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Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez Jan 2024

Streptozotocin-Induced Diabetes Increases Kidney Toxicity In Rats Exposed To Ochratoxin A, Belkys Gonzalez

Theses and Dissertations

Due to the rising occurrence of diabetes in the population and the prevalence of OTA exposure via ingestion of contaminated foodstuffs, there is a need to assess the possible renal interaction of a diabetic disease state in concurrence with OTA exposure. Sprague Dawley rats were treated with streptozotocin to induce experimental diabetes and then orally exposed to 0.5 mg/kg body weight OTA once a day for 21 days. Renal biomarkers and light microscopy were evaluated to assess the interaction between diabetic nephropathy and OTA exposure. LLC-PK1 proximal tubule cells were used as an in vitro model to assess the potential …


Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos Jan 2024

Evaluation Of Microglia’S Structural Variations Within An Organotypic Hippocampal Slice Model After Regionalized Toxic Injury, Jesus Antonio Trejos

Theses and Dissertations

The dendritic cells of the CNS, the microglia (MG), are an initiation point of the immunological response within the post blood-brain barrier (BBB) compartment. Microglia morphology drastically changes in response to cell stress to a much different non-dendritic morphology. This investigation postulates that if the first MG responses to toxic injury are isolated and studied in greater morphological detail there is much to be learned about MG metamorphosis from a baseline (M2) to an activated (M1) state. The organotypic hippocampal slice was the experimental setting used to investigate microglial response to toxic injury. This isolates dendritic cellular responses and associated …


Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid Jan 2024

Combined Cytotoxicity Of The Herbicide Glyphosate And The Fungicide Mancozeb In Mouse Neuroblastoma Cells, Heidi Ebid

Theses and Dissertations

The herbicide glyphosate and the fungicide mancozeb are globally applied on a variety of agricultural crops. Residues of both pesticides are frequently detected in food and water. Combined exposure to both compounds is therefore possible. Glyphosate and mancozeb have been separately investigated in previous studies and were shown to induce neurotoxicity. The current study investigates the cytotoxicity of different glyphosate and mancozeb combinations including mixture of mancozeb + glyphosate, combination of mancozeb followed by glyphosate and combination of glyphosate followed by mancozeb and compares neurotoxicity seen with the combinations to that of glyphosate or mancozeb using mouse neuroblastoma Neuro-2a cells. …


Exposure To Dithiocarbamate Fungicide Ziram Results In Hepatic And Renal Toxicity In Long-Evan Rats, Jeffrey Chen Jan 2024

Exposure To Dithiocarbamate Fungicide Ziram Results In Hepatic And Renal Toxicity In Long-Evan Rats, Jeffrey Chen

Theses and Dissertations

Ziram is a broad spectrum fungicide that is used on a variety of crops. It has been shown to display a wide array of toxicological effects, however, there is still a scarcity of mechanistic data regarding how it facilitates those effects. One of its presumed mechanisms of toxicity is due to the production of oxidative stress. However, whether the production of oxidative stress is due to its dimethyldithiocarbamate backbone, its metal moiety, or a combination of both, is still unknown. Contributing to the production of oxidative stress is ziram’s ability to alter essential metal homeostasis through transchelation of other essential …


Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu Jan 2024

Production Of Vp3-Only Aav2 Vlp In E. Coli, Chengyu Fu

Theses and Dissertations

Adeno-associated virus (AAV) is a widely used vector for gene therapy. However, few studies have focused on producing AAV-based virus-like particles (VLP) in E. coli. This project aimed to express VP3 of AAV2 or co-express VP3 of AAV2 with other proteins, such as E. coli chaperones and/or assembly-activating protein (AAP) in E. coli under different expression conditions and explore the potential to produce VP3-only VLP of AAV2 in situ in E. coli. The constructed plasmid pET15ΔHis-VP3 was used to express VP3 under different conditions. The results demonstrated that most expressed VP3 was in inclusion bodies in all tested conditions. Although …


Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli Jan 2024

Determination Of Genetic Variation In Opioid-Resistant Hospice Patients Using A Pharmacogenomics Approach, Daniel Bianculli

Theses and Dissertations

Managing pain requires a delicate balance between the advantages of opioid analgesia and the possible adverse effects. This balance becomes even more difficult in hospice and palliative care environments where dosage regimens are frequently ambiguous. Some hospice patients experience opioid resistance, in which opioids no longer produce an analgesic effect on a patient. Evidence-based analyses frequently omit this vulnerable population, resulting in a need for concrete procedures. The emergence of pharmacogenomic analysis and personalized treatment presents a solution to this problem by using each patient's genomic data to interpret opiate dosing. This pharmacogenomic study aimed to single nucleotide polymorphisms (SNPs) …


Symbiosis Under Stress: Unraveling The Interplay Of Ocean Acidification And Rising Temperatures On Acropora Samoensis (Staghorn Coral), Jerald William Smolkin Jan 2024

Symbiosis Under Stress: Unraveling The Interplay Of Ocean Acidification And Rising Temperatures On Acropora Samoensis (Staghorn Coral), Jerald William Smolkin

Theses and Dissertations

This experiment explores the response of marine organisms to the combined challenges of ocean acidification and rising temperatures, with a focus on coral reef ecosystems. As global climate change threatens profound declines in coral reefs, understanding the multifaceted impacts of these stressors becomes crucial. The study observes cellular changes in A. samoensis tissues in four different groups, including control, Temp, pH, and Temp and pH. Results indicate significant breakdown of membrane compartmentalization and cell junctions, with notable degradation and calcium carbonate crystallization in pH-stressed samples. Additionally, chlorophyll extraction data support coral bleaching due to the expulsion of zooxanthellae. These findings …


Hydroxyurea Globally Inhibits Rna Synthesis, Destabilizes Mrnas, And Triggers Mec1-Opposed Rnapii Accumulation At 3’ Ends Of Genes, Pritpal Kaur Jan 2023

Hydroxyurea Globally Inhibits Rna Synthesis, Destabilizes Mrnas, And Triggers Mec1-Opposed Rnapii Accumulation At 3’ Ends Of Genes, Pritpal Kaur

Theses and Dissertations

My dissertation includes two projects. The first project is focused on the regulation of glycolysis and oxidative metabolism by inducing heme synthesis in cancer cells. The second project deals with the effect of hydroxyurea on RNA synthesis. Heme is an essential cofactor for enzymes of the electron transport chain (ETC) and ATP synthesis in mitochondrial oxidative phosphorylation (OXPHOS). Heme also binds to and destabilizes Bach1, a transcription regulator that controls expression of several groups of genes important for glycolysis, ETC, and metastasis of cancer cells. Since many cancers are characterized by a high glycolytic rate regardless of oxygen availability, targeting …


Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar Jan 2023

Dna Damage Response Activates The Electron Transport Chain And Oxidative Metabolism By Two Parallel Mechanisms, Shreya Nagar

Theses and Dissertations

The DNA damage response (DDR) is an evolutionarily conserved process essential for cell survival. Major part of DDR is coordinated by DNA damage checkpoint (DDC). In addition to DDC, eukaryotic cells also have DNA replication checkpoint (DRC) that is distinct from the DDC and specifically signals slowly progressing or arrested replication forks. DDR involves stalling or arrest of the cell cycle, initiation of DNA repair, and altered regulation of transcription, translation, and the ubiquitin-proteasome system. DDR also triggers transcription shut-off of histone genes. One of the key outcomes of DDC/DRC activation is the increased synthesis of the deoxyribonucleoside triphosphates (dNTPs), …


Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar Jan 2023

Mancozeb Exposure Results In Oxidative Stress And Disruption Of Mitochondrial Complexes Iii & Iv In Transformed Human Colon Cells, Amanda Dhaneshwar

Theses and Dissertations

The ethylene bisdithiocarbamate pesticides, a subclass of the dithiocarbamate pesticides, are broad spectrum organometallic fungicides used on a variety of crops. The fungicide Mancozeb is comprised of an ethylene bisdithiocarbamate backbone complexed to the metals manganese and zinc. Ingestion of food containing pesticide residue and occupational exposure are common routes of Mancozeb exposure. Previous work demonstrated that Mancozeb exposure to HT-29 colon cancer cells resulted in cytotoxicity, apoptosis, and disruption of mitochondrial complex I, II, and V activity. The current study investigated the effect of Mancozeb exposure on mitochondrial complex III and IV activity and oxidative stress parameters in the …


Interferon Gamma Signaling In Ovarian Cancer Cells, Bijaya Gaire Jan 2023

Interferon Gamma Signaling In Ovarian Cancer Cells, Bijaya Gaire

Theses and Dissertations

Interferon gamma (IFNγ) is a pleiotropic cytokine that can have, depending on the cellular and molecular context, both anti-tumor and pro-tumorigenic functions. IFNγ expression can be induced in cancer cells in response to radiation therapy or immune checkpoint blockade used in cancer treatment. We have previously shown that IFNγ induces expression of the Bcl3 proto-oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation and migration, but the mechanisms are unknown. Here, I demonstrate that the IFNγ-induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFkB. Furthermore, my data show that the IFNγ-induced Bcl3 expression …


Gating And Pathogenic Mechanism Of Polycystin Ion Channels, Yan Wang Jan 2023

Gating And Pathogenic Mechanism Of Polycystin Ion Channels, Yan Wang

Theses and Dissertations

Autosomal dominant polycystic kidney disease (ADPKD), one of the most common and life-threatening human genetic diseases, is caused by mutations in PKD1 or PKD2 genes. PKD1 gene encodes PKD1 (also known as polycystin-1 or PC1) protein, which are the founding members of the PKD1 proteins family; while PKD2 encodes TRPP2 (also known as polycystin-2 or PC2) protein, the founding member of the TRPP subfamily. PKD1 family consists of PKD1, PKD1L1, PKD1L2, PKD1L3, and PKDREJ. Whereas the TRPP subfamily includes: TRPP2, TRPP3, and TRPP5. Proteins in PKD1 and TRPP families are collectively called polycystins. TRPP proteins can either form homotetrameric ion …


Genetically Encoded Iron Sensