+publisher:"Penn State University" +contributor:("Sergei A Grigoryev, Committee Member")

Penn State University

1. Tuffy, Kevin Michael. NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION.

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/13172kxt247

► The ability for the retroviral Gag protein of Rous sarcoma virus (RSV) to transiently traffic through the nucleus is well established and has been implicated… (more)

Subjects/Keywords: HIV-1; Gag; viral RNA

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

APA (6^th Edition):

Tuffy, K. M. (2016). NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/13172kxt247

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

Chicago Manual of Style (16^th Edition):

Tuffy, Kevin Michael. “NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION.” 2016. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/13172kxt247.

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

MLA Handbook (7^th Edition):

Tuffy, Kevin Michael. “NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION.” 2016. Web. 13 Apr 2021.

Vancouver:

Tuffy KM. NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/13172kxt247.

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

Council of Science Editors:

Tuffy KM. NUCLEAR HIV-1 GAG SPECIFICALLY ASSOCIATES WITH UNSPLICED VIRAL RNA DURING TRANSCRIPTION. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/13172kxt247

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

Penn State University

2. Horvath, Lindsay Marie. Deletion of an X-inactivation boundary disrupts adjacent gene silencing.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/19799

► In mammalian females, genes on one X chromosome are largely silenced by X-chromosome inactivation (XCI), although some “escape” XCI and are expressed from both X… (more)

Subjects/Keywords: X chromosome; gene expression; domain boundary; boundary regulation; X-chromosome inactivation

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APA (6^th Edition):

Horvath, L. M. (2013). Deletion of an X-inactivation boundary disrupts adjacent gene silencing. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/19799

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

Chicago Manual of Style (16^th Edition):

Horvath, Lindsay Marie. “Deletion of an X-inactivation boundary disrupts adjacent gene silencing.” 2013. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/19799.

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

MLA Handbook (7^th Edition):

Horvath, Lindsay Marie. “Deletion of an X-inactivation boundary disrupts adjacent gene silencing.” 2013. Web. 13 Apr 2021.

Vancouver:

Horvath LM. Deletion of an X-inactivation boundary disrupts adjacent gene silencing. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/19799.

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

Council of Science Editors:

Horvath LM. Deletion of an X-inactivation boundary disrupts adjacent gene silencing. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/19799

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

Penn State University

3. Russo, Mariano. IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES.

Degree: 2019, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16792mur122

► This dissertation uses genomic analyses of FFPE (Formalin-Fixed Paraffin-Embedded) cancer tissues to investigate biomarkers of clinical pathologies of thyroid, endometrial, and bladder cancer. Thyroid cancer… (more)

▼ This dissertation uses genomic analyses of FFPE (Formalin-Fixed Paraffin-Embedded) cancer tissues to investigate biomarkers of clinical pathologies of thyroid, endometrial, and bladder cancer. Thyroid cancer demonstrates a unique switch in the overall incidence of driver mutations in a population upon exposure to radiation. This radiation switch has previously been described for thyroid cancer cases exposed to fallout from the Chernobyl nuclear meltdown and atomic bomb survivors. We demonstrated in a small cohort of individuals who were exposed to the TMI meltdown a similar radiation induced shift in driver mutation profile compared to individuals who developed thyroid cancer before the accident or long after, suggesting a previously uncharacterized health effect of the TMI meltdown on the nearby population. Endometrial hyperplasia is considered a neoplastic precursor to endometrial adenocarcinoma. The subtypes of endometrial hyperplasia, atypical or non-atypical, demonstrate large differences in the probability of progression to adenocarcinoma; however, their histopathological distinction is challenging. We conducted two studies to determine the genomic differences between adenocarcinoma, atypical endometrial hyperplasia, and non-atypical endometrial hyperplasia. The first study compared concurrent endometrial adenocarcinoma and atypical hyperplasia in six cases. We identified several common driver mutations, such as PTEN and PIK3CA, in both adenocarcinoma and atypical hyperplasias. We also identified further driver mutations in both the adenocarcinoma and the atypical hyperplasia exclusive to the corresponding lesion. This pattern suggests non-linear evolutionary pathways arising from a common precursor. In our subsequent study, we compared the genomic profiles of non-atypical hyperplasia and atypical hyperplasia. We divided these cases into progressing and resolving hyperplasia in order to define the genomic characteristics that predict progression to adenocarcinoma. We identified PI3K pathway mutations in both progressing and resolving hyperplasia; however, progressing hyperplasia demonstrated accumulation of mutations in this pathway as well as receptor tyrosine kinase mutations along with ARID1A. This profile of mutations may aid clinical diagnostics. Non-muscle invasive bladder cancer (NMIBC) is easily treated by transurethral resection (TUR), however, these lesions commonly recur (up to 78% of cases) and recurrences may progress to muscle invasion. Our study identified a small cohort of low stage NMIBC divided into recurring and non-recurring. Although our cohort was underpowered, we identified trends in biomarkers of recurrence of NMIBC. These trends involve mutated STAG2 and the accumulation of mutations in DNA repair and cell cycle regulation pathways. These studies propose several gene and pathway biomarkers that can aid clinical diagnostics and warrant additional investigation in larger cohorts. Advisors/Committee Members: James Riley Broach, Dissertation Advisor/Co-Advisor, James Riley Broach, Committee Chair/Co-Chair, Feng Yue, Committee Member, Nancy Louise Lill, Committee Member, Charles H Lang, Outside Member, Sergei A Grigoryev, Committee Member.

Subjects/Keywords: Next Generation Sequencing; FFPE; Ion Torrent; Endometrial Hyperplasia; Bladder Cancer; Thyroid Cancer

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

APA (6^th Edition):

Russo, M. (2019). IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16792mur122

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

Chicago Manual of Style (16^th Edition):

Russo, Mariano. “IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES.” 2019. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/16792mur122.

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

MLA Handbook (7^th Edition):

Russo, Mariano. “IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES.” 2019. Web. 13 Apr 2021.

Vancouver:

Russo M. IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES. [Internet] [Thesis]. Penn State University; 2019. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/16792mur122.

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

Council of Science Editors:

Russo M. IDENTIFYING UNIQUE BIOMARKERS IN GENOMICS STUDIES OF THYROID, ENDOMETRIAL, AND BLADDER CANCER FROM FFPE TISSUES. [Thesis]. Penn State University; 2019. Available from: https://submit-etda.libraries.psu.edu/catalog/16792mur122

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

Penn State University

4. Barnes, Ryan Patrick. The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites.

Degree: 2017, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/14528rpb180

► Replicative DNA polymerases serve as the essential enzymes that duplicate our genome with high fidelity and efficiency. This function is compromised however, when repetitive DNA… (more)

▼ Replicative DNA polymerases serve as the essential enzymes that duplicate our genome with high fidelity and efficiency. This function is compromised however, when repetitive DNA sequences adopt a structure differing from the Watson-Crick B-form or during conditions of replicative stress. However, cells also possess specialized DNA polymerases that can compensate for the replicative polymerases when they are inhibited. The goals of this thesis were to investigate how the specialized DNA polymerases (Pols) eta (η) and kappa (κ) 1) cooperate with the replicative polymerase delta (δ) in the synthesis of repetitive DNA derived from chromosomal fragile sites, and 2) understand how these enzymes function during cellular replication stress. Common fragile sites (CFSs) are genomic loci that display recurrent instability in cells experiencing replication stress. Replication stress, defined as the slowing or stalling of replication forks, occurs when cells are treated with agents that inhibit DNA synthesis or are deficient in DNA repair/replication enzymes. CFSs are sensitive to replication stress, and one rationale for this is their enrichment in repetitive DNA sequences that can adopt a non-B DNA structure. Previous work in the Eckert lab has shown that all three replicative, human DNA polymerases are inhibited by repetitive CFS sequences in vitro whereas polymerases η and κ can replicate the same sequences with high efficiency. In chapter 3, I test the hypothesis that Pols η and κ can cooperate with Pol δ in CFS sequence replication in vitro. To investigate this, I developed a model of lagging strand synthesis using primed ssDNA templates containing RFC-loaded PCNA, the processivity factor of Pol δ. This system was designed to allow RFC and Pols δ, η, and κ to function optimally in the same reaction conditions. Using this system, I found that Pols η and κ can indeed rescue the Pol δ holoenzyme (Pol δ/ RFC-loaded PCNA; Pol δHE) stalled at CFS sequences containing different repetitive DNA motifs. I found this polymerase cooperativity was not mediated by PCNA however, as reactions where RFC was omitted displayed no defect in replication rescue. Moreover, using this system I did not observe any enhancement of cooperativity between Pol δ and Pols η and κ using mono-ubiquitinated PCNA (Ub-PCNA), a post-translational modification thought to regulate polymerase exchange at DNA lesions. Finally, by modeling replication stress in vitro using Aph, a drug that directly inhibits replicative polymerases, I found that Pols η and κ become indispensable for repetitive CFS sequence replication. In total, the data in this chapter advances our understanding of human DNA polymerase exchange, and how repetitive DNA replication is accomplished by multiple polymerases. While the relationship between CFS stability and Pol η has been characterized by work in the Eckert lab and others, we did not know how Pol η might impact the cell cycle and checkpoint signaling in replication stressed cells. To study this, I employed several models of… Advisors/Committee Members: Kristin Ann Eckert, Dissertation Advisor/Co-Advisor, Kristin Ann Eckert, Committee Chair/Co-Chair, George Lucian Moldovan, Committee Member, James Riley Broach, Committee Member, Edward Joseph Gunther, Outside Member, Sergei A Grigoryev, Committee Member.

Subjects/Keywords: DNA polymerase; replication stress; genome stability

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

APA (6^th Edition):

Barnes, R. P. (2017). The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/14528rpb180

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

Chicago Manual of Style (16^th Edition):

Barnes, Ryan Patrick. “The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites.” 2017. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/14528rpb180.

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

MLA Handbook (7^th Edition):

Barnes, Ryan Patrick. “The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites.” 2017. Web. 13 Apr 2021.

Vancouver:

Barnes RP. The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites. [Internet] [Thesis]. Penn State University; 2017. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/14528rpb180.

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

Council of Science Editors:

Barnes RP. The Roles and Regulation of Specialized DNA Polymerases in Mitigating Replication Stress and Replicating Common Fragile Sites. [Thesis]. Penn State University; 2017. Available from: https://submit-etda.libraries.psu.edu/catalog/14528rpb180

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

Penn State University

5. Lochmann, Timothy Lewis. A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12452

► The assembly of retrovirus particles is directed by the retroviral Gag polyprotein. The Rous sarcoma virus (RSV) Gag polyprotein is synthesized in the cytoplasm. During… (more)

▼ The assembly of retrovirus particles is directed by the retroviral Gag polyprotein. The Rous sarcoma virus (RSV) Gag polyprotein is synthesized in the cytoplasm. During the early steps of assembly, Gag undergoes transient nuclear trafficking mediated by nuclear localization signals (NLSs) in the matrix (MA) and nucleocapsid (NC) domains, and a nuclear export signal (NES) present within the p10 domain. Gag nuclear trafficking has been linked to efficient packaging of viral genomic RNA. However, whether Gag undergoes intranuclear trafficking and what host factors Gag may interact with in the nucleus remains poorly understood. The ability to mutate the NES and inhibit nuclear export makes RSV a useful model to study the roles of Gag within the nucleus and how Gag interacts with nuclear factors during retrovirus infection. Experiments aimed at identifying Gag-Gag interactions within the nucleus revealed that Gag proteins accumulated within punctate nuclear foci. These subnuclear foci were not virus-like particles forming within the nucleus. The formation of Gag-containing foci was dependent upon the presence of NC, which is an RNA binding domain. Further studies revealed that Gag nuclear puncta were anchored within the nucleoplasm at discrete locations, but individual Gag molecules move between the subnuclear structures and the nucleoplasm. These results suggest that the Gag proteins are retained at a particular subnuclear structure, perhaps being anchored there by an interaction with a cellular protein or RNA molecule. In addition to nucleoplasmic foci, Gag also accumulated within nucleoli in an NC-dependent manner. Similar to the nuclear puncta, Gag proteins moved in and out of nucleoli. Using site-directed mutagenesis, the amino acids involved in nucleolar localization of NC were identified. Furthermore, mutations that eliminated nucleolar localization of NC also prevented Gag from accumulating within nucleoli. These results indicate that NC plays a key role in the nucleolar localization and subnuclear trafficking of the Gag protein. However, whether these nuclear accumulations of Gag serve a purpose during viral replication is unknown. To determine whether nucleolar localization was involved in retroviral replication, proviral vectors were used to examine how mutations to the basic residues within NC affected virus particle release, gRNA packaging, and infectivity. In general, mutations that reduced NC nucleolar localization did not affect particle release, but gRNA packaging and infectivity were impaired in some viral mutants. The presence of a minimal number of positively charged residues within NC is not linked to gRNA packaging, although the location of the basic residues was important. Elimination of NC nucleolar localization reduced the ability of the virus to spread in infectivity assays. Together, these results suggest that NC nucleolar localization is important for infectivity, but not gRNA packaging or virus particle release. To further examine the role of nucleoli in retroviral infection,… Advisors/Committee Members: Leslie Joan Parent, Dissertation Advisor/Co-Advisor, Leslie Joan Parent, Committee Chair/Co-Chair, David Joseph Spector, Committee Member, Jianming Hu, Committee Member, Sergei A Grigoryev, Committee Member, Christopher Herzog, Committee Member.

Subjects/Keywords: packaging; retrovirus; assembly; trafficking; nucleoli; RSV

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

APA (6^th Edition):

Lochmann, T. L. (2011). A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12452

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

Chicago Manual of Style (16^th Edition):

Lochmann, Timothy Lewis. “A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein .” 2011. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/12452.

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

MLA Handbook (7^th Edition):

Lochmann, Timothy Lewis. “A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein .” 2011. Web. 13 Apr 2021.

Vancouver:

Lochmann TL. A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/12452.

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

Council of Science Editors:

Lochmann TL. A Journey to the Center of the Cell: Insights Into Subnuclear Trafficking of the Rous Sarcoma Virus Gag Polyprotein . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12452

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

Penn State University

6. Bao, Jialing. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12670

► Meprin metalloproteases have been implicated in a number of normal developmental and pathological processes. However, it has been difficult to establish the cellular and molecular… (more)

▼ Meprin metalloproteases have been implicated in a number of normal developmental and pathological processes. However, it has been difficult to establish the cellular and molecular basis for the biological role of meprin metalloproteases in health and disease, possibly because of the large number of metalloproteases, many having overlapping substrate specificities. A number of important biological molecules have been demonstrated to be meprin substrates in vitro, such as extracellular matrix and cytokines. With the development of congenic mice lacking meprin activity, it has been possible to relate in vitro results with in vivo data to examine cellular and molecular processes. The hypothesis of the thesis work is that meprins relax epithelial barriers by cleaving tight junction proteins, and facilitate monocyte migration. The study demonstrated that homomeric meprin A and meprin B cleaved the tight junction protein occludin, but not claudin-4, in membrane fractions from MDCK cells. Meprin A, but not meprin B, added exogenously to MDCK monolayers cleaved occludin. Meprin A, but not meprin B, cleaved recombinant occludin extracellular loops, and the cleavage site was determined in the first extracellular loop of occludin. Different cleavage site preferences at extracellular regions explain the different results between meprin A and meprin B to cleave occludin in intact cells and cell extacts. The biological relevance of the in vitro experiments was demonstrated by studies in cell culture, in vivo and ex vivo. Meprin A disrupted the immunostaining of tight junction proteins occludin and ZO-1 on MDCK monolayers. In addition, meprin A impaired the barrier function of MDCK monolayers, as shown by increased small molecule flux and decreased transepithelial electrical resistance. To elucidate the role of meprin A in acute urinary tract infections, meprin A was infused into the mouse bladder and the effects on bladder epithelium wall was investigated. The results showed that active meprin A increased the permeability of the epithelium as demonstrated by the influx of a fluorescene dye. The hypothesis that meprin A disrupts epithelial barriers and facilitates monocyte migration was further investigated by co-culturing monocytes with MDCK monolayers and measuring monocyte migration. Monocytes from mice lacking meprin A (meprin KO) were less able to migrate through MDCK monolayers than monocytes from wild-type mice. It is concluded that the capability of meprin A to disrupt epithelial barriers is one important factor by which meprin A modulates inflammation. Advisors/Committee Members: Judith S Bond, Dissertation Advisor/Co-Advisor, Gail Lynn Matters, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, W. Brian Reeves, Committee Member, Harriet C Isom, Committee Member.

Subjects/Keywords: Meprin; Tight junctions; Occludin; Epithelial barrier; Monocyte

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

APA (6^th Edition):

Bao, J. (2012). Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12670

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

Chicago Manual of Style (16^th Edition):

Bao, Jialing. “Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.” 2012. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/12670.

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

MLA Handbook (7^th Edition):

Bao, Jialing. “Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration.” 2012. Web. 13 Apr 2021.

Vancouver:

Bao J. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/12670.

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

Council of Science Editors:

Bao J. Meprin Metalloproteases Modulate Epithelial Barrier Integrity and Monocyte Migration. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/12670

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

Penn State University

7. Rennoll, Sherri Ann. Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26902

► Over 90% of sporadic colorectal cancers (CRCs) are associated with initiating mutations in components of the Wnt/β-catenin signaling pathway. These mutations result in elevated nuclear… (more)

▼ Over 90% of sporadic colorectal cancers (CRCs) are associated with initiating mutations in components of the Wnt/β-catenin signaling pathway. These mutations result in elevated nuclear levels of the β-catenin transcriptional co-activator. In the nucleus, β-catenin associates with the T-cell factor/Lymphoid enhancer factor (TCF/Lef) family of sequence-specific transcription factors at Wnt-responsive DNA elements (WREs) to increase target gene expression. Aberrant expression of these genes by oncogenic Wnt/β-catenin signaling leads to the formation of small, benign adenomas. The c-MYC (MYC) proto-oncogene is a direct β-catenin target gene that is required for Wnt/β-catenin-mediated intestinal tumorigenesis. However, the molecular mechanisms underlying β-catenin regulation of MYC expression are not fully defined. The work described within this thesis aimed to further define these molecular mechanisms by addressing the involvement of nuclear AXIN2 and the MYC 3’ WRE in controlling oncogenic MYC gene expression. AXIN2, a scaffolding protein and component of the Wnt/β-catenin signaling pathway, was recently demonstrated to localize to the nucleus. The function of AXIN2 within this subcellular compartment, however, was unknown. By constitutively localizing AXIN2 to the nucleus, we demonstrate that nuclear AXIN2 forms a complex with β-catenin/TCF and represses MYC gene expression by binding the MYC gene locus. These results indicate that nuclear AXIN2 functions as a molecular rheostat to maintain a “just right” level of MYC necessary for tumorigenesis in CRC. Similar to nuclear AXIN2, we find that the MYC 3’ WRE, which maps 1.4-kb downstream from the MYC transcription stop site, drives oncogenic MYC gene expression in CRC cells. Using CRISPR/Cas9 genome editing technology, we generated a knockout CRC cell line in which a single TCF binding element within the MYC 3’ WRE was deleted. Deletion of this element decreased β-catenin/TCF occupancy at the MYC 3’ WRE and MYC gene expression. The observed decrease in MYC gene expression corresponded to diminished cellular proliferation and growth of the knockout cells. Together, our studies have uncovered new mechanisms for regulation of MYC gene expression by oncogenic Wnt/β-catenin signaling, and suggest that approaches to target nuclear AXIN2 or the MYC 3’ WRE would be effective strategies for the treatment of individuals suffering from CRC. Advisors/Committee Members: Gregory Yochum, Dissertation Advisor/Co-Advisor, Gregory Yochum, Committee Chair/Co-Chair, Laura Carrel, Committee Member, Sergei A Grigoryev, Committee Member, Lisa M Shantz, Committee Member.

Subjects/Keywords: MYC; beta-catenin; AXIN2; colorectal cancer

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

APA (6^th Edition):

Rennoll, S. A. (2015). Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26902

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

Chicago Manual of Style (16^th Edition):

Rennoll, Sherri Ann. “Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas.” 2015. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/26902.

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

MLA Handbook (7^th Edition):

Rennoll, Sherri Ann. “Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas.” 2015. Web. 13 Apr 2021.

Vancouver:

Rennoll SA. Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/26902.

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

Council of Science Editors:

Rennoll SA. Transcriptional regulation of the c-MYC (MYC) proto-oncogene by oncogenic Wnt/β-catenin signaling in colorectal carcinomas. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26902

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

Penn State University

8. Steffens, Sadie Lynne. Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/27412

► Acute myeloid leukemia (AML) is a malignant disease of the myeloid line of blood cells and is characterized by the rapid growth of abnormal white… (more)

▼ Acute myeloid leukemia (AML) is a malignant disease of the myeloid line of blood cells and is characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. Cytarabine and other currently available treatments for acute myeloid leukemia are highly toxic and insufficient, as more than half of all AML patients develop resistance to chemotherapeutic agents. Since AML often affects older people who are less tolerant of chemotherapy, there is need for novel, targeted, less toxic drugs in order to improve survival for this disease. Casein Kinase II (CK2) is a pro-oncogenic serine/threonine kinase that is essential for cellular proliferation. Overexpression or increased CK2 activity is associated with various types of human malignancies. In hematopoietic cells, increased CK2 expression is associated with malignant transformation and development of leukemia. Increased CK2 activity is associated with a poor prognosis in AML. Targeted inhibition of CK2 with a novel, specific inhibitor produced a strong anti-leukemia effect in vitro and in pre-clinical models. However, the mechanism through which CK2 inhibitors exert an anti-leukemia effect is unknown. The goal of our project is to identify the mechanism of the therapeutic activity of CK2 inhibition using CX-4945 in AML. Ikaros is a zinc finger, DNA-binding protein that is encoded by the IKZF1 gene and acts as a tumor suppressor in hematopoietic malignancies. Deletion or functional inactivation of Ikaros is associated with development of high-risk acute lymphoblastic leukemia (ALL) as well as AML. Previously published data showed that CK2 directly phosphorylates Ikaros at multiple evolutionarily-conserved sites. The CK2-mediated phosphorylation of Ikaros results in reduced DNA-binding affinity and loss of Ikaros function as a transcriptional regulator of gene expression. Inhibition of CK2 restores Ikaros function as a tumor suppressor and produces an anti-leukemia effect in ALL. Based on these data, we hypothesized that one of the mechanisms of therapeutic action of CK2 inhibitors in AML involves restoration of Ikaros function as a transcriptional regulator of genes involved in malignant transformation. Genome-wide binding studies using chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-Seq) demonstrated that inhibition of CK2 via CX-4945 in U937 and primary AML cells enhances Ikaros binding affinity at the promoter regions of its target genes. We used gain-of-function and loss-of-function experiments to determine how Ikaros regulates several novel target genes involved in malignant transformation and drug resistance. Results demonstrated that Ikaros directly represses transcription of the BCL2A1 gene, which promotes leukemogenesis and has an anti-apoptotic function. We show that the ability of Ikaros to repress transcription of BCL2A1 is impaired in AML, overexpression of BCL2A1 is a negative prognostic marker, and anti-apoptotic mechanisms contribute to… Advisors/Committee Members: Sinisa Dovat, Dissertation Advisor/Co-Advisor, Sinisa Dovat, Committee Chair/Co-Chair, Barbara Miller, Committee Member, Sergei A Grigoryev, Committee Member, Jong Kak Yun, Committee Member.

Subjects/Keywords: Ikaros; CK2; AML; drug resistance; BCL2A1; MTHFR; CDA; DLX1; DLX2; cytarabine; methotrexate; doxorubicin

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

APA (6^th Edition):

Steffens, S. L. (2015). Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/27412

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

Chicago Manual of Style (16^th Edition):

Steffens, Sadie Lynne. “Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia.” 2015. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/27412.

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

MLA Handbook (7^th Edition):

Steffens, Sadie Lynne. “Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia.” 2015. Web. 13 Apr 2021.

Vancouver:

Steffens SL. Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/27412.

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

Council of Science Editors:

Steffens SL. Mechanism of Drug Action of the Specific Ck2 Inhibitor Cx-4945 in Acute Myeloid Leukemia. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/27412

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

Penn State University

9. Kenney, Scott Patrick. INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/9234

► Assembly of retroviruses is mediated by a polyprotein termed Gag, which is both necessary and sufficient to drive particle assembly. Gag functional domains are conserved… (more)

▼ Assembly of retroviruses is mediated by a polyprotein termed Gag, which is both necessary and sufficient to drive particle assembly. Gag functional domains are conserved among retroviruses, and each Gag protein encodes a matrix, capsid, and nucleocapsid protein that serves specific functions during particle assembly. Numerous protein-interaction partners and conformational changes occur during the course of assembly to mediate each step of the process. In this dissertation, I present my work on the subcellular trafficking patterns of the Gag protein of the simple avian retrovirus Rous sarcoma virus (RSV) to gain insights into the role of nuclear transport mechanisms in the assembly of retroviruses. RSV Gag undergoes transient nuclear localization in which nuclear export is mediated through the host cellular factor CRM1. The nuclear trafficking step divides the assembly process into early (pre nuclear) and late (post nuclear) events. Utilizing a complementation approach, I found that Gag proteins interact early in the assembly process, either prior to nuclear import or within the nucleus. Under normal conditions, higher-ordered protein complex formation is prevented from occurring in the nucleus because of efficient nuclear export. However, in the overexpression system, Gag multimers form in the nucleus when Gag is capable of interacting with RNA. Through the use of CRM1-dependent and CRM1-independent nuclear export signal substitutions, I showed that CRM1-dependent export signals could substitute for the Gag nuclear export signal and virus assembly, although infectivity was impaired. In the course of these experiments, I made several novel observations. In addition to the CRM1-mediated nuclear export pathway, RSV Gag appears to be exported from the nucleus in a CRM1-independent manner. Furthermore, substitution of the p10 NES with heterologous NESs increased genomic RNA packaging, implicating the nuclear export sequence in Gag as a determinant for RNA incorporation. Finally, I showed that nuclear export activity of the Gag polyprotein can be genetically separated from the role of this region in virus replication. Together, these findings confirm that the region of Gag which regulates nuclear trafficking plays multiple overlapping roles in the viral lifecycle. Advisors/Committee Members: Leslie Joan Parent, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, John Warren Wills, Committee Member, Richard James Courtney, Committee Member, David Joseph Spector, Committee Member.

Subjects/Keywords: Retrovirus; retroviral assembly; Gag; p10; nuclear export; protein dimerization; FRET; FLIP; CRM1

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

APA (6^th Edition):

Kenney, S. P. (2008). INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/9234

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

Chicago Manual of Style (16^th Edition):

Kenney, Scott Patrick. “INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE.” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/9234.

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

MLA Handbook (7^th Edition):

Kenney, Scott Patrick. “INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE.” 2008. Web. 13 Apr 2021.

Vancouver:

Kenney SP. INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/9234.

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

Council of Science Editors:

Kenney SP. INSIGHTS INTO RETROVIRAL ASSEMBLY FROM MUTATION OF THE ROUS SARCOMA VIRUS p10 NUCLEAR EXPORT SEQUENCE. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/9234

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

Penn State University

10. Diep, Cuong Quoc. Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7356

► Transcriptional regulation of protein-encoding genes in eukaryotic organisms is required for proper development, differentiation, and response to environmental changes. The expression of specific genes at… (more)

▼ Transcriptional regulation of protein-encoding genes in eukaryotic organisms is required for proper development, differentiation, and response to environmental changes. The expression of specific genes at the transcriptional level is often tightly regulated to ensure that these genes are turned on or off only at the proper time and in the appropriate cell type. One of the most well studied cases of such regulation in eukaryotes is the GAL gene switch found in the yeast Saccharomyces cerevisiae. The GAL genes are necessary for the metabolism of galactose and their transcription is activated by a DNA-binding transcriptional activator, Gal4, in the presence of galactose. However, without galactose the activity of Gal4 is inhibited by its interaction with Gal80. A key regulatory component in activation of the GAL gene switch is the Gal3 protein. Gal3 senses the presence of intracellular galactose and binds to Gal80, relieving the Gal80-inhibition of Gal4. Although Gal3 interaction with Gal80 leads to Gal4-mediated activation of the GAL genes, there is a major gap of knowledge in how Gal3 itself is activated by galactose and ATP, and it is not known which amino acids of Gal3 are important for interaction with Gal80. In this thesis work, I addressed the mechanism in which Gal3 is activated by its ligands and also identified the surface and amino acids that are necessary for interaction with Gal80. Intragenic suppression analyses were performed for GAL3C mutants that confer a constitutive GAL gene activation and a galactose-independent interaction with Gal80. Of the five GAL3C alleles analyzed, four were suppressed by the second-site suppressor (GAL3SOC-D68S), while one allele (GAL3C-D368V) was not suppressed. On the Gal3 homology model, the suppressed GAL3C alleles co-localized with the second-site suppressor to the “hinge” region consisting of β-sheets s-C, -H and α-helices h-K, -O, whereas the non-suppressed allele localized to the opposite side of the “hinge” region at α-helix h-J. The GAL3C-D368V allele had previously been shown to suppress a GAL80S-G323R interaction mutation. Crosslinking results of Gal3 and Gal80 are consistent with the notion that they interact by surfaces that include Gal3-D368 and Gal80-G323. This is further supported by the localization of gal3 interaction mutants surrounding Gal3-D368 on the homology model. The data suggest that a local conformational change occurs within the “hinge” region to activate Gal3, while the interaction interface encompassing D368 plays a direct role in the binding to Gal80. Furthermore, based on considerations of E. coli galactokinase and previous attempts to isolate Gal3 interaction peptides, I conclude that the Gal80-binding surface of Gal3 is a composite of noncontiguous elements. Advisors/Committee Members: James E Hopper, Committee Chair/Co-Chair, Anita Klein Hopper, Committee Member, Sergei A Grigoryev, Committee Member, George Makhatadze, Committee Member, Vincent Chau, Committee Member.

Subjects/Keywords: GAL gene switch; transcription regulation; GAL3

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

APA (6^th Edition):

Diep, C. Q. (2008). Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7356

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

Chicago Manual of Style (16^th Edition):

Diep, Cuong Quoc. “Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch .” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/7356.

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

MLA Handbook (7^th Edition):

Diep, Cuong Quoc. “Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch .” 2008. Web. 13 Apr 2021.

Vancouver:

Diep CQ. Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/7356.

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

Council of Science Editors:

Diep CQ. Analysis of the yeast Gal3 protein, a key component of the GAL gene transcription switch . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7356

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

Penn State University

11. Prothero, Katie Eva. Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11407

► In female mammals, X chromosome inactivation (XCI) transcriptionally silences most genes on one X. Nonetheless, in humans, 15% of genes escape XCI and are expressed… (more)

▼ In female mammals, X chromosome inactivation (XCI) transcriptionally silences most genes on one X. Nonetheless, in humans, 15% of genes escape XCI and are expressed from both active and inactive Xs. Many of these escape genes are clustered, suggesting their expression is coordinately regulated. An attractive model is that these clustered escape genes are flanked by regulatory sequences such as insulators. To identify sequences that control XCI, I focused on a cluster of human escape genes that includes the Ubiquitin Activating Enzyme E1 gene, UBA1. UBA1 has a distinctive gene structure with five alternative promoters and 5’ untranslated exons that each splice to a single exon 2. Inactive X expression is also unique; two upstream exons are X-inactivated whereas two downstream exons assayed escape XCI. The 2.1 kb between X-inactivated and expressed exons is the smallest inactive X expression boundary and is a tractable region to identify sequences that regulate inactive X expression. To test the prediction that escape domains are regulated by chromatin insulators, eight overlapping constructs within the UBA1 boundary were tested; a 330 bp sequence demonstrated insulator function. Despite similar gene structure and high sequence conservation, all mouse Uba1 transcripts are X-inactivated and the locus lacks insulator activity. The UBA1 insulator is novel; while the insulator-binding protein CTCF has been identified at one XCI expression boundary, CTCF binds the UBA1 locus downstream of the insulator and appears unrelated to inactive X regulation. That the insulator is functional in XCI gene regulation is suggested by epigenetic modifications that specifically demarcate this sequence on the inactive X. Chromatin immunoprecipitation demonstrated that the UBA1 insulator segregates heterochromatin from the euchromatic escape domain. Additionally, DNA methylation differences distinguish the human insulator; this sequence is hypomethylated on the inactive X, whereas the active X is heavily methylated, as is the orthologous sequence that lacks boundary activity on both Xs in mouse. The identification of a novel insulator at the UBA1 expression boundary strengthens the model that escape domains are regulated by chromatin boundaries and pinpoints a region that can be further dissected to identify novel factors that bind and regulate XCI escape. Advisors/Committee Members: Laura Carrel, Dissertation Advisor/Co-Advisor, Laura Carrel, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, Ira Joseph Ropson, Committee Member, Jiyue Xhu, Committee Member.

Subjects/Keywords: DNA methylation; X chromosome inactivation; epigenetics

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

APA (6^th Edition):

Prothero, K. E. (2010). Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11407

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

Chicago Manual of Style (16^th Edition):

Prothero, Katie Eva. “Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene .” 2010. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/11407.

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

MLA Handbook (7^th Edition):

Prothero, Katie Eva. “Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene .” 2010. Web. 13 Apr 2021.

Vancouver:

Prothero KE. Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/11407.

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

Council of Science Editors:

Prothero KE. Identification of a CTCF-independent insulator that delimits X-inactivated from expressed transcripts within the UBA1 gene . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11407

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

Penn State University

12. Petro, Kimberly Anna. ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8197

► Botulinum neurotoxin serotype A (BoNT/A), one of seven serotypes of botulinum neurotoxin, is taken up by neurons of the peripheral nervous system. Within the neurons… (more)

▼ Botulinum neurotoxin serotype A (BoNT/A), one of seven serotypes of botulinum neurotoxin, is taken up by neurons of the peripheral nervous system. Within the neurons it catalyzes cleavage of the synaptosomal-associated protein having a mass of 25kDa, SNAP-25, thereby blocking neurotransmission. BoNT/A has been shown to interact with SV2, as well as gangliosides that are often found in lipid rafts. Lipid rafts are microdomains that can be found on the outer leaflet of the plasma membrane and are enriched in cholesterol and glycosphingolipids. To determine whether lipid rafts were needed for BoNT/A activity, those associated with the plasma membranes of murine N2a neuroblastoma cells were disrupted using either the cyclic oligomer methyl-β-cyclodextrin or the polyene filipin. Disruption of cholesterol containing lipid rafts by either reagent did not prevent the action of BoNT/A on murine neuroblastoma N2a cells, in fact activity was enhanced. While our results indicate that disruption of lipid rafts enhances BoNT/A activity, disruption of clathrin-dependent endocytosis appeared to be inhibitory. In addition to disruption of lipid rafts enhancing BoNT/A activity, it also induced neuritogenesis of N2a cells. Therefore, studies were performed to determine the type of process formation induced by disruption of lipid rafts by either MβCD or filipin. Because ganglioside composition has been shown to change during neuronal differentiation, the question of whether process expression was accompanied by changes in ganglioside content or subcellular distribution was addressed. The results indicate that the processes formed were axonal in nature and their expression was accompanied by changes in both ganglioside content and subcellular localization. Advisors/Committee Members: Cara Lynne Schengrund, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, Gail Lynn Matters, Committee Member, Jong Kak Yun, Committee Member, Kent Eugene Vrana, Committee Member.

Subjects/Keywords: differentiation; gangliosides; botulinum neurotoxin; membrane rafts; lipid rafts

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

APA (6^th Edition):

Petro, K. A. (2008). ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8197

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

Chicago Manual of Style (16^th Edition):

Petro, Kimberly Anna. “ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS .” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/8197.

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

MLA Handbook (7^th Edition):

Petro, Kimberly Anna. “ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS .” 2008. Web. 13 Apr 2021.

Vancouver:

Petro KA. ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/8197.

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

Council of Science Editors:

Petro KA. ROLES OF LIPID RAFTS IN BOTULINUM NEUROTOXIN SEROTYPE A ACTIVITY AND DIFFERENTIATION OF NEUROBLASTOMA CELLS . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8197

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

Penn State University

13. BANERJEE, SANJITA. MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8216

► Meprins, zinc metalloproteases of the astacin family, are composed of two independently expressed subunits meprin alpha and beta which associate to form homo and heter-oligomers,… (more)

▼ Meprins, zinc metalloproteases of the astacin family, are composed of two independently expressed subunits meprin alpha and beta which associate to form homo and heter-oligomers, termed meprin A and B. Meprin isoforms are enriched in human as well as rodent intestine. They have also been reported in kidney, leukocytes, lung and skin. Considerable research has been conducted regarding the in vitro functions of these proteases, however the physiological roles of these proteases are unknown. Generation of meprin beta, alpha and alpha-beta knock-out mice were steps towards filling this void. This work reports the general characterization of the meprin alpha knock-out mouse and investigates the role of meprin proteases in the mouse intestine using a model of colitis. Several polymorphisms have been identified in the human meprin alpha gene that significantly correlate with ulcerative colitis and Crohn’s disease, which make this mouse model relevant to the human pathology. Human and rodent intestines have high but non-uniform meprin expression and hence allow one to study the contributions of different meprin isoforms. To understand the role of meprin A, colitis was induced in wild-type and meprin alpha knock-out mice by dextran sulfate sodium administration. Meprin alpha knock-out mice showed greater susceptibility to injury and had a phenotype of heightened inflammation as evidenced by different markers of inflammation at macroscopic as well as molecular level. Further investigations showed a role for mucosal meprin A in the process of tissue repair. To understand the phenotype of increased inflammation, meprin interaction with immune-mediators was studied at greater detail. This led to the first known documentation of an in vivo interaction of meprins with an immune-mediator, interleukin–18. Subsequent experiments using meprin alpha-beta knock-out mice elucidated the contribution of meprin B in the phenotype in this model of inflammatory bowel disease. These experiments collectively demonstrated a novel function of meprins in immuno-modulation. This thesis furthers our knowledge about the roles of meprin metalloproteases in the rodent intestine and also elucidates the importance of proper distribution of meprin isoforms. Advisors/Committee Members: Judith S Bond, Committee Chair/Co-Chair, Kristin Ann Eckert, Committee Member, Sergei A Grigoryev, Committee Member, Harriet C Isom, Committee Member, Cara Lynne Schengrund, Committee Member.

Subjects/Keywords: MEPRIN; INFLAMMATORY BOWEL DISEASE

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

APA (6^th Edition):

BANERJEE, S. (2008). MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8216

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

Chicago Manual of Style (16^th Edition):

BANERJEE, SANJITA. “MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE .” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/8216.

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

MLA Handbook (7^th Edition):

BANERJEE, SANJITA. “MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE .” 2008. Web. 13 Apr 2021.

Vancouver:

BANERJEE S. MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/8216.

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

Council of Science Editors:

BANERJEE S. MEPRIN METALLOPROTEASES MODULATE INTESTINAL HOST RESPONSE . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8216

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

Penn State University

14. Hurto, Rebecca Lee. UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7136

► The goals of my research were to identify proteins involved in regulating tRNA nucleus-cytosol distribution in order to further define tRNA nucleus-cytosol trafficking and to… (more)

Subjects/Keywords: nucleus-cytosol distribution; yeast; phosphate; tRNA

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

APA (6^th Edition):

Hurto, R. L. (2008). UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7136

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

Chicago Manual of Style (16^th Edition):

Hurto, Rebecca Lee. “UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS .” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/7136.

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

MLA Handbook (7^th Edition):

Hurto, Rebecca Lee. “UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS .” 2008. Web. 13 Apr 2021.

Vancouver:

Hurto RL. UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/7136.

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

Council of Science Editors:

Hurto RL. UNCOVERING ENVIRONMENTAL AND GENETIC FACTORS INFLUENCING THE NUCLEUS-CYTOSOL DISTRIBUTION OF TRANSFER RNAS . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7136

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

Penn State University

15. Li, Nan. ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS.

Degree: 2009, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/9752

► Although most genes on one X chromosome in mammalian females are silenced by X chromosome inactivation, some genes “escape” X inactivation and are expressed from… (more)

▼ Although most genes on one X chromosome in mammalian females are silenced by X chromosome inactivation, some genes “escape” X inactivation and are expressed from both active and inactive Xs. How these escape genes are transcribed from a largely inactivated chromosome is not fully understood, but underlying genomic sequences are thought to be involved. We developed a transgene approach to ask whether an escape locus, that includes the mouse Jarid1c gene, is autonomous or is instead influenced by X chromosome location. Two BAC clones carrying Jarid1c and adjacent X-inactivated transcripts were randomly integrated into mouse XX embryonic stem cells. Four lines with single copy, X-linked transgenes were identified and we established that each integrated into regions that are normally X inactivated. As expected for genes that are normally subject to X inactivation, BAC transgene transcripts Tspyl2 and Iqsec2 were X inactivated. However, allelic expression and RNA/DNA FISH indicate that transgenic Jarid1c escapes X inactivation. Therefore, transgenes at four different locations on the X recapitulate endogenous inactive X expression patterns. We conclude that escape from X inactivation is an intrinsic feature of the Jarid1c locus and functionally delimit the Jarid1c escape domain as the 112 kb representing the maximum overlap of the BACs tested. Additionally, although extensive chromatin differences normally distinguish active and inactive loci, unmodified BACs are capable of directing proper inactive X expression patterns. Therefore, these studies establish that primary DNA sequence alone, in a chromosome position-independent manner, is sufficient to determine X chromosome inactivation status. This transgene approach will enable further dissection of key elements of escape domains and allow rigorous testing of specific genomic sequences on inactive X expression. Advisors/Committee Members: Laura Carrel, Dissertation Advisor/Co-Advisor, Laura Carrel, Committee Chair/Co-Chair, Sarah Bronson, Committee Member, Sergei A Grigoryev, Committee Member, Kent Eugene Vrana, Committee Member, Teresa L Wood, Committee Member.

Subjects/Keywords: X chromosome inactivation; epigenetics; transgene; embryonic stem cell

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

APA (6^th Edition):

Li, N. (2009). ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/9752

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

Chicago Manual of Style (16^th Edition):

Li, Nan. “ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS.” 2009. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/9752.

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

MLA Handbook (7^th Edition):

Li, Nan. “ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS.” 2009. Web. 13 Apr 2021.

Vancouver:

Li N. ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS. [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/9752.

