΄ triphosphate, the base-modified nucleoside triphosphate is a degenerate substrate for the viral RNA-dependent RNA polymerase (RdRP). In the viral genome, misincorporation is templated by the ribavirin pseudo base resulting in an increase in overall frequency of mutations and error catastrophe and decreased infectivity of the virus.
The work described herein explores the efforts to design and synthesize effective antiviral nucleosides and probe their mechanism of action as lethal mutagens. Chapter two describes the investigation of isocarbostyril nucleosides as antiviral agents. Three isocarbostyril ribonucleoside analogs, ICS-R, MICS-R, and SICS-R, were synthesized by the Vorbrüggen procedure and evaluated as antivirals. ICS-R was discovered to be the most potent analog followed by SICS-R and MICS-R demonstrating antiviral activity greater than clinical agent Ribavirin against poliovirus. Additionally, 5΄ and 2΄ modified ICS-R control compounds demonstrated no antiviral effect. The corresponding ICS-R analog triphosphates displayed slow kinetics of incorporation and revealed inhibition of PV viral RdRP as the mode of action. ICS-R(TP) accumulated intracellularly to a greater degree than MICS-R and SICS-R corroborating antiviral and biochemical results.
Chapter three is divided into two sections exploring the mechanism of action of 5-nitroindole nucleoside and the development of 5-halo indole nucleosides. The mechanism of antiviral activity of 5-nitroindole ribonucleoside was investigated though the evaluation of a series of mechanistic probes and biochemical characterization of phosphorylated 5-nitroindole analogs. 5NINDN(DP) and 5NINDN(MP) were synthesized and evaluated as inhibitors of PV viral polymerase in comparison with 5NINDN(TP) and the parent nucleoside 5NINDN. Surprisingly, both triphosphate and diphosphate inhibited the viral polymerase, however reversed-phase HPLC analyses revealed detectable phosphorylation limited only to 5NINDN(MP). Further evaluation of mechanistic probes 5΄OMe5NINDN, 5-nitroindole, and…
Advisors/Committee Members: Blake R Peterson, Committee Chair/Co-Chair, Gong Chen, Committee Member, Craig Eugene Cameron, Committee Member, Anthony Edward Pegg, Committee Member.
Subjects/Keywords: nucleotides; universal base; poliovirus; lethal mutagenesis; nucleoside synthesis; RNA virus; nucleosides; RNA-dependent RNA polymerase; carbohydrate synthesis; nucleoside phosphorylation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Edathil, J. P. (2008). DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8882
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Edathil, Jocelyn P. “DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/8882.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Edathil, Jocelyn P. “DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
.” 2008. Web. 07 Mar 2021.
Vancouver:
Edathil JP. DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/8882.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Edathil JP. DESIGN, SYNTHESIS, ANTIVIRAL EVALUATION AND
METABOLISM OF
NUCLEOSIDE ANALOGS
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8882
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
16.
Clayton, William B.
STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8484
► Streptorubin B is a member of the prodigiosin family of natural products which are receiving considerable attention from academia as well as the pharmaceutical industry…
(more)
▼ Streptorubin B is a
member of the prodigiosin family of natural products which are receiving considerable attention from academia as well as the pharmaceutical industry for their novel immunosuppressive and cytotoxic properties. Despite this interest, little effort has been shown toward an asymmetric synthesis of streptorubin B or the relationship between its chirality and biological activity. Progress toward the asymmetric synthesis of streptorubin B and its stereoisomers is herein described.
Alkynyliodonium salts are versatile substrates which have been used to form a variety of heterocycles and other ring systems. The alkylidenecarbenes generated from the addition of soft nucleophiles to alkynyliodonium salts can insert intramolecularly into carbon-hydrogen bonds and typically do so with a high degree of regio- and stereoselectivity. The C ring of streptorubin B was made using this branch of hypervalent iodine chemistry, but this route was later abandoned due to failure of subsequent steps and instability of the products formed.
The challenges involved in forming medium sized rings with ring closing metathesis are beginning to be understood and in many cases have been overcome by conformation constraints. The possibility of using ring closing metathesis to close the bridging ten membered D ring of streptorubin B was explored. However, the enthalpy and entropy barriers for this conversion were determined to be too great to surmount. After other ring closing methods were investigated, a Nozaki-Hiyama-Kishi coupling was found to be successful.
Advisors/Committee Members: Ken S Feldman, Committee Chair/Co-Chair, Gong Chen, Committee Member, Scott T Phillips, Committee Member, Ronald Hedden, Committee Member, Ayusman Sen, Committee Member.
Subjects/Keywords: streptorubin; iodonium salts; metathesis
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Clayton, W. B. (2008). STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Clayton, William B. “STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/8484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Clayton, William B. “STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
.” 2008. Web. 07 Mar 2021.
Vancouver:
Clayton WB. STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/8484.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Clayton WB. STUDIES TOWARD THE TOTAL SYNTHESIS OF
STREPTORUBIN B
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8484
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
17.
Wang, Linli.
COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
.
Degree: 2009, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/10256
► Intracellular recording shows HVCRA neurons in songbirds have strong selective response to the bird’s own song. This selectivity is especially sensitive to the sequential order…
(more)
▼ Intracellular recording shows HVCRA neurons in songbirds have strong selective response to the bird’s own song. This selectivity is especially sensitive to the sequential order of the syllables spanning over several hundred milliseconds. The firing pattern of HVCRA is sparse in the sense that each HVCRA neuron only fires at most once during one motif and has such precise timing that it always gives a burst of spikes lasting around 10 ms. Developed from a song production model using synfire chains, we incorporate the sensory input into the spike propagation process by coincident detection of sensory input from upstream and lateral input inside the synfire chain. The specific wiring structure from sensory input to the synfire chain embeds the sensory sequence which can be recognized by our model. This specific structure can be learned from initial all-to-all weak connections with a postsynaptic voltage dependent learning mechanism. The stability of this model is shown by the robust performances of both recognition and learning under different synaptic noises and various defects in training sequence. In order to handle repetitive inputs, Potassium A-current is induced into our model to check the current surge due to repetitive inputs. The working region and its effect on the sequence recognition of A-current are investigated and its limited role on the single compartment model is concluded. In order to construct a more biological model and leave more room for A-current, the two-compartment model of a single HVCRA neuron replaces the single compartment model of the integrate-fire neuron. A more popular learning mechanism (spike-timing dependent plasticity) is applied to induce the specific wiring from sensory neurons to synfire chain neurons. The sequence recognition and learning of this revised network are studied. The enhanced robustness is partly due to the enlargement of the coincident region by A-current.
