+publisher:"Penn State University" +contributor:("Mark Kester, Committee Member")

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Penn State University

1. Skibinski, Christine G. preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26720

► As discussed in Chapter 1, Breast cancer is the second leading cause of cancer death in women in the United States, with about 2 million… (more)

▼ As discussed in Chapter 1, Breast cancer is the second leading cause of cancer death in women in the United States, with about 2 million women at high risk for developing the disease. A current strategy, approved by the FDA, for breast cancer prevention is the daily administration of selective estrogen receptor modulators(SERMS), tamoxifen and raloxifene. These SERMS have proven to be effective at reducing breast cancer incidence in women that are at high risk by 50% and 38%, respectively. However, these agents are poorly accepted as oral chemopreventives even by women at high risk for breast cancer because of concerns of side effects which include thromboembolic events and an increase in endometrial cancers. Furthermore, both agents are ineffective against the more aggressive estrogen receptor negative tumors. A series of experiments have been conducted in our laboratories to test the hypothesis that chemoprevention can be improved by combining SERMS with agents with different mechanisms of action. Such an approach can allow the use of low doses of SERMS and thus reduce their side effects. Literature data provide some support of the protective effects of omega-3 fatty acids against the development of several cancers, including breast cancer. However, the results remain inconsistent which could be due to confounding variables. These confounding variables which have been reported by our group include omega-3:omega-6(n-3:n-6) ratio and caloric intake. A previous study conducted in our laboratories showed that high ratios of omega-3:omega-6 fatty acids(25:1 n-3:n-6) are required to inhibit mammary carcinogenesis in the rat and such high ratios of omega-3:omega-6 fatty acids potentiated the chemopreventive efficacy of tamoxifen. Studies conducted in Chapter 2 were aimed to test the hypothesis that by using a proteomics approach, novel proteins can be identified that can provide insights into the molecular mechanism by which high ratios of omega-3:omega-6 fatty acids inhibit mammary carcinogenesis. We further hypothesize that proteins identified in a minimally invasive fashion can be used for early detection and to monitor the efficacy of the chemopreventive agents. We used an isobaric Tagging for Relative and Absolute Quantitation (iTRAQ) method to provide insights into the mechanism, at the protein level, responsible for the chemopreventive action of the high omega-3:omega-6 fatty acid ratios in the absence and presence of tamoxifen in the 1-methyl-1-nitrosourea(MNU)-induced mammary tumor model in the rat; selective proteins were further validated by western blotting. Compared to control (n-3:n-6, 1:1) diet, both 10:1 and 25:1 n-3:n-6 diets upregulated plasma vitamin D binding protein, gelsolin, and 14-3-3 sigma, reported to have tumor suppressive effects, whereas alpha-1B-glycoprotein which has been reported to be elevated in the serum of breast cancer patients was decreased. Compared to 25:1 n-3:n-6, the 25:1 n-3:n-6 plus tamoxifen diet downregulated apolipoprotein E, haptoglobin, and… Advisors/Committee Members: Karam E El Bayoumy, Dissertation Advisor/Co-Advisor, Arunangshu Das, Committee Member, Thomas E Spratt, Committee Member, Andrea Manni, Committee Member, Mark Kester, Committee Member.

Subjects/Keywords: Docosahexaenoic Acid; Liposome; Breast Cancer Prevention

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APA (6^th Edition):

Skibinski, C. G. (2015). preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26720

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):

Skibinski, Christine G. “preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention.” 2015. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/26720.

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

MLA Handbook (7^th Edition):

Skibinski, Christine G. “preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention.” 2015. Web. 28 Feb 2021.

Vancouver:

Skibinski CG. preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/26720.

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

Council of Science Editors:

Skibinski CG. preclinical investigations into the role of omega-3 fatty acids for breast cancer prevention. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26720

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

Penn State University

2. Weinberg, Rebecca Bronwyn. INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12166

► Inflammatory cytokine responses play an important role in the pathogenesis of malaria. Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum are a key component in the recognition of… (more)

