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The Role Of The Nascent Polypeptide-Associated Complex In Caenorhabditis Elegans, Paul T. Arsenovic
The Role Of The Nascent Polypeptide-Associated Complex In Caenorhabditis Elegans, Paul T. Arsenovic
Masters Theses, 2010-2019
The nascent polypeptide-associated complex (NAC) is a highly conserved protein complex known to play an important role in the development of metazoan organisms, but its molecular function is not well understood. Recent evidence from experiments using Saccharomyces cerevisiae as model supported the hypothesis that the NAC is either a chaperone or a component of the cytosolic chaperone network that interacts with nascent peptides emerging from the ribosome. We tested this model in C. elegans and found that the homologues of the NAC , icd-1 and icd-2, behave like chaperones in the worm. Lack of icd-1 or icd-2 altered the worms …
Chemoprevention Of Familial Melanoma, Vidhya Hariharan
Chemoprevention Of Familial Melanoma, Vidhya Hariharan
Dissertations (6 month embargo)
Bleaching agents 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH) have been known to cause occupational vitiligo This project answers whether agents 4-TBP and MBEH can be used for prophylactic treatment of familial melanoma by being specifically toxic to melanocytes and activating an immune response against distant pigment cells. Cytotoxic experiments reveal that similar to 4-TBP, MBEH induces specific melanocyte death. To compare death pathways initiated by 4-TBP and MBEH, classical apoptotic hallmarks were evaluated in treated melanocytes. MBEH induced cell death without activating the caspase cascade or DNA fragmentation, showing that the death pathway is non-apoptotic. Release …
Downregulation Of Pax2 Suppresses Ovarian Cancer Cell Growth, Huijuan Song
Downregulation Of Pax2 Suppresses Ovarian Cancer Cell Growth, Huijuan Song
Dissertations & Theses (Open Access)
PAX2 is one of nine PAX genes regulating tissue development and cellular differentiation in embryos. PAX2 promotes cell proliferation, oncogenic transformation, cell-lineage specification, migration, and survival. Unattenuated PAX2 has been found in several cancer types. We therefore sought to elucidate the role of PAX2 in ovarian carcinomas. We found that PAX2 was expressed in low-grade serous, clear cell, endometrioid and mucinous cell ovarian carcinomas, which are relatively chemoresistant compared to high grade serous ovarian carcinomas. Four ovarian cancer cell lines, RMUGL (mucinous), TOV21G (clear cell), MDAH-2774 (endometrioid) and IGROV1 (endometrioid), which express high-levels of PAX2, were used to study the …
Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female
Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female
Dissertations & Theses (Open Access)
Liposomes, also known as nontoxic, biodegradable, and non-immunogenic therapeutic delivery vehicles, have been proposed as a carrier for drugs and antitumor agents in cancer chemotherapy. Echogenic liposomes (ELIP) have the potential to entrap air or bioactive gas to enhance acoustic reflectivity in ultrasound and are used as a contrast agent. The innovative part of this study is based on a novel concept to encapsulate nitric oxide (NO) gas into ELIP, deliver it to breast cancer cells, and control its release via direct ultrasound exposure. Studies on the effect of NO in tumor biology have shown that a high levels of …
Changes In Expression Of Akt Pathway Proteins Following Treatment With Rg3 In Vitro, Kathryn Schalkoff
Changes In Expression Of Akt Pathway Proteins Following Treatment With Rg3 In Vitro, Kathryn Schalkoff
All Theses
To assess changes in AKT pathway signaling, a recombinant protein of the G3 domain of rat laminin-5 (rG3) that specifically binds the alpha subunit of integrins α6β1 and α6β4 expressed on cancer cells (e.g., MDA-MB-231) was produced. This recombinant protein is believed to interrupt the intracellular signaling events of the AKT pathway, causing a decrease in proliferation and survival of cells after treatment. Viability assays confirmed an apoptotic effect of rG3 on cells in a dose-dependent manner. However, data from gene expression studies of Caspase-9, GRB10, and CDKNIB proved non-conclusive that rG3 is acting upon gene expression, leading to the …
Nanosecond Pulsed Electric Field Induction Of Programmed Cell Death Is Cell Type Dependent: An In Vitro Study, Wei Ren
Theses and Dissertations in Biomedical Sciences