Advisors/Committee Members: Dezhe Jin, Dissertation Advisor/Co-Advisor, Dezhe Jin, Committee Chair/Co-Chair, John C Collins, Committee Member, Gong Chen, Committee Member, Jayanth R Banavar, Committee Member.
Subjects/Keywords: computational; songbird; HVC; sequence; recognition; learning
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wang, L. (2009). COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10256
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wang, Linli. “COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
.” 2009. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/10256.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wang, Linli. “COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
.” 2009. Web. 07 Mar 2021.
Vancouver:
Wang L. COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
. [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/10256.
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. COMPUTATIONAL STUDY ON SENSORY MOTOR INTEGRATION AND SENSORY SEQUENCE LEARNING IN SONGBIRD HVC
. [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/10256
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
18.
Wei, Xiaomu.
Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7888
► The number of cells in an organism is determined by the number of cells generated as a result of cell proliferation as well the number…
(more)
▼ The number of cells in an organism is determined by the number of cells generated as a result of cell proliferation as well the number of cells that are eliminated by cell death. Both cell proliferation and cell death are strictly regulated by developmental mechanism to ensure that an organ of a characteristic shape and size is generated. Mechanisms that regulate normal growth and cell proliferation are often perturbed in cancers. Mutational events found in cancers can either promote growth and cell proliferation or impede cell death. Our laboratory has discovered a novel tumor suppressor in Drosophila that we named mats (Mob as a tumor suppressor) which is capable of regulating both cell proliferation and cell death in a coordinated manner. Loss of Mats function results in increased cell proliferation, impaired apoptosis, and tumor formation characterized by elevated levels of the cell cycle regulator cyclin E and apoptosis inhibitor DIAP1. A human homolog of mats can rescue the lethality associated with loss of Mats function in Drosophila. Importantly, loss-of-function mutation in Mats1 have been identified in a human skin cancer and a mouse breast tumor, suggesting that mammalian mats genes may indeed act as tumor suppressors. The work described here focus on elucidating mechanisms by which Mats protein function as tumor suppressor. I provide biochemical evidence to demonstrate that Mats is a key component in the Hpo-Sav-Wts tumor suppression pathway. Hpo, Mats and Wts interact physically and functionally. Mats phosphorylation by Hpo is critical for Mats to activate Wts kinase. My research objective is to elucidate how exactly these proteins cooperate to form a signaling module, and how they are regulated at a molecular level.
Advisors/Committee Members: Richard W Ordway, Committee Chair/Co-Chair, Zhi Chun Lai, Committee Member, Douglas Cavener, Committee Member, Gong Chen, Committee Member, Wendy Hanna Rose, Committee Member.
Subjects/Keywords: hippo; growth inhibition and tumor suppression; Drosophila; mats; warts
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wei, X. (2008). Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7888
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wei, Xiaomu. “Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7888.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wei, Xiaomu. “Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
.” 2008. Web. 07 Mar 2021.
Vancouver:
Wei X. Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7888.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wei X. Control of Cell Proliferation and Apoptosis by Mob as Tumor Suppressor Protein
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7888
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
19.
Yuan, Xu.
STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7839
► ABSTRACT Inhibitory synaptic transmission in the brain is mainly mediated by heteropentameric GABAA receptors (GABAARs) composed of ƒÑ and ƒÒ subunits together with the ƒ×2…
(more)
▼ ABSTRACT
Inhibitory synaptic transmission in the brain is mainly mediated by heteropentameric GABAA receptors (GABAARs) composed of ƒÑ and ƒÒ subunits together with the ƒ×2 subunit. The postsynaptic clustering of these receptors is critical for the efficacy of synaptic transmission. Moreover, trafficking and targeting of GABAARs to the postsynaptic membrane is highly regulated, and this mechanism is thought to contribute to functional plasticity of GABAergic synapses.
The ƒ×2 subunit contributes to the majority of GABAAR subtypes and is essential for clustering of GABAARs at postsynaptic sites, for recruitment of the submembrane scaffold protein gephyrin to postsynaptic sites, and for postsynaptic function of GABAergic synapses. Targeted deletion of the ƒ×2 subunit gene leads to loss of major postsynaptic GABAAR subtypes in vivo (Essrich et al., 1998; Schweizer et al., 2003). And the fourth transmembrane region (TM4) of the ƒ×2 subunit is thought to play an important role in this mechanism (Alldred et al., 2005).
To elucidate the mechanism by which the ƒ×2 subunit contributes to trafficking of GABAARs, a yeast two hybrid screen was performed to identify novel proteins that interact with the TM4 and cytoplasmic region of the ƒ×2 subunit. As part of my Ph. D. thesis I here report the isolation of calcium-modulating cyclophilin ligand (CAML) as a novel GABAA receptor-interacting protein. CAML is an integral membrane protein first identified as endogenous ligand for cyclophilin B, the receptor of the immunosuppressant cyclosporin A (Bram and Crabtree, 1994) and subsequently shown to be essential for the endocytic recycling of internalized epidermal growth factor receptors (EGFRs) to the plasma membrane (Tran et al., 2003). Using yeast two-hybrid tests the ƒ×2 subunit-interaction domain has been mapped to the N-terminal cytoplasmic domain of CAML. Conversely, both the 3¡¦ half of the major cytoplasmic loop domain and the TM4 domain of the ƒ×2 subunit were required for interaction with CAML. This novel interaction between CAML and the ƒ×2 subunit was verified by colocalization assays and immunoprecipitations in heterologous cells, by colocalization of transfected and endogenous proteins in neurons and by co-immunoprecipitation of native proteins from brain extracts.
The role of CAML in trafficking and clustering of postsynaptic GABAAR subtypes was analyzed by disrupting the function of CAML through RNA interference (RNAi) in cultured neurons and by conditional knock-out of a floxed CAML gene in cultured neurons and mice. Following knockdown of CAML by short hairpin RNA (shRNA) based RNAi, postsynaptic clusters of GABAARs were decreased concurrent with a similar reduction in immunoreactivity representing GABAergic presynaptic terminals. Inactivation of the CAML gene in mouse embryos (Emx1Cre x CAMLf/-) resulted in neonatal lethality and neurons cultured from corresponding embryos died in vitro. Postnatal deletion of CAML in CaMKIICre2834 x CAMLf/- mice resulted in loss of ƒ×2 subunit-containing GABAARs as indicated…
Advisors/Committee Members: Richard W Ordway, Committee Chair/Co-Chair, Bernhard Luscher, Committee Member, Gong Chen, Committee Member, Douglas Cavener, Committee Member, Pamela Hankey Giblin, Committee Member.
Subjects/Keywords: calcium modulating cyclophilin ligand; trafficking; GABA-A receptor
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Yuan, X. (2008). STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7839
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yuan, Xu. “STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7839.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yuan, Xu. “STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
.” 2008. Web. 07 Mar 2021.
Vancouver:
Yuan X. STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7839.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yuan X. STRUCTURAL AND FUNCTIONAL ANALYSES OF A NOVEL INTERACTION BETWEEN GABA-A RECEPTORS AND CAML
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7839
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
20.
LI, YULIN.
The growth retardation and liver dysfunction of PERK knockout mice.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7744
► Mutations of PKR-like Endoplasmic Reticulum Kinase (PERK) eIF2alpha kinase cause multiple phenotypes in both human and mice. Perk mutations in human result in Wolcott- Rallison…
(more)
▼ Mutations of PKR-like Endoplasmic Reticulum Kinase (PERK) eIF2alpha kinase cause
multiple phenotypes in both human and mice. Perk mutations in human result in Wolcott-
Rallison syndrome. The human patients had neonatal diabetes, osteoporosis and growth
retardation. However, according to clinical observations, most of the Wolcott-Rallison
syndrome patients also had recurrent liver dysfunction/failure and they died from liver
dysfunction instead of diabetes and osteoporosis.
I used the Perk-/- mice to study the growth retardation of the mice and found out that
Insulin-Like Growth Factor I (IGF-I) was closely correlated with the body weight of both
wild type and knockout mice. The serum IGF-I reduction in Perk-/- mice was due to
reduced IGF-I mRNA level in liver. Injection of recombinant IGF-I in neonatal Perk-/-
mice partially rescued their growth retardation, suggesting that the IGF-I was important
for their growth retardation. The IGF-I changes were also correlated with the
development of liver dysfunction in Perk-/- mice. In the neonatal Perk-/- mouse liver,
where the dramatic reduction of IGF-I level was found, I also observed severe fat
accumulation, increased glycogen storage and other mild pathological changes.
I further tested whether this liver dysfunction was a hepatocyte cell autonomous defect
using both liver specific Perk conditional knockout mouse models and liver specific Perk
transgenic mouse model. With the liver specific Cre expression, I was able to obtain
considerable Perk gene deletion in neonatal mouse liver, but no phenotype was observed.
In addition to the liver specific conditional knockout mice models, I also constructed a
liver specific Perk transgenic mouse model and was able to confirm the expression of
functional Perk in the mice but it failed to rescue the growth retardation and liver
dysfunction in the global Perk-/- mice. Taken together, these results suggest that the
growth retardation and liver dysfunction in the Perk-/- mice may not be a cell
autonomous defect of hepatocytes. Moreover, our data suggest that the Perk-/- liver
dysfunction closely resembles the metabolic syndrome seen in protein energy
malnutrition.
Advisors/Committee Members: Douglas Cavener, Committee Member, Gong Chen, Committee Member, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Robert Paulson, Committee Member.
Subjects/Keywords: PERK; Liver dysfunction; Steatosis; Wolcott-Rallison syndrome; growth retardation; EIF2AK3
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
LI, Y. (2008). The growth retardation and liver dysfunction of PERK knockout mice. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7744
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
LI, YULIN. “The growth retardation and liver dysfunction of PERK knockout mice.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7744.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
LI, YULIN. “The growth retardation and liver dysfunction of PERK knockout mice.” 2008. Web. 07 Mar 2021.
Vancouver:
LI Y. The growth retardation and liver dysfunction of PERK knockout mice. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7744.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
LI Y. The growth retardation and liver dysfunction of PERK knockout mice. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7744
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
21.
Fang, Cheng.
Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7584
► GABAA receptors (GABAARs) mediate most of the fast inhibitory neurotransmission in the central nervous system. Clustering of GABAARs at postsynaptic sites is critical for the…
(more)
▼ GABAA receptors (GABAARs) mediate most of the fast inhibitory neurotransmission in the central nervous system. Clustering of GABAARs at postsynaptic sites is critical for the function of inhibitory synapses. Moreover, changes in synaptic receptor concentration are believed to contribute to functional plasticity of neurons. GABAARs are important for normal brain function as evidenced by their critical role in a wide range of neurological and neuropsychiatric diseases including epilepsy, anxiety, drug addiction, and diverse forms of mental retardation. Furthermore, GABAARs are a major site of action of clinically relevant CNS drugs, including the benzodiazepines, barbiturates, general anesthetics, and ethanol, as well as endogenous neurosteroids.