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

Council of Science Editors:

Li N. ESCAPE FROM X CHROMOSOME INACTIVATION IS AN INTRINSIC PROPERTY OF THE MOUSE JARID1C LOCUS. [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/9752

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

Penn State University

16. Shah, Sandeep. Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/10468

► Genomic instability is a hallmark of tumor initiation and progression. A tumor genome can contain both gross chromosomal alterations as well as multiple submicroscopic nucleotide… (more)

▼ Genomic instability is a hallmark of tumor initiation and progression. A tumor genome can contain both gross chromosomal alterations as well as multiple submicroscopic nucleotide changes. Indeed, it is well established that multiple mutations are necessary for a cell to become tumorigenic. In this dissertation, I have studied two major cellular processes that, under normal circumstances, largely suppress the initial events that favor these alterations. These two processes are DNA replication, which duplicates the genome in order to fully distribute all genetic information to two daughter cells, and DNA mismatch repair, which corrects a subset of errors that occur during replication. DNA replication is an extremely accurate process where, on average, mutations occur once every 109-1010 base pairs during cell division. The central proteins for replication are DNA polymerases which travel along the template DNA while extending nascent DNA by nucleotide addition. While the vast majority of DNA is in the right-handed double helix form, many other conformations can exist within particular sequence arrangements. These non-canonical structures can impede the polymerase and stall replication until secondary mechanisms restart the process. Specific chromosomal areas have been found that are especially prone to replicative stress. These areas, termed common fragile sites (CFS), exhibit chromosomal gaps and breaks during replicative challenge and may represent a mechanism for initiating genomic instability. Chromosomal breaks are a prerequisite for alterations such as translocations, large deletions, and amplifications found in advanced tumor cells. CFS are also among the last regions to be replicated during culture of healthy untreated cells. Studies have determined that the majority of CFS are AT rich, a property believed to cause increased torsional stress and DNA secondary structure formation. This finding has lead to the hypothesis that CFS expression (breakage) may be due, in part, to stalling of the polymerase complex. Although DNA replication is a very accurate process on average, certain regions – e.g., microsatellites – have a very high error rate. Microsatellites are short, repetitive elements in the DNA consisting of 1-6 bases per repeat unit. The repetitive nature of these sequences can provoke length alterations due to strand slippage events during replication. The human DNA mismatch repair (MMR) system, a specialized repair mechanism, plays a major role in post-replicative repair of DNA polymerization errors. Loss of this pathway results in hereditary cancers characterized by microsatellite instability. In this dissertation, I first describe our studies of hPMS2, a component of MMR, and observe its role in error correction of mono-, di-, and tetranucleotide repeat motifs. Alterations at mono- and dinucleotide microsatellites have been extensively used to diagnose hereditary nonpolyposis colorectal cancer, while tetranucleotide microsatellites have been utilized for the detection of… Advisors/Committee Members: Kristin Ann Eckert, Dissertation Advisor/Co-Advisor, Kristin Ann Eckert, Committee Chair/Co-Chair, Gavin Peter Robertson, Committee Member, Sergei A Grigoryev, Committee Member, Leslie Joan Parent, Committee Member, Lisa M Shantz, Committee Member.

Subjects/Keywords: primer extension; polymerase; WRN; replication; FRA16D; PMS2; Mismatch Repair; Fragile sites; HNPCC; mutation bias

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

APA (6^th Edition):

Shah, S. (2010). Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10468

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

Chicago Manual of Style (16^th Edition):

Shah, Sandeep. “Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA .” 2010. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/10468.

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

MLA Handbook (7^th Edition):

Shah, Sandeep. “Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA .” 2010. Web. 13 Apr 2021.

Vancouver:

Shah S. Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/10468.

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

Council of Science Editors:

Shah S. Microsatellites as inducers of genome instability: Studies into the mechanisms of replication and repair of repetitive DNA . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/10468

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

Penn State University

17. Chandy, Mark. HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6926

► Chromatin condenses DNA and packages it into the nucleus. The fundamental unit of chromatin is the nucleosome, which compacts and forms higher order structures. Chromatin… (more)

▼ Chromatin condenses DNA and packages it into the nucleus. The fundamental unit of chromatin is the nucleosome, which compacts and forms higher order structures. Chromatin structure affects transcription, DNA replication and DNA repair. For gene expression, chromatin is dynamically modulated by chromatin modifying complexes and chromatin remodeling complexes. The histone code hypothesis predicts that modifications not only dictate the inheritance of chromatin states, but also that combinations of modifications recognized by protein-interaction domains are important for recruiting cofactors that alter chromatin structure. For over 40 years, histone acetylation has been associated with gene activation. Moreover, the discovery of histone acetyl transferase (HAT) complexes has implicated acetylation in transcription, DNA repair and even silencing. The SAGA complex is a 1.8 MDa multisubunit HAT complex that is recruited by activator at promoters. As the catalytic subunit of SAGA, Gcn5 acetylates promoter nucleosomes and produces a peaked acetylation profile upon gene induction. Moreover, the Gcn5 bromodomain is required for retention on acetylated nucleosomes. We test the importance of the Gcn5 bromodomain in restricting SAGA acetylation to the promoter using the scanning in vitro chromatin immunoprecipitation assay. The Gcn5 bromodomain does not significantly affect the nucleosomal acetylation profile of SAGA, even when the activator is removed from the array. While the Spt7 bromodomain does not retain SAGA on acetylated nucleosomes in vitro, its evolutionary conservation in yeast suggests that it may help retain SAGA on acetylated nucleosomes in vivo. When tested on phenotypic screens, the Spt7 bromodomain mutant and the Spt7 and Gcn5 double bromodomain mutant have a slight phenotype. The accumulation of acetylated histones at the promoter signals for the recruitment of other cofactors. SAGA and the ATP dependent chromatin remodeler, SWI/SNF functioned cooperatively in the activation of several genes in budding yeast. At the PHO5 promoter, both SAGA and SWI/SNF are important for timely removal of nucleosomes from the promoter. The loss of SWI/SNF results in the accumulation of H3K9 acetylated histones at this promoter, which is also an acetylation site for SAGA. Thus, SAGA acetylation at the promoter may recruit SWI/SNF and promote the displacement of acetylated nucleosomes. We directly test the influence of SAGA acetylation on SWI/SNF nucleosome displacement using several assays on the immobilized nucleosome array in vitro. SWI/SNF not only displaces acetylated nucleosomes, but it also targets promoter acetylated nucleosomes in the absence of activator. More important, SWI/SNF displacement of acetylated nucleosomes correlates with an increase in accessible DNA at the promoter. Advisors/Committee Members: James E Hopper, Committee Chair/Co-Chair, Sergei A Grigoryev, Committee Member, Michael G Fried, Committee Member, Laura Carrel, Committee Member, Jerry L Workman, Committee Chair/Co-Chair, Robert G Levenson, Committee Member.

Subjects/Keywords: SAGA; SWI/SNF; chromatin remodeling; bromodomain

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

APA (6^th Edition):

Chandy, M. (2008). HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6926

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

Chicago Manual of Style (16^th Edition):

Chandy, Mark. “HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES .” 2008. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/6926.

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

MLA Handbook (7^th Edition):

Chandy, Mark. “HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES .” 2008. Web. 13 Apr 2021.

Vancouver:

Chandy M. HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/6926.