Nanosecond pulsed electric fields (nsPEFs) present a novel and effective method for cancer ablation by eradicating the ubiquitous cancer hallmark of apoptosis evasion and enforcing cancer programmed cell death. To develop nsPEFs as an anticancer method, a comprehensive understanding of cell death mechanisms is required. The overall objective of this dissertation is to elucidate molecular mechanisms underlying effects of nsPEFs on E4 murine squamous cell carcinoma and human T-cell Jurkat clones that are wildtype, deficient in FADD (ΔFADD) and deficient in caspase-8 (ACas-8). The overall hypothesis is that nsPEFs eliminate cancer cells through activating caspase-dependent and caspase-independent programmed cell death …
Dissecting The Molecular Role Of Distinct Binding Interfaces On The Retinoblastoma Tumor Suppressor In Growth Control And Tumorigenesis., Matthew J. Cecchini
Dissecting The Molecular Role Of Distinct Binding Interfaces On The Retinoblastoma Tumor Suppressor In Growth Control And Tumorigenesis., Matthew J. Cecchini
Electronic Thesis and Dissertation Repository
The retinoblastoma tumor suppressor protein (pRB) functions to maintain proliferative control and act as a barrier to tumorigenesis. pRB is capable of regulating E2F transcription factors to mediate control of proliferation through transcriptional regulation of S-phase target gene expression. In addition, pRB can stabilize the CDK inhibitor p27 through an interaction with two ubiquitin ligase complexes. Further, pRB is capable of forming a unique interaction with E2F1 termed the ‘specific’ interaction that is capable of blocking E2F1 induced apoptosis. These functions of pRB are mediated by distinct binding interfaces and their contributions to the overall functionality of pRB are not …
Study Of Cellular Activities In Response To Metal-Induced Apoptosis In Saccharomyces Cerevisiae Using Ftir, Rupa Koduru
Study Of Cellular Activities In Response To Metal-Induced Apoptosis In Saccharomyces Cerevisiae Using Ftir, Rupa Koduru
Biology Theses
Saccharomyces cerevisiae exhibits an apoptotic response upon exposure to toxic metals such as cadmium (Cd) and copper (Cu). Preliminary findings indicate that this response is dependent –to some extent- on the presence of a fermentable carbon source, glucose. To investigate this dependency we monitored the apoptotic response to both metals in the presence and absence of glucose and have shown that glucose is absolutely necessary in order to induce apoptosis in yeast at least during the exposure to metal. We have also looked at the biochemical changes that are taking place in yeast when treated with Cd using Fourier Transform …
Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma
Axogial Communication Mediated By Soluble Neuregulin-1 And Bdnf, Zhenzhong Ma
Wayne State University Dissertations
During peripheral nervous system development, successful communication between axons and glial cells including Schwann cells in peripheral nervous system and oligodendrocytes in central nervous system, is required for the proper functions of both neurons and glia. Three types of alternatively-spliced proteins belonging to the neuregulin1 (NRG1) gene family of growth and differentiation factors are essential for Schwann cell survival and peripheral nerve development. While membrane-bound NRG1 forms (type III) has been strongly implicated in the regulation of myelination process at late stage of Schwann cell development, little is known about the role of soluble, heparin-binding forms of NRG1 (type I/II) …
Novel Translational Regulation Of The Proapoptotic Bcl2 Member Puma And Its Role During Skeletal Myoblast Apoptosis, Atossa Shaltouki
Novel Translational Regulation Of The Proapoptotic Bcl2 Member Puma And Its Role During Skeletal Myoblast Apoptosis, Atossa Shaltouki
ETD Archive
Differentiation and apoptosis are coordinately regulated in skeletal myoblasts. During the process of skeletal myoblast differentiation, our lab has determined that roughly 30 of myoblasts undergo apoptosis rather than differentiation. Further, we have reported that cytochrome C is released, and that the expression level of the pro-apoptotic Bcl2 family member PUMA is elevated, when 23A2 myoblasts are cultured in DM. Our long-term goal is to identify targets for manipulation that would abrogate this apoptosis without affecting differentiation. These findings could be significant to the study of myoblast transfer as a therapeutic approach. The goals of this dissertation are to: 1- …
Dre-1/Fbxo11, A Conserved F Box Protein, Regulates Apoptosis In C. Elegans And Is Mutated In Human Lymphoma, Michael Chiorazzi
Dre-1/Fbxo11, A Conserved F Box Protein, Regulates Apoptosis In C. Elegans And Is Mutated In Human Lymphoma, Michael Chiorazzi
Student Theses and Dissertations
In the course of metazoan embryonic and post-embryonic development, more cells are generated than exist in the mature organism, and these cells are deleted by the process of programmed cell death. In addition, cells can be pushed toward death when they accumulate genetic errors, are virally-infected or are otherwise deemed potentially-harmful to the overall organism. Caenorhabditis elegans has proved to be an excellent model system for elucidating the genetic underpinnings of cell death, and research has shown that the core machinery, made up of the egl-1, ced-9, ced-4 and ced-3 genes, is conserved across metazoans, and their homologues are crucial …
Mechanisms Of Yttrium Oxide Toxicity In Hek293 Cells, Sravanthi Bodapati
Mechanisms Of Yttrium Oxide Toxicity In Hek293 Cells, Sravanthi Bodapati
Theses, Dissertations and Capstones
As a non-metal oxide, yttrium oxide (Y2O3) nanoparticles have numerous applications in chemical synthesis, mechanical polishing and as additives to drugs, cosmetics, varnishes and food. Recent data have suggested that these particles are capable of inducing oxidative stress and cytotoxicity in human endothelial cell lines. To examine the potential mechanisms of yttrium oxide toxicity, human embryonic kidney (HEK293) cells were exposed to 1, 5, 10, 50 and 100 μM of Y2O3 nanoparticles for 12, 24, 36 or 48 hr. We hypothesized that exposure of HEK293 kidney cells to Y2O3 nanoparticles would be associated with increased evidence of intracellular oxidative stress …
Biophysical Characterization Of The Membrane Binding Domain Of The Pro-Apoptotic Protein Bax, Pranav Garg
Biophysical Characterization Of The Membrane Binding Domain Of The Pro-Apoptotic Protein Bax, Pranav Garg
Electronic Theses and Dissertations
The BCL-2 family of proteins tightly regulates the delicate balance between life and death. The pore forming Bax is a pro-apoptotic member belonging to this protein family. At the onset of apoptosis, monomeric cytoplasmic Bax translocates to the outer mitochondrial membrane, forms oligomeric pores thereby letting mitochondrial cytochrome c enter the cytosol and initiate the apoptotic cascade. The C-terminal "helix 9" is thought to mediate the membrane binding of BAX. A 20-amino acid peptide corresponding to Bax C-terminus (VTIFVAGVLTASLTIWKKMG) and two mutants where the two lysines are replaced with Glu (charge reversal mutant, EE) or Leu (charge neutralization mutant, LL) …
Infection With Chlamydia Pneumoniae In Neuronal Cells Alters The Expression Of Genes Involved In Apoptosis And Autophagy Pathways, Annette K. Slutter
Infection With Chlamydia Pneumoniae In Neuronal Cells Alters The Expression Of Genes Involved In Apoptosis And Autophagy Pathways, Annette K. Slutter
PCOM Biomedical Studies Student Scholarship
Dysfunctions in cellular mechanisms such as apoptosis and autophagy have been implicated in the neurodegeneration associated with Alzheimer’s disease (AD). Autophagy in AD pathogenesis has been linked to the endosomal-lysosomal system, which has been shown to play a role in amyloid processing. Studies have suggested that apoptosis may contribute to the neuronal cell loss observed in AD; however, there is no evidence of the apoptotic process leading to terminal completion. Aβ1-42 has been shown to induce apoptosis in neurons and may be an initiating factor in AD. Our previous studies demonstrated that neurons infected with C. pneumoniae are resistant to …
The Sheddase Activity Of Adam10/Adam17 On Cxcl16 Increases Proliferation And Survival Of Colorectal Cancer Cells, Tamu C. Talton
The Sheddase Activity Of Adam10/Adam17 On Cxcl16 Increases Proliferation And Survival Of Colorectal Cancer Cells, Tamu C. Talton
Electronic Theses and Dissertations
CXCL16 is an interferon-inducible chemokine of the CXC-subfamily and functions as an adhesion molecule, when membrane bound, and a chemoattractant when soluble. Upregulation of cell associated CXCL16 (cCXCL16) in colorectal cancer is associated with increased tumor infiltrating lymphocytes and good prognosis. ADAM10 and ADAM17 are metalloproteinases responsible for cleaving CXCL16, releasing soluble CXCL16 (sCXCL16) and contributing to proliferation and migration of mesangial cells, in kidney inflammatory disease. We hypothesize that cCXCL16 is a substrate for ADAM10 and ADAM17 cleavage in colorectal cancer, releasing sCXCL16, which mediates cell proliferation. To this end, we first identified CXCL16 in the human colon carcinoma …