▼ Inflammatory cytokine responses play an important role in the pathogenesis of malaria. Glycosylphosphatidylinositols (GPIs) of Plasmodium falciparum are a key component in the recognition of the malaria parasite by the innate immune system. Macrophages respond to GPIs mainly via a Toll-like receptor 2 (TLR2) and MyD88 dependent pathway, activating signaling pathways that include the mitogen-activated protein kinases (MAPKs) and NF-κB pathways. These signaling pathways are critical for the production of cytokines that enable the immune system to respond effectively and appropriately to control the pathogen growth. The goal of the work described in this thesis was to determine the role of MAPKs and transcription factors in proinflammatory cytokine production. Two cytokines, Interleukin (IL)-12 and Tumor Necrosis Factor (TNF)-α, are of particular interest because they are involved in malaria pathogenesis and in shaping the intensity and effectiveness of the immune responses. In macrophages, the GPI- induced expression of IL-12 is controlled by an array of transcription factors. I found that IκB-zeta, a component in the NF-κB pathway, is a critical transcription factor involved in the efficient production of IL-12 in response to GPIs and other TLR ligands. Priming of cells by IFN-γ is required for optimal production of IL-12, and it appears that this mechanism does not directly overlap with the role that IκB-zeta plays in IL-12 production. Additionally, although IL-12 expression can be enhanced by suppression of certain MAPK signaling, no increase in IκB-zeta was detected using MAPK inhibitors. Thus, the MAPKs do not play a role in IL-12 production via suppression of IκB-zeta, although downstream cooperative mechanisms between these components are possible. It is well-established that TNF-α can be regulated by MAPKs at multiple levels, including transcription, mRNA stability, translation, and protein processing. The contribution of MAPK activated protein kinase 2 (MK2), a signaling molecule which plays an important role in controlling TNF-α mRNA stability, was established using bone marrow derived macrophages from Mk2-/- mice. These studies were performed with TLR ligands using pharmacological inhibitors to analyze the MAPKs responsible for activating MK2. In addition to the known role for p38 in activation of MK2, I observed a role for the ERK1/2 MAPK in its regulation. Time-course studies provided new insights into temporal modulation of MK2 activation by different MAPK pathways. The effects of MK2 on TNF-α mRNA stability are believed to be related to a target of MK2, tristetraprolin (TTP) that binds the TNF-α mRNA. I confirmed that the Mk2-/- mice were impaired in their activation of TTP. In addition, I discovered a new role for the Tpl2/ERK1/2 MAPK pathway in the regulation of the protein TTP. Collectively, these results provide detailed mechanistic insights into how the innate immune system responses to the recognition of malaria parasite GPIs. The data… Advisors/Committee Members: Channe D Gowda, Dissertation Advisor/Co-Advisor, Channe D Gowda, Committee Chair/Co-Chair, Jong Kak Yun, Committee Member, Mark Kester, Committee Member, Pamela Hankey Giblin, Committee Member, Todd Schell, Committee Member, Cara Lynne Schengrund, Committee Member.

Subjects/Keywords: malaria; innate immunity; cytokines; signal transduction; macrophages

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

APA (6^th Edition):

Weinberg, R. B. (2011). INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12166

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):

Weinberg, Rebecca Bronwyn. “INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS.” 2011. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/12166.

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

MLA Handbook (7^th Edition):

Weinberg, Rebecca Bronwyn. “INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS.” 2011. Web. 28 Feb 2021.

Vancouver:

Weinberg RB. INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/12166.

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

Council of Science Editors:

Weinberg RB. INFLAMMATORY CYTOKINE RESPONSES TO MALARIA PARASITE GLYCOSYLPHOSPHATIDYLINOSITOLS. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12166

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

Penn State University

3. Gao, Guofeng. REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7430

► Transforming growth factor ? (TGF?) is the prototype for a superfamily of related members. TGF? family signaling controls various fundamental cellular functions, including cell proliferation… (more)

▼ Transforming growth factor ? (TGF?) is the prototype for a superfamily of related members. TGF? family signaling controls various fundamental cellular functions, including cell proliferation and migration. Alterations in the TGF? signaling pathways have been implicated in a vast array of human cancers and other diseases as well. Despite advances in our understanding of TGF? signaling transduction, the mechanism of the multifunctional TGF? signaling is not completely clear yet. Therefore, further studies are required for deeper understanding of its diverse biological responses. DYNLRB1 was identified in the laboratory through a screen for TGF? receptor-interacting proteins, and it is also a dynein light chain. Dynein is molecular motor that plays many important functions in the cell. I hypothesized that DYNLRB family dynein light chains may play important specific functions in TGF? signaling. In this thesis, we investigated the regulation of the function of DYNLRB dynein light chains by TGF? and their role in TGF? signaling in mammalian cells and in primary zebrafish (Danio rerio) ovarian follicle cells. The experiments in Chapter 2 aimed to determine the involvement of DYNLRB1 in TGF? signaling and characterizing the function of DYNLRB1. The results from this chapter have demonstrated that the phosphorylation of DYNLRB1 on serine residues is stimulated by TGF? in Cos-1 cells and requires T?RII. It is further demonstrated that DYNLRB1 expression knockdown significantly impaired TGF?-induced fibronectin expression in MDCK cells. TGF?-induced DYNLRB1phosphorylation has been shown to be responsible for its recruitment to the dynein motor complex. Therefore, these results indicate a potential role for DYNLRB1 as a TGF? signaling intermediate, and its requirement in TGF? induction of fibronectin (a major component of the extracellular matrix), which plays important roles in cell adhesion, migration and differentiation. The experiments in Chapter 3 was designed to test the hypothesis that DYNLRB2 might be involved in Smad3-dependent TGF? signaling. Human DYNLRB2 is 77% identical to human DYNLRB1. Results in Chapter 3 have demonstrated that TGF? induction of SBE2-Luc, plasminogen activator inhibitor-1 expression in HaCaT cells and of Smad7-Luc in Hep3B cells, is significantly impaired, after blocking endogenous DYNLRB2 expression by siRNA. It is known that the induction of these genes is Smad3-dependent signaling event. However, similar blocking of DYNLRB2 expression does not inhibit the induction of ARE-Lux by TGF?, which has been demonstrated to be Smad2-dependent signaling event. Therefore, these results suggest that DYNLRB2 is specifically required in Smad3-dependent signaling. Further, it is demonstrated that TGF?-stimulated preferential interaction between DYNLRB2 and Smad3 may be the underlying mechanism for the requirement of DYNLRB2 in Smad3-dependent TGF? signaling. In addition, results have shown that TGF? stimulated a rapid recruitment of the DYNLRB2 to the dynein complex, and the… Advisors/Committee Members: Sarah Bronson, Committee Chair/Co-Chair, Keith C Cheng, Committee Member, Mark Kester, Committee Member, Jiyue Zhu, Committee Member.

Subjects/Keywords: DYNLRB; dynein light chain; TGFbeta

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

APA (6^th Edition):

Gao, G. (2008). REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7430

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):

Gao, Guofeng. “REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING .” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/7430.

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

MLA Handbook (7^th Edition):

Gao, Guofeng. “REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING .” 2008. Web. 28 Feb 2021.

Vancouver:

Gao G. REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/7430.

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

Council of Science Editors:

Gao G. REQUIREMENT OF THE DYNLRB FAMILY DYNEIN LIGHT CHAINS IN TRANSFORMING GROWTH FACTOR BETA SIGNALING . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7430

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

Penn State University

4. Altinoglu, Erhan I. Indocyanine Green-Encapsulating Calcium Phosphosilicate Nanoparticles: Bifunctional Theranostic Vectors for Near Infrared Diagnostic Imaging and Photodynamic Therapy .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11060

► The American Cancer Society projected 1.5 million new cancer cases to be diagnosed in 2009. Of these diagnoses, a mere 20% were expected to be… (more)

▼ The American Cancer Society projected 1.5 million new cancer cases to be diagnosed in 2009. Of these diagnoses, a mere 20% were expected to be detected in their early, localized stage. With such advantageous early detection comes various low risk and highly effective treatment options, resulting in 5-year relative survival rates of over 90%. Unfortunately, the remaining diagnoses were expected in a later stage of the progressive disease, where treatment requires infusions of toxic pharmaceuticals and blasts of brutal radiation, and the prognosis is as miserable as the experience itself. Thus, the advantages associated with timely detection and treatment has generated interest in a simultaneous approach to early diagnosis and therapy, a combined modality termed theranostics. Recently, the concept of multifunctional nanocarriers that can concurrently perform these distinct tasks has emerged and is attracting increased attention. The full potential of a theranostic strategy lies in the ability to engineer such a bifunctional vector with both of the optical and therapeutic properties necessary to complete the separate functions. Specifically, much interest has been initiated on fluorescent photosensitive agents that respond in the near infrared (NIR) by concurrently emitting intense and sustained fluorescence signals for deep tissue imaging, as well as generating a photodynamic response to trigger localized cell death for minimally invasive, molecular-scale therapy. The synthesis, laundering, and properties of calcium phosphosilicate nanoparticles (CPSNPs) that encapsulate the NIR fluorophore indocyanine green (ICG) related to multifunctional fluorescent photosensitization is presented. Imaging with transmission electron microscopy (TEM) revealed the well dispersed state of the nanoparticles, the spherical morphology, and the log normal mean particle diameter of 16 nm. Electron energy loss spectroscopy (EELS) mapping identified a Ca:P:Si ratio of 1:1.72:0.41 and a homogeneous composition without evidence of an element rich or deficient architecture. Zeta potential of the as-synthesized, citrate-functionalized CPSNPs was -29 ±3 mV. A theoretical solids loading of 1.9 x 1013 CPSNP/mL was calculated for a standard suspension. The mean ICG content per suspension is 2 x 10-6 M, which equates to approximately 63 fluorophore molecules encapsulated per CPSNP. For imaging and diagnostic considerations, the doped CPSNPs exhibited significantly greater intensity at the maximum emission wavelength relative to the free constituent fluorophore. The quantum efficiency of the fluorescent agent is 200% greater at 0.053±0.003 over the free fluorophore in PBS. Also, photostability based on fluorescence half-life of encapsulated ICG in PBS is 500% longer under typical clinical imaging conditions relative to the free dye. These performance enhancements are attributed to the matrix shielding effect of the NP around the internalized fluorophore molecules. The in vivo emission signal stability from ICG-CPSNPs was compared to the free… Advisors/Committee Members: James Hansell Adair, Dissertation Advisor/Co-Advisor, James Hansell Adair, Committee Chair/Co-Chair, Mark Kester, Committee Member, Carlo G Pantano, Committee Member, Gary Lynn Messing, Committee Member.

Subjects/Keywords: photodynamic therapy; diagnostic imaging; near infrared; encapsulation; nanoparticles; indocyanine green; calcium phosphate

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APA (6^th Edition):

Altinoglu, E. I. (2010). Indocyanine Green-Encapsulating Calcium Phosphosilicate Nanoparticles: Bifunctional Theranostic Vectors for Near Infrared Diagnostic Imaging and Photodynamic Therapy . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11060

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):

Altinoglu, Erhan I. “Indocyanine Green-Encapsulating Calcium Phosphosilicate Nanoparticles: Bifunctional Theranostic Vectors for Near Infrared Diagnostic Imaging and Photodynamic Therapy .” 2010. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/11060.

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

MLA Handbook (7^th Edition):

Vancouver:

Altinoglu EI. Indocyanine Green-Encapsulating Calcium Phosphosilicate Nanoparticles: Bifunctional Theranostic Vectors for Near Infrared Diagnostic Imaging and Photodynamic Therapy . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/11060.

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

Council of Science Editors:

Altinoglu EI. Indocyanine Green-Encapsulating Calcium Phosphosilicate Nanoparticles: Bifunctional Theranostic Vectors for Near Infrared Diagnostic Imaging and Photodynamic Therapy . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11060

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

Penn State University

5. Poole, Brian Douglas. PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6347

► ABSTRACT Parvovirus B19 persists in multiple tissues and has been implicated in a variety of diseases including acute fulminant liver failure (AFLF). Despite multiple reports… (more)