Structurally, GABAARs represent heteropentameric ligand-gated Cl- channels, typically composed of 2?, 2? and 1?2 subunit. The ?2 subunit is specifically required for proper trafficking and clustering of the major subset of GABAARs that function at inhibitory synapses. GABAARs are subject to many posttranslational modifications, including palmitoylation, phosphorylation and ubiquitination. Of particular relevance for this thesis, palmitoylation is implicated in regulated trafficking of the ?2 subunit containing GABAARs to the plasma membrane and, by extension, in synaptic plasticity of inhibitory synapses. The ?2 subunit of GABAARs is palmitoylated at multiple Cys residues in the cytoplasmic loop region. Furthermore, GODZ has recently been isolated as a ?2 subunit interacting protein that can palmitoylate the ?2 subunit in vitro.
The main objective of this doctoral thesis was to address the function of GODZ-mediated palmitoylation of the ?2 subunit in neurons. Here, I have shown that GODZ and its close paralog, SERZ-?, are the only enzymes among 23 DHHC family members of palmitoyl acyltransferases (PATs) that exhibit significant palmitoyltransferase activity for the ?2 subunit as a substrate in vitro. Moreover, GODZ and SERZ-? show indistinguishable expression patterns in brain as well as palmitoylation-dependent interaction with the ?2 subunit. Moreover, they form homo- and heteromultimers on expression in heterologous cells. Analyses in neurons indicate that GODZ is critically important for trafficking of GABAARs to synapses, for whole cell GABAergic inhibitory function and for normal amplitude and frequency of GABAergic miniature inhibitory synaptic currents. Indirectly, GODZ mediated palmitoylation in postsynaptic neurons is required for presynaptic GABAergic innervation. In contrast, GODZ is dispensable for AMPA receptor-mediated whole cell currents as well as miniature excitatory postsynaptic currents. Thus, GODZ-mediated palmitoylation of GABAARs is important selectively for structural and functional plasticity of inhibitory synapses.
Advisors/Committee Members: Bernhard Luscher, Committee Chair/Co-Chair, Douglas Cavener, Committee Member, Gong Chen, Committee Member, Erin Elizabeth Sheets, Committee Member, Wendy Hanna Rose, Committee Member.
Subjects/Keywords: trafficking; synaptogenesis; inhibitory synapses; palmitoylation; GABAA receptors; DHHC-CRD proteins
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Fang, C. (2008). Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7584
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Fang, Cheng. “Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7584.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Fang, Cheng. “Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
.” 2008. Web. 07 Mar 2021.
Vancouver:
Fang C. Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7584.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Fang C. Structural and Functional Modulation of Inhibitory Synapses by GODZ-mediated Palmitoylation of GABAA Receptors
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7584
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
22.
Zou, Beiyan.
A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/7850
► Synaptic transmission is a fundamental aspect of neural function. This process typically occurs at chemical synapses, where presynaptic release of chemical neurotransmitters leads to excitation…
(more)
▼ Synaptic transmission is a fundamental aspect of neural function. This process typically occurs at chemical synapses, where presynaptic release of chemical neurotransmitters leads to excitation or inhibition of the postsynaptic cell. Neurotransmitter release is triggered by calcium influx through presynaptic voltage-gated calcium channels. In Drosophila, the molecular basis of presynaptic calcium channel function has been defined through our analysis of a temperature-sensitive (TS) paralytic mutant of the calcium channel alpha1 subunit gene, cacophony (cac). This mutant, referred to as cacTS2, has also served as a starting point for further genetic analysis. To broaden our understanding of the functions and interactions of cac-encoded calcium channels, we have conducted a screen for genetic modifiers of cacTS2. Of ten mutations recovered, four were intragenic and six were extragenic. Analysis of intragenic modifiers has broadened our understanding of intramolecular interactions within the calcium channel alpha1 subunit.
Here we report characterization of three extragenic enhancers of cacTS2, which map to a single locus designated as e(cac)A. Genetic analysis, sequencing analysis, complementation tests, immunoblotting and immunocytochemistry have shown that e(cac)A is futsch, the homolog of microtubule-associated protein 1 (MAP1) in Drosophila. Electrophysiological analysis of synaptic transmission has revealed that futsch mutations enhance the synaptic phenotype of cacTS2. Furthermore, immunocytochemical analysis indicates that the localization of presynaptic calcium channels, microtubules and actin as well as the distribution of synaptic vesicles is normal in futsch mutants, suggesting a role for dMAP1/FUTSCH in synaptic function. Accordingly, dMAP1/FUTSCH exhibits a punctate distribution along microtubules within presynaptic boutons and extending to active zones. Taken together, our findings have implicated novel molecular mechanisms of synaptic transmission, in which a specialized form of presynaptic microtubule-based cytoskeleton may function in synaptic transmission through interactions with presynaptic calcium channels.
A part of this work has revealed posttranslational proteolytic processing of a dMAP1/FUTSCH protein precursor as demonstrated previously for mammalian MAP1s. A ~20kD fragment of dMAP1/FUTSCH was specifically detected using a newly developed anti-LCf antibody and this was shown to be a dMAP1/FUTSCH light chain by colocalization with the heavy chain at the neuromuscular synapses and co-immunoprecipitation of the heavy and light chains. These findings demonstrated a structural conservation among MAP1 proteins. Further molecular and functional characterization is expected to define the in vivo roles of MAP1 in synaptic transmission and the underlying mechanisms.
Advisors/Committee Members: Douglas Cavener, Committee Chair/Co-Chair, Gong Chen, Committee Member, Kyung An Han, Committee Member, Zhi Chun Lai, Committee Member, Richard W Ordway, Committee Member.
Subjects/Keywords: synaptic transmission; MAP1; presynaptic calcium channel; cacophony; futsch; Drosophila
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zou, B. (2008). A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7850
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zou, Beiyan. “A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/7850.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zou, Beiyan. “A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.” 2008. Web. 07 Mar 2021.
Vancouver:
Zou B. A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/7850.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zou B. A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7850
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
23.
Sun, Qi.
ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8929
► In the past decade, our group has developed a novel technology that can be used to dramatically enhance uptake of cell impermeable macromolecules by mammalian…
(more)
▼ In the past decade, our group has developed a novel technology that can be used to dramatically enhance uptake of cell impermeable macromolecules by mammalian cells. By mimicking small natural cell surface receptors, synthetic receptors, composed of N-alkyl-3â-cholesterylamine membrane anchors linked to protein-binding motifs, can be installed on cell surfaces. Mechanistic studies
have revealed that similar to certain natural cell surface receptors, the synthetic receptors internalize cargo molecules through a clathrin-mediated endocytic pathway. However, the lack of an efficient method for the synthesis of 3â-
cholesterylamine has limited the development of this technology. Additionally, trapping of molecules delivered by synthetic receptors in confined intracellular compartments, endosomes, restricts potential applications of this delivery system. To address these issues, we developed novel and practical methodologies for the large-scale preparation of 3â-cholesterylamine and related building blocks; we also designed and synthesized novel 3â-cholesterylamine-capped PC4 lytic peptides, which enable 3â-cholesterylamine-conjugated cargo bearing a disulfide linkage to selectively escape from early/recycling endosomes of living mammalian cells. Furthermore, study of the interactions of C-reactive protein with
phosphocholine-containing synthetic receptors led us to the discovery of a novel method to promote apoptosis in Jurkat lymphocytes.
The other area of my research focused on the development of novel methodologies for the preparation of antiviral agents and their phosphoylated metabolites. A novel one-pot approach for the synthesis of nucleoside 5’-
triphosphates from nucleoside 5’-H-phosphonate monoesters was explored. We demonstrated that fully deprotected 5’-H-phosphonates of antiviral nucleosides can be converted via pyridinium phosphoramidate intermediates to the corresponding 5’-triphosphate products, which can be readily purified using a two-step purification protocol. We also constructed a small 39-
member library based on a vinylbenzimidazolium Akt inhibitor through the discovery of a novel and efficient Zr(IV)-catalyzed cyclization of substituted 1,2-arylenediamines and á,â-unsaturated aldehydes.Biological screening of the new compound library identifed four compounds with greater antiviral activity than the lead compound.
Advisors/Committee Members: Joseph M Bollinger Jr., Dissertation Advisor/Co-Advisor, Joseph M Bollinger Jr., Committee Chair/Co-Chair, Professor Blake R Peterson, Committee Chair/Co-Chair, Avery August, Committee Member, Gong Chen, Committee Member.
Subjects/Keywords: nucleoside triphosphate; cholesterylamine; synthetic receptors; endosome disruption
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, Q. (2008). ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8929
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sun, Qi. “ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/8929.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sun, Qi. “ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS.” 2008. Web. 07 Mar 2021.
Vancouver:
Sun Q. ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/8929.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sun Q. ADVANCES IN SYNTHESIS AND APPLICATIONS OF ARTIFICIAL CELL SURFACE RECEPTORS AND METHODOLOGY FOR PREPARATION OF
NOVEL ANTIVIRAL AGENTS. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8929
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
24.
Murakami, Shoko.
ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/8917
► Type A GABA receptors (GABAARs) are the major sites of fast synaptic inhibition in the central nervous system (CNS) and mediate the therapeutic effects of…
(more)
▼ Type A GABA receptors (GABAARs) are the major sites of fast synaptic inhibition in the central nervous system (CNS) and mediate the therapeutic effects of many clinically important drugs. The efficacy of synaptic inhibition is critically dependent on the postsynaptic accumulation of GABAARs. Golgi-specific DHHC zinc finger protein (GODZ; aka, DHHC3) and SERZ-beta (aka, DHHC7) have been identified as palmitoyl acyl-transferases (PATs) of the gamma2 subunit of GABAARs. In addition, the cell adhesion molecule neuroligin 2 (NL2) is localized at GABAergic synapses and implicated in GABAergic synapse formation. Previous analyses of GODZ by RNAi in cultured neurons had suggested that they are important for postsynaptic accumulation of GABAARs at inhibitory synapses. In addition these studies pointed to a novel possible role of GABAARs in the assembly of GABAergic inhibitory synapses.
A first objective of this doctoral thesis was to elucidate the function of GODZ and SERZ-beta in vivo. In order to achieve this purpose, global and conditional knock-out (KO) mice were generated for both GODZ and SERZ-beta. Genetic deletion of GODZ and SERZ-beta was confirmed by genomic Southern blotting, RT-PCR and immunofluorescence analyses. Global GODZ and SERZ-beta KO mice were found to be viable, whereas GODZ and SERZ-beta double knock-out (DKO) mice showed a partially penetrant perinatally lethal phenotype. Male, but not female, GODZ KO mice exhibited a small but significant reduction in body weight compared to wild type (WT) littermate controls. A more dramatic reduction in body weight was evident in DKO mice, as quantified in females but also overtly evident in males. Compared to WT littermate controls, GODZ KO mice showed complex behavioral alterations characterized by excessive jumping in response to handling, hindleg clenching upon suspension by their tail, hyperlocomotion in an Open Field test, as well as enhanced Prepulse Inhibition of acoustic startle responses. However, GODZ KOs showed normal anxiety related behavior in Free Choice and Elevated Plus Maze tests. Immunofluorescence analyses of cortical neuron cultures prepared from GODZ KO or GODZ/SERZ-beta DKO mice revealed unaltered numbers of postsynaptic clusters of gamma2 subunit containing GABAARs and the inhibitory postsynaptic scaffold protein gephyrin. Similarly, the number of clusters of the corresponding presynaptic marker glutamate decarboxylase (GAD) and vesicular inhibitory amino acid transporter (VIATT) were also unchanged. Consistent with unaltered clustering in pure DKO cultures, the surface expression levels of the gamma2 subunit and NL2 assessed by biotinylation was unaltered in DKO compared to WT cultures. However, when mutant neurons were co-cultured with an excess of WT neurons, punctate staining for postsynaptic GABAAR clusters and presynaptic inhibitory synaptic markers of GODZ KO and DKO neurons was dramatically reduced compared to neurons of pure WT cultures. Similarly, gamma2 subunit heterozygous neurons co-cultured with an excess of WT neurons showed a…
Advisors/Committee Members: Bernhard Luscher, Dissertation Advisor/Co-Advisor, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Robert Paulson, Committee Member, Gong Chen, Committee Member, Erin Elizabeth Sheets, Committee Member.
Subjects/Keywords: knock out; trafficking; Neuroligin 2; GABAA receptor; palmitoylation
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Murakami, S. (2008). ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8917
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Murakami, Shoko. “ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/8917.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Murakami, Shoko. “ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
.” 2008. Web. 07 Mar 2021.
Vancouver:
Murakami S. ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/8917.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Murakami S. ANALYSES OF THE FUNCTION OF THE PALMITOYL TRANSFERASES GODZ AND SERZ-BETA IN KNOCK-OUT MICE
. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8917
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
25.
Zhang, Weicheng.
DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION.
Degree: 2009, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/9308
► This thesis summarizes the author’s graduate research on catalytic asymmetric hydrogenation at Penn State. The first chapter gives a brief review of ligand development in…
(more)
▼ This thesis summarizes the author’s graduate research on catalytic asymmetric hydrogenation at
Penn State. The first chapter gives a brief review of ligand development in asymmetric hydrogenation, with a focus on the long-term effort of the Zhang group in this area. Several important factors for ligand design are discussed, including steric hindrance, electronic control, and practical considerations. Chapter 2 delineates the development of a novel triphosphorus bidentate phosphine-phosphoramidite ligand with pseudo C2-symmetry, from initial design, through ligand synthesis and characterization, to its application in asymmetric hydrogenation. A major success of this ligand is highlighted in asymmetric hydrogenation of ortho substituted á-arylenamides with excellent enantioselectivity (up to 99.6% ee), which had not been possible prior to this work. In Chapter 3, the development of conformationally rigid spirocyclic monodentate phosphoramidite ligands is discussed. A highly efficient, large-scale route for the synthesis of chiral spirocyclic diol is presented, followed by the discovery of an interesting acid-mediated rearrangement of spirocyclic backbones. These spirocyclic ligands are applied in highly enantioselective catalytic asymmetric hydrogenation and asymmetric conjugate addition reactions.
Advisors/Committee Members: Prof Xumu Zhang, Dissertation Advisor/Co-Advisor, Xumu Zhang, Committee Chair/Co-Chair, Scott Trent Feldman, Committee Chair/Co-Chair, Steven M Weinreb, Committee Member, Gong Chen, Committee Member, Qing Wang, Committee Member.
Subjects/Keywords: hydrogenation; asymmetric; catalysis; ligand; rhodium
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, W. (2009). DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/9308
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zhang, Weicheng. “DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION.” 2009. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/9308.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zhang, Weicheng. “DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION.” 2009. Web. 07 Mar 2021.
Vancouver:
Zhang W. DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION. [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/9308.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zhang W. DEVELOPMENT OF EFFECTIVE CHIRAL LIGANDS FOR CATALYTIC ASYMMETRIC HYDROGENATION. [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/9308
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
26.
Sun, Lu.
LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
.
Degree: 2009, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/9538
► The cerebellum is a brain structure essential for motor control and coordination, as well as motor learning and memory. The highly organized anatomy of the…
(more)
▼ The cerebellum is a brain structure essential for motor control and coordination, as well as motor learning and memory. The highly organized anatomy of the cerebellum makes it a good model for the study of network function. As the only output of the cerebellar cortex, Purkinje cells are considered as the cellular basis for certain types of motor learning. Purkinje cells receive excitatory synaptic inputs from parallel fibers and climbing fibers, and inhibitory inputs from GABAergic interneurons located at the molecular layer of the cerebellum. Since the activity of Purkinje cells is largely regulated by the synaptic integration, knowledge about cerebellar granule cells and interneurons is necessary for the understanding of the mechanism of motor learning and memory.
Interneurons including stellate cells and basket cells obtain afferent excitatory inputs from parallel fibers and project inhibitory inputs onto Purkinje cells, and thus form a feed-forward inhibition network. The inhibition from the interneurons counteracts the excitatory effects from parallel fibers and prevents the Purkinje cells from being over excited. However, the synaptic plasticity of the interneurons remains elusive. Using stellate cell as a model, we investigated the function of glutamate receptors in the synaptic plasticity in interneurons and the consequent impact on the pattern of GABA release from interneuron axonal terminals, which directly determines the inhibition of Purkinje cells. We observed that the activation of extrasynaptic NMDA receptors could induce a new form of synaptic plasticity at the parallel fiber-to-stellate cell synapse, including a subtype switch of AMPA receptors from naturally GluR2-lacking (Ca2+-permeable) to GluR2-containing (Ca2+-impermeable). This plasticity is probably postsynaptically induced and requires protein kinase C (PKC) and the activity of protein interacting with PRKCA 1 (PICK1). In addition, previous studies showed that the activation of NMDA receptors directly triggered a long-lasting potentiation of GABA release at axonal terminals. Our work about the characterization of NMDA receptors in stellate cells suggested the possible expression of NR2B and NR2D subunits. However, blockade of single subtype of NMDA receptors did not affect the basal level of GABA release.