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

Council of Science Editors:

Chandy M. HISTONE MODIFICATIONS INFLUENCE CHROMATIN MODIFYING AND CHROMATIN REMODELING COMPLEXES . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6926

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

Penn State University

18. Facompre, Nicole Danielle. Organoselenium-mediated alteration of prostate cancer cell signaling pathways .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11123

► Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer related death in men in the United States. The lack of… (more)

▼ Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer related death in men in the United States. The lack of treatment for “worried well” patients with prostatic intraepithelial neoplasia (a premalignant condition) combined with issues of recurrence and hormone resistance present significant obstacles to prostate cancer survivorship. The long latency of prostate cancer provides opportunity to intervene with mechanistically-based agents at various stages of disease progression. A number of signaling cascades have been shown to play important roles in prostate cancer development and progression, including the androgen receptor, PI3K/Akt, and mammalian target of rapamycin (mTOR) signaling pathways. Crosstalk between the androgen receptor and Akt pathways is thought to contribute to progression and hormone refractory disease. Studies have also implicated the mammalian target of rapamycin (mTOR) signaling pathway in the progression of prostate cancer and its transition to androgen independence, suggesting mTOR as a potential target for new therapies. Selenium, an essential nutrient and known antioxidant, has been shown in epidemiologic and preclinical studies to be protective against prostate cancer. However, clinical intervention trials with selenium have thus far had contradictory outcomes and the anti-cancer mechanisms of selenium compounds are not well understood. Studies consistently show that dose and form are critical factors in the actions of selenium compounds. In the present investigation we compare the effects of two structurally distinct organoselenium compounds naturally occurring selenomethionine (SM) and synthetic 1,4-phenylenebis(methylene)selenocyanate (p-XSC) on cell growth, apoptosis, and signaling in androgen responsive (AR) and androgen independent (AI) human prostate cancer cells. We have found that, in contrast to SM, p-XSC dose-dependently inhibits viability, induces apoptosis, and modulates critical signaling molecules in both AR and AI cells. p-XSC effectively inhibits androgen receptor expression and transcriptional activity, Akt phosphorylation, and Akt-specific phosphorylation of the androgen receptor. We also show that p-XSC preferentially inhibits mTOR complex 2 (mTORC2) signaling in AI cells, a novel potential target for selenium in prostate cancer. Based on these findings, we hypothesized that the combination of p-XSC with rapamycin, which primarily targets mTOR complex 1 (mTORC1), may be a superior approach to inhibit prostate cancer cell growth than either agent alone. Drug combination strategies can offer a number of advantages to single-agent therapies including the enhancement of efficacy, the reduction of dose and toxicity, and the management of drug resistance. Our data show that inhibition of AI cell viability and mTOR signaling is significantly enhanced by combining p-XSC and rapamycin, compared with each agent individually. We propose that these agents achieve this effect, in part, by targeting the two distinct arms of the… Advisors/Committee Members: Karam E El Bayoumy, Dissertation Advisor/Co-Advisor, Karam E El Bayoumy, Committee Chair/Co-Chair, Raghu Sinha, Committee Member, Jeffrey Maurice Peters, Committee Member, Thomas E Spratt, Committee Member, Sergei A Grigoryev, Committee Member.

Subjects/Keywords: androgen receptor; selenium; prostate cancer; Akt

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

APA (6^th Edition):

Facompre, N. D. (2010). Organoselenium-mediated alteration of prostate cancer cell signaling pathways . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11123

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

Chicago Manual of Style (16^th Edition):

Facompre, Nicole Danielle. “Organoselenium-mediated alteration of prostate cancer cell signaling pathways .” 2010. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/11123.

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

MLA Handbook (7^th Edition):

Facompre, Nicole Danielle. “Organoselenium-mediated alteration of prostate cancer cell signaling pathways .” 2010. Web. 13 Apr 2021.

Vancouver:

Facompre ND. Organoselenium-mediated alteration of prostate cancer cell signaling pathways . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/11123.

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

Council of Science Editors:

Facompre ND. Organoselenium-mediated alteration of prostate cancer cell signaling pathways . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11123

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

Penn State University

19. Tadagavadi, Raghu Kempegowda. Dendritic cells and IL-10 in nephrotoxic acute kidney injury .

Degree: 2009, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/10292

► Cisplatin is a highly effective chemotherapeutic agent used to treat a wide variety of tumors in humans. The key limitation with cisplatin therapy is nephrotoxicty… (more)

▼ Cisplatin is a highly effective chemotherapeutic agent used to treat a wide variety of tumors in humans. The key limitation with cisplatin therapy is nephrotoxicty affecting 25-35% of treated patients. Here we investigated the distribution of dendritic cells within the kidney and the role of dendritic cells and dendritic cell-produced IL-10 in cisplatin-induced acute kidney injury using a mouse model in which dendritic cells express green fluorescent protein and diphtheria toxin receptor. Dendritic cells were found interspersed between renal tubules throughout the tubulointerstitium but not in glomeruli. The functional significance of dendritic cells within their physiological context in cisplatin nephrotoxicity was examined by depleting dendritic cells using diphtheria toxin. Mice depleted of dendritic cells either before or coincident with cisplatin treatment, but not at later stages, exhibited more severe renal dysfunction, kidney tubular injury, neutrophil infiltration and greater mortality than dendritic cell non-depleted mice. Neutrophils and monocytes were abundant in the kidney at later stages of cisplatin nephrotoxicity. In contrast, infiltration of inflammatory dendritic cells was insignificant after cisplatin treatment. Through the use of bone marrow chimeric mice, we also confirmed that the exacerbated renal injury was mediated through the effect of diphtheria toxin on dendritic cells. Using mixed bone marrow chimeric mice, we showed that the worsening of cisplatin nephrotoxicity in dendritic cell-depleted mice occured independent of diphtheria toxin-mediated death of dendritic cells. Analysis of markers on renal dendritic cells after cisplatin treatment showed almost steady-state levels of expression of antigen presentation (MHC class I and MHC class II) and costimulatory molecules (CD40, CD80 and CD86), and an increase in expression of IL-10 and ICOS-L. Further investigation using mixed bone marrow chimeric mice lacking dendritic cell-derived IL-10 showed a moderate level of attenuation of kidney injury by dendritic cell-produced IL-10. These data demonstrate that dendritic cells protect mice from cisplatin nephrotoxicity. Advisors/Committee Members: Judith S Bond, Dissertation Advisor/Co-Advisor, Judith S Bond, Committee Chair/Co-Chair, W. Brian Reeves, Committee Chair/Co-Chair, Cara Lynne Schengrund, Committee Member, Sergei A Grigoryev, Committee Member, Christopher Charles Norbury, Committee Member, Robert Harold Bonneau, Committee Member.

Subjects/Keywords: dendritic cells; acute kidney injury; IL-10

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

APA (6^th Edition):

Tadagavadi, R. K. (2009). Dendritic cells and IL-10 in nephrotoxic acute kidney injury . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10292

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

Chicago Manual of Style (16^th Edition):

Tadagavadi, Raghu Kempegowda. “Dendritic cells and IL-10 in nephrotoxic acute kidney injury .” 2009. Thesis, Penn State University. Accessed April 13, 2021. https://submit-etda.libraries.psu.edu/catalog/10292.

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

MLA Handbook (7^th Edition):

Tadagavadi, Raghu Kempegowda. “Dendritic cells and IL-10 in nephrotoxic acute kidney injury .” 2009. Web. 13 Apr 2021.

Vancouver:

Tadagavadi RK. Dendritic cells and IL-10 in nephrotoxic acute kidney injury . [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Apr 13]. Available from: https://submit-etda.libraries.psu.edu/catalog/10292.

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

Council of Science Editors:

Tadagavadi RK. Dendritic cells and IL-10 in nephrotoxic acute kidney injury . [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/10292

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

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Open Access Theses and Dissertations