▼ ABSTRACT Parvovirus B19 persists in multiple tissues and has been implicated in a variety of diseases including acute fulminant liver failure (AFLF). Despite multiple reports demonstrating the presence of B19 DNA in liver tissues from patients with AFLF, the causal relationship of B19 infection to liver failure is not yet proven. In addition, the mechanism by which B19 infection induces liver failure remains unknown. Although hepatocytes express the B19 receptor, globoside, these cells are non-permissive for B19 replication. B19, although unable to replicate productively in liver cells, may establish a limited infection that kills these cells. B19 cytotoxicity is likely mediated through the viral nonstructural protein, NS1. The NS1 protein has the potential to damage cellular DNA through DNA nicking, covalent DNA binding, and helicase activities. We hypothesize that DNA damage induced by these activities leads to apoptosis through PARP and ATR-mediated pathways. To investigate whether B19 is able to establish infection of hepatocytes, both primary liver cells and the hepatocellular carcinoma cell line Hep G2 were inoculated with parvovirus B19 and examined for the presence of RNA transcripts of viral genes. RT-PCR analysis demonstrated that B19 was able to infect both primary and transformed hepatocytes and produce RNA for NS1. No transcripts correlating to the structural capsid proteins VP1 or VP2 were detected. Immunofluorescence-based studies confirmed the presence of NS1 in infected cells. These experiments demonstrate that B19 enters liver cells, and that the NS1 gene is actively transcribed and the mRNA is translated in infected hepatocytes. The ability of B19 to infect hepatocytes allows for the possibility that B19 infection of these cells is cytotoxic. Pathological studies of tissue from patients with AFLF are characterized by non-inflammatory hepatocellular death. Non-inflammatory disappearance of hepatocytes suggests apoptosis as the mechanism for B19-induced cell death in AFLF. To investigate whether B19 induces apoptosis in liver cells, hepatocytes and Hep G2 cells were infected and assayed for apoptosis by PARP cleavage assays and annexin-V staining. Infection with B19 led to PARP cleavage and induced apoptosis, with a mean of 28% of infected Hep G2 cells and 24% of infected primary hepatocytes undergoing apoptosis as determined by annexin-V staining, compared to 7% apoptosis in mock-infected cells. Several lines of evidence suggest that NS1 is the molecule responsible for the B19-induced apoptosis of liver cells. Irradiated virions, which are incapable of having their genes transcribed, do not induce apoptosis, suggesting that transcription is requisite for B19-induced apoptosis. Since NS1 is the only known transcript produced by B19 infection of hepatocytes, it is likely that NS1 is the apoptosis-inducing factor. Apoptosis can proceed through many different mechanisms. These pathways are regulated by the involvement of different caspases, cysteine proteases that mediate… Advisors/Committee Members: Stanley J Naides, Committee Chair/Co-Chair, Robert Harold Bonneau, Committee Member, Sarah Bronson, Committee Member, Michael J Chorney, Committee Member, Mark Kester, Committee Member.

Subjects/Keywords: parvovirus B19; Apoptosis; Acute fulminant liver failure; DNA damage

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

APA (6^th Edition):

Poole, B. D. (2008). PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6347

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):

Poole, Brian Douglas. “PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS.” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/6347.

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

MLA Handbook (7^th Edition):

Poole, Brian Douglas. “PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS.” 2008. Web. 28 Feb 2021.

Vancouver:

Poole BD. PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/6347.

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

Council of Science Editors:

Poole BD. PARVOVIRUS B19 INFECTION OF HEPATOCYTES AND INDUCTION OF APOPTOSIS. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6347

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

Penn State University

6. Blome, Matthew. CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8208

► Ricin toxin is a potent type 2 ribosome inactivating protein (RIP) from the plant, Ricinus communis. It has the potential to be used as a… (more)

▼ Ricin toxin is a potent type 2 ribosome inactivating protein (RIP) from the plant, Ricinus communis. It has the potential to be used as a bioterrorism agent due to its high toxicity and the relative ease with which it can be obtained/purified. Ricin is a heterodimeric protein consisting of 2 subunits. The A-chain (RTA) is an N-glycosidase that halts protein synthesis by catalyzing the depurination of a specific adenine residue on ribosomal RNA. RTA is linked to the B-chain (RTB) via a single disulphide bridge. RTB is a lectin, containing 2 galactose binding sites ~70Å apart, that plays an essential role in mediating the binding and internalization of the toxin. While the binding of ricin to galactose has been studied, characterization of the binding of ricin to more complex carbohydrate ligands (i.e., glycoproteins and glycolipids) that might be present on the surface of a cell is lacking. In contrast to the low affinity of RTB for monovalent galactose (reported to be between 0.28 and 3.5x 10-4M), its affinity for asialofetuin (ASF) is about 1,000 times greater than it is to monovalent galactose. This observation supports the hypothesis that ricin exhibits multivalency when it adheres to ASF. The goal of this work was to synthesize multivalent carbohydrate ligands, use them to determine whether ricin would bind to them in a multivalent fashion, and to identify general saccharide characteristics that affect binding. To account for the distance between the two galactose binding sites on RTB, bovine serum albumin (BSA) was selected as the oligosaccharide carrier. BSA-based neoglycoconjugates were synthesized and their efficacy as ligands for the toxin monitored using surface plasmon resonance (SPR). The results indicated that ricin did exhibit multivalency when it interacted with appropriately derivatized BSA neoglycoconjugates and that it appeared to bind more efficiently to specific longer chain oligosaccharide ligands than to disaccharides. These observations have important implications for the development of possible antidotes for the treatment of people inadvertently exposed to ricin, for the use of RTB in drug deliver, and for optimization of ricin biosensors. Advisors/Committee Members: Cara Lynne Schengrund, Committee Chair/Co-Chair, Ira Joseph Ropson, Committee Member, Thomas E Spratt, Committee Member, Mark Kester, Committee Member, Michael Pishko, Committee Member.

Subjects/Keywords: glycoconjugate; asialofetuin; surface plasmon resonance; asialo-GM1; ricin; bovine serum albumin; multivalent

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

APA (6^th Edition):

Blome, M. (2008). CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8208

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):

Blome, Matthew. “CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES .” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/8208.

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

MLA Handbook (7^th Edition):

Blome, Matthew. “CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES .” 2008. Web. 28 Feb 2021.

Vancouver:

Blome M. CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/8208.

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

Council of Science Editors:

Blome M. CHARACTERIZATION OF RICIN BINDING TO MULTIVALENT BOVINE SERUM ALBUMIN-BASED NEOGLYCOCONJUGATES . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8208

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

Penn State University

7. Francy, Jacquelyn M. Mechanistic studies of sphingosine kinase 1 localization and activation .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7296

► Sphingosine kinase 1 (SphK1) is an indispensable signaling molecule involved in cellular proliferative and anti-apoptotic signaling. There is a large body of evidence that SphK1… (more)

▼ Sphingosine kinase 1 (SphK1) is an indispensable signaling molecule involved in cellular proliferative and anti-apoptotic signaling. There is a large body of evidence that SphK1 levels are elevated in hyperproliferative diseases, such as cancer and atherosclerosis, making SphK1 a novel therapeutic target for limiting aberrant cellular proliferation. Development of pharmacological inhibitors of SphK1 has been limited by the lack of understanding of the mechanisms of enzymatic activation of SphK1, which has been shown to occur in a biphasic manner. Early phase activation takes place in a matter of minutes. It is believed that following stimulation, basally active cytosolic SphK1 translocates to the plasma membrane, where it is further activated by lipid and/or protein cofactors, resulting in a transiently inducible SphK1 activation. Late phase activation occurs over the course of hours through transcriptional and translational upregulation of SphK1 expression. The goal of this study is to investigate mechanisms of early and late phase activation of SphK1. We demonstrate that growth factor stimulation results in a transient accumulation of highly active SphK1 in a distinct plasma membrane microdomain, the membrane raft. We show that a pool of SphK1 as well as its substrate, sphingosine, reside in membrane rafts by using differential centrifugation and sucrose density gradient centrifugation techniques. This population of SphK1 exhibited a high specific catalytic activity and was depleted from membrane rafts in cells that had been treated with cholesterol binding agents that disrupt membrane raft integrity. We further show that following FBS stimulation, SphK1 protein levels at the membrane raft are increased. This increase coincided with a decrease in membrane raft sphingosine levels and an increase in sphingosine-1-phosphate (S-1-P) in the intracellular and extracellular space. We observed a colocalization of SphK1 with the membrane raft marker GM-1 by confocal microscopy, particularly at the leading edge of HEK293 cells. Together, these data provide strong evidence that membrane rafts are sites for temporally and spatially controlled induction of SphK1 activity, which has implications in compartmentalization of S-1-P signaling at particular cellular locales, such as the leading edge of a migrating cell. We demonstrate that SphK1 is necessary for proliferation of human coronary artery smooth muscle (HCASM) cells. Our results demonstrate that PDGF stimulation results in increased SphK1 mRNA levels within 3 h, followed by an increase in SphK1 protein synthesis and enzymatic activity that is observed 8 - 24 h later. Using a panel of pharmacological inhibitors, we identified the PI3K/AKT/mTOR pathway as a key regulator of late phase SphK1 activation involving transcriptional/translational upregulation. Utilizing isoform-specific siRNA for each isoform of AKT (AKT1, AKT2, AKT3), we identified that AKT2 was necessary for an increase in SphK1 mRNA, protein, and activity levels following PDGF… Advisors/Committee Members: Jong Kak Yun, Committee Chair/Co-Chair, Mark Kester, Committee Member, Kristin Ann Eckert, Committee Member, Cara Lynne Schengrund, Committee Member, Melvin Lee Billingsley, Committee Member.

Subjects/Keywords: plasma membrane; membrane raft; sphingosine kinase; sphingosine; AKT2

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

APA (6^th Edition):

Francy, J. M. (2008). Mechanistic studies of sphingosine kinase 1 localization and activation . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7296

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):

Francy, Jacquelyn M. “Mechanistic studies of sphingosine kinase 1 localization and activation .” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/7296.

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

MLA Handbook (7^th Edition):

Francy, Jacquelyn M. “Mechanistic studies of sphingosine kinase 1 localization and activation .” 2008. Web. 28 Feb 2021.

Vancouver:

Francy JM. Mechanistic studies of sphingosine kinase 1 localization and activation . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/7296.

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

Council of Science Editors:

Francy JM. Mechanistic studies of sphingosine kinase 1 localization and activation . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7296

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

Penn State University

8. Romanelli, Robert John. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7191

► Previously we demonstrated that IGF-I mediates long-term survival of oligodendrocyte progenitors (OPs) via sustained phosphorylation and activity of Akt, with concomitant stability and activity of… (more)

▼ Previously we demonstrated that IGF-I mediates long-term survival of oligodendrocyte progenitors (OPs) via sustained phosphorylation and activity of Akt, with concomitant stability and activity of the IGF type-I receptor (IGF-IR). The mechanism by which IGF-I regulates signal transduction, however, is currently undefined. In this dissertation, we investigate the role of IGF-IR trafficking and subcellular localization in sustained Akt phosphorylation in OPs. We report the loss of IGF-IRs from the cell surface, with subsequent recovery during IGF-I stimulation. Using multiple pharmacological inhibitors of receptor trafficking we show that cluster and internalization of the IGF-IR is required to promote Akt phosphorylation and that recycling is required to sustain Akt phosphorylation. We also show that the IGF-IR co-localizes with recycling endosome markers, including the transferrin receptor and rab11, further suggesting a role for IGF-IR recycling. Mathematical analyses predict a model of receptor trafficking consistent with our empirical data of sustained Akt phosphorylation through 120 min. We also report that integrity of cholesterol/glycosphingolipid-enriched membrane microdomains (CEMs), also known as lipid rafts, is required to promote IGF-I mediated Akt phosphorylation. Based on these findings, we propose that the IGF-IR and its signaling proteins are localized within CEMs. Membrane extraction with triton or sodium carbonate yield CEMs from OPs containing the classical rafting proteins caveolin-1 and flotillin-1. Furthermore, the IGF-IR and PI-3K/Akt signaling proteins co-localize in these microdomains We were further interested in determining the role of caveolae, a subset of lipid rafts that contain the protein caveolin-1, in OL biology. We report that caveolin-1 protein expression increased during OL maturation. Additionally, caveolin-1 localization within CEMs correlates with IGF-I stimulation. We also show that the IGF-IR co-localizes with caveolin-1 at a stage of OL maturation when caveolin-1 is maximally expressed, and that the IGF-IR contains a caveolin binding motif that is conserved through evolution. Analysis of brains from caveolin-1 knockout mice reveals aberrant expression of myelin- and OL-specific proteins. The results of this dissertation support our hypothesis that IGF-IR trafficking and localization mediate the sustained phosphorylation of Akt in OPs, and elucidates a role for membrane microdomains in the regulation of IGF-I signaling. Advisors/Committee Members: Teresa Wood, Committee Chair/Co-Chair, Sarah Bronson, Committee Chair/Co-Chair, Steve Levison, Committee Member, Mark Kester, Committee Member, Shao Cong Sun, Committee Chair/Co-Chair.

Subjects/Keywords: oligodendrocytes; Akt; signal transduction; IGF-I; lipid rafts; caveolin; receptor trafficking

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

APA (6^th Edition):

Romanelli, R. J. (2008). IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7191

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):

Romanelli, Robert John. “IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/7191.

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

MLA Handbook (7^th Edition):

Romanelli, Robert John. “IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY .” 2008. Web. 28 Feb 2021.

Vancouver:

Romanelli RJ. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/7191.