Changes in synaptic transmission would alter the excitability of a cell and therefore affect the action potential firing pattern. We explored if action potential firing would in return regulate the synaptic efficacy. We found that blockade of spontaneous action potentials (sAPs) in stellate cells induced an increased expression of GluR2-containing AMPA receptors at the parallel fiber-to-stellate cell synapse. This effect might be transcription-independent, but requires intact protein synthesis machinery. Moreover, inhibition of calmodulin mimicked the effect of sAP blockade, indicating the sAP blockade-induced GluR2 expression may be mediated by a reduced calmodulin activity.
Our study revealed mechanisms underlying long-term plasticity…
Advisors/Committee Members: Si Qiong Liu, Dissertation Advisor/Co-Advisor, Si Qiong Liu, Committee Chair/Co-Chair, Matthew Whim, Committee Member, Bernhard Luscher, Committee Member, Steven Schiff, Committee Member, Gong Chen, Committee Member.
Subjects/Keywords: calmodulin; action potential; extrasynaptic; NMDA receptor; PICK; PKC; AMPA receptor; synaptic plasticity; GABAergic interneuron; cerebellum; protein synthesis; electrophysiology
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sun, L. (2009). LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/9538
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Sun, Lu. “LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
.” 2009. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/9538.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Sun, Lu. “LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
.” 2009. Web. 07 Mar 2021.
Vancouver:
Sun L. LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
. [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/9538.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Sun L. LONG-TERM SYNAPTIC PLASTICITY IN MOUSE CEREBELLAR STELLATE CELLS
. [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/9538
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
27.
Zamule, Stephanie M.
ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.
Degree: 2010, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/10496
► The liver performs an array of functions vital to life including detoxification, production of serum proteins, maintenance of cholesterol homeostasis, production and clearance of bile…
(more)
▼ The liver performs an array of functions vital to life including detoxification, production of serum proteins, maintenance of cholesterol homeostasis, production and clearance of bile components, assembly and inter-conversion of amino acids, synthesis and breakdown of glucose, and processing of fatty acids. Current treatments for liver failure are inadequate, relying on liver or hepatocyte transplantation, both of which are significantly limited by insufficient donor tissue, donor-to-donor variability in tissue quality, and the risk of rejection, infection, or adverse immune response in the recipient. Human embryonic stem cells (hESCs) – derived from the inner cell mass of developing blastocysts and capable of giving rise to any cell type in the body upon exposure to the appropriate conditions – offer promise as an alternative source of cells from which a supply of hepatocytes may be derived for therapeutic transplantations. Hepatocytes derived from hESCs would also potentially provide a repository of cells for pharmacological and toxicological studies which rely on hepatocytes obtained from human donors as models for drug metabolism research and predictors of toxicological responses that may be associated with exposure to xenobiotic compounds. While a number of studies have demonstrated that hESCs are capable of differentiating into hepatic precursors, the precise means by which these cells may be derived, and the genes governing this multifaceted process, have yet to be fully elucidated. In this investigation we employed a unique hepatic differentiation protocol in which hESCs are cultured for only 10 days on collagen matrix in our hepatocyte media (William’s E Media supplemented with HEPES, glutamine, antibiotics, dexamethasone, insulin, transferrin, selenium, and linoleic acid/albumin). The resulting cell population exhibits hepatic-like cell morphology and decreased expression of ‘stemness’ markers including certain transcription factors, surface antigens, and enzymes. The hESC-derived hepatic-like cells express enhanced levels of hepatic markers including transcription factors, nuclear receptors, liver-generated plasma proteins, protease inhibitors, metabolic enzymes, and biotransformation enzymes. Acquisition of hepatic function is confirmed by the cells’ ability to transport anionic compounds and store glycogen. Notably, expression of the constitutive androstane receptor (CAR) – a nuclear receptor which, in the adult liver, is involved in the regulation of diverse physiological processes including all three phases of hepatic biotransformation and elimination as well as energy metabolism and lipid homeostasis – is highly increased in the hepatic-like cells, to levels approaching those of cultures of primary human hepatocytes. CAR is also expressed robustly and consistently in human fetal liver tissue obtained from subjects of a range of gestational ages. Modulation of CAR levels in differentiating hESCs using a lentivirus system – which we demonstrate to stably and robustly transduce both hESCs and cultures…
Advisors/Committee Members: Curtis John Omiecinski, Dissertation Advisor/Co-Advisor, Curtis John Omiecinski, Committee Chair/Co-Chair, Gong Chen, Committee Member, Peter John Hudson, Committee Member, Gary H Perdew, Committee Member, John Patrick Vanden Heuvel, Committee Member, Kent Eugene Vrana, Committee Member.
Subjects/Keywords: embryonic stem cells; constitutive androstane receptor; liver; differentiation; nuclear receptor; development; lentivirus
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zamule, S. M. (2010). ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10496
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Zamule, Stephanie M. “ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.” 2010. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/10496.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Zamule, Stephanie M. “ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.” 2010. Web. 07 Mar 2021.
Vancouver:
Zamule SM. ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/10496.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Zamule SM. ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/10496
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
28.
Wu, Runzhi.
SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES.
Degree: 2010, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/11134
► RNA viruses cause a wide variety of diseases including SARS, influenza, hepatitis C and polio. Therapeutics for RNA virus infections are often limited because of…
(more)
▼ RNA viruses cause a wide variety of diseases including SARS, influenza, hepatitis C and polio. Therapeutics for RNA virus infections are often limited because of the rapid development of antiviral drug resistance. RNA viruses are known to exhibit high error rates during replication and thus exist as quasispecies. To maintain the maximum adaptability, these viruses exist on the edge of “error catastrophe”, and small increases in the mutation frequency can cause a drastic decrease in viral infectivity. By taking advantage of the high mutation rate of RNA virus replication, a relatively new antiviral approach termed “lethal mutagenesis” can be used to increase the error rate of RNA viral replication to intolerable levels, resulting in the loss of viral viability.
Chapter one of this dissertation reviews current antiviral therapeutics and lethal mutagenesis as an antiviral strategy. The clinically used antiviral drug ribavirin represents an agent that functions as a lethal mutagen against poliovirus (PV) and hepatitis C virus (HCV). This drug is converted intracellularly to the 5'-triphosphate (RTP), which is a degenerate substrate of viral RNA-dependent RNA polymerases (RdRP). Once in the genome, ribavirin promotes mutagenesis by templating the incorporation of both C and U during multiple rounds of viral replication, leading to error catastrophe and decreased infectivity of the virus.
The work described herein includes efforts to design and synthesize novel antiviral nucleosides and probe their mechanism of action. In chapter two, we report the synthesis and antiviral effects of bioisosteric deaza analogues of 6-methyl-9-β-D-ribofuranosylpurine, a hydrophobic analogue of adenosine. Whereas the 1-deaza and 3-deaza analogues are essentially inactive in whole cell assays, a novel 7-deaza-6-methyl-9-β-D-ribofuranosylpurine analogue, structurally related to the natural product tubercidin, potently inhibited replication of poliovirus (PV) in HeLa cells (IC50 = 11 nM) and dengue virus (DENV) in Vero cells (IC50 = 62 nM) as evidenced by plaque assays. Moreover, selectivity against PV over cytotoxic effects to HeLa cells was >100-fold after incubation for 7 h. We further found that the putative triphosphate metabolite of this 7-deaza analogue was effectively incorporated into RNA by PV RdRP.
Chapter three describes studies of the pyrazinecarboxamide compound T-1106 as an antiviral agent. Although this compound is active against several RNA viruses, its mechanism of action is poorly understood. Only a single patent has reported the synthesis of T-1106, and the coupling of its nucleobase with ribose leads to a mixture of α and β anomers. Improved Vorbrüggen coupling conditions were developed here to achieve a stereoselective synthesis of this compound. Treatment of PV infected HeLa cells with 1 mM T-1106 caused a dramatic decrease of viral titer, and the corresponding triphosphate was found to be incorporated by PV RdRP across all four natural nucleotides.
Chapter four focuses on another topic, development of…
Advisors/Committee Members: Dr Blake R Peterson, Dissertation Advisor/Co-Advisor, Raymond Lee Funk, Committee Chair/Co-Chair, Blake R Peterson, Committee Member, Philip C. Bevilacqua, Committee Member, Gong Chen, Committee Member, Avery August, Committee Member.
Subjects/Keywords: antiviral agent; nucleoside; fluorescent molecule
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Wu, R. (2010). SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11134
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Wu, Runzhi. “SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES.” 2010. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/11134.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Wu, Runzhi. “SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES.” 2010. Web. 07 Mar 2021.
Vancouver:
Wu R. SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/11134.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Wu R. SYNTHESIS OF NOVEL ANTIVIRAL AGENTS AND FLUORESCENT MOLECULAR PROBES. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11134
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University
29.
Silva, Ricardo Jose.
STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE.
Degree: 2008, Penn State University
URL: https://submit-etda.libraries.psu.edu/catalog/6759
► A novel in vitro electrophysiological technique was developed, based on the use of a large summing population electrode (macroelectrode approach). The macroelectrode approach was utilized…
(more)
▼ A novel in vitro electrophysiological technique was developed, based on the use of a large summing population electrode (macroelectrode approach). The macroelectrode approach was utilized to study the evolution of the electrical response in the SK-N-BE(2c) human neuroblastoma cell line. Development of a large oscillatory electrical signal consistent with the establishment of a functional pacing network in culture was observed. Neural pacing is a phenomenon of fundamental importance in neurosciences. Pacing is an integrating factor in the developing brain, learning, memory and motor coordination. The nature and origin of this signal was studied by means of the macroelectrode approach as well as patch clamping, liquid chromatography, and immunofluorescence. By comparing the signal obtained with the macroelectrode approach to traditional methods the strength and weaknesses of the technique were explored. It was determined that pacing networks naturally develop in this cell line and are the result of synaptic communication mediated by dopamine as a neurotransmitter and dopamine D2 as a receptor. The macroelectrode technique was shown to provide unique information about the population behavior of cells growing in culture. The electrical properties of the SK-N-BE(2c) cell line as seen with the macroelectrode approach could serve as a cost effective solution for long term, real time study of pacing neural networks in vitro and the basis for the development of cell based biosensors and high throughput drug screening systems.
Advisors/Committee Members: Roger Paul Gaumond, Committee Chair/Co-Chair, Gong Chen, Committee Member, Byron C Jones, Committee Member, Harry R Allcock, Committee Member, Nandini Vasudevan, Committee Member, Jeffrey D Zahn, Committee Member.
Subjects/Keywords: macroelectrode; neuroblastoma; autocorrelation; neuroscience; bioengineering; neural engineering; biotechnology; electrophysiology; biomaterials
Record Details
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Record Details
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Silva, R. J. (2008). STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Silva, Ricardo Jose. “STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE.” 2008. Thesis, Penn State University. Accessed March 07, 2021.
https://submit-etda.libraries.psu.edu/catalog/6759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Silva, Ricardo Jose. “STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE.” 2008. Web. 07 Mar 2021.
Vancouver:
Silva RJ. STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07].
Available from: https://submit-etda.libraries.psu.edu/catalog/6759.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Silva RJ. STUDY OF A PACING NEUROBLASTOMA CELL LINE VIA A NOVEL MACROELECTRODE TECHNIQUE. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6759
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
.