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

Council of Science Editors:

Romanelli RJ. IGF TYPE I RECEPTOR LOCALIZATION AND TRAFFICKING IN OLIGODENDROCYTE PROGENITOR CELLS: REGULATION OF THE PI-3 KINASE/AKT PATHWAY . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7191

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

Penn State University

9. Ackermann, Joseph Michael. NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6533

► Ornithine decarboxylase (ODC) is known to have an important role in cell transformation, but that role is not well understood. The scientific and clinical value… (more)

▼ Ornithine decarboxylase (ODC) is known to have an important role in cell transformation, but that role is not well understood. The scientific and clinical value of reducing the activity of ODC, a key enzyme in the biosynthesis of polyamines, is well appreciated. Polyamines are necessary components for cell growth and manipulation of polyamine homeostasis may be an effective strategy for the treatment of a number of disorders, including neoplastic diseases. Indeed, -difluoromethylornithine (DFMO), a specific enzyme-activated irreversible inhibitor of ODC is currently in clinical trials as a potential chemopreventative/therapeutic agent and is clinically used for other disorders. However, the effectiveness of DFMO is limited by the drug's pharmacokinetic profile and the unique regulation of ODC. Targeting ODC mRNA may be an effective method to reduce ODC activity due to the enzyme's extensive regulation at the translational and protein levels. The half-life of ODC is among the shortest of any known protein. Due to the rapid turnover of ODC protein, cells are reliant on translation of new protein to maintain or elevate ODC activity. A number of reports have indicated that little to no change in ODC mRNA content is often detected upon substantial increases or decreases in ODC protein content and activity. Reversible inhibitors of ODC protein have a disadvantage because they can stabilize ODC from degradation. The initial inhibition of ODC leads to increased ODC transcription and active ODC can accumulate in the cells. Conversely, the efficacy of irreversible inhibitors may be limited by the short half-life of ODC. Therefore targeting ODC mRNA, rather than protein, may be a better strategy. An approach to develop an effective 10-23 DNAzyme and hammerhead ribozyme against ODC is described in these studies. DNAzymes and ribozymes bind to a cognate RNA substrate via Watson-Crick base pairing hybridization arms and subsequently catalyze cleavage of a phosphodiester bond of the RNA. The major difference between the two is the base composition; DNAzymes are composed of DNA, ribozymes of RNA. DNAzymes capable of cleaving the target ODC RNA were identified in vitro and further characterized by the effect each had on ODC protein and activity levels using in vitro translated ODC RNA. ODC protein levels and activity correlated well with the RNA cleavage activity of the DNAzyme. A DNAzymes that exhibited good activity was optimized for use in cell culture studies. The length of the DNAzyme hybridization arms was altered and kinetics were performed to identify the most catalytically efficient configuration. One DNAzyme, DZ IV, with equal length arms of nine nucleotides proved to be the most catalytically efficient. In HEK 293 cells, DZ IV was able to reduce the amount of translated ODC protein resulting in ~80% reduction in ODC activity—a statistically significant enhancement over the antisense effect of a catalytically inactive DNAzyme. The effectiveness of DZ IV was evaluated an in vivo model with clinical… Advisors/Committee Members: Anthony Edward Pegg, Committee Chair/Co-Chair, Melvin Lee Billingsley, Committee Member, Mark Kester, Committee Member, Lisa M Shantz, Committee Member, Charles D Smith, Committee Member, Kent Eugene Vrana, Committee Member.

Subjects/Keywords: polyamines; ornithine decarboxylase; gene silencing; DNazyme; ribozyme; antisense oligodeoxynucleotides; difluoromethylornithine; DFMO; resonance energy transfer; RET; FRET; catalytic nuleic acids

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

APA (6^th Edition):

Ackermann, J. M. (2008). NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6533

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):

Ackermann, Joseph Michael. “NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION.” 2008. Thesis, Penn State University. Accessed February 28, 2021. https://submit-etda.libraries.psu.edu/catalog/6533.

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

MLA Handbook (7^th Edition):

Ackermann, Joseph Michael. “NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION.” 2008. Web. 28 Feb 2021.

Vancouver:

Ackermann JM. NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Feb 28]. Available from: https://submit-etda.libraries.psu.edu/catalog/6533.

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

Council of Science Editors:

Ackermann JM. NOVEL APPROACHES TO MODULATE ORNITHINE DECARBOXYLASE ACTIVITY AND TO DETERMINE A ROLE FOR ORNITHINE DECARBOXYLASE IN CELL TRANSFORMATION. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6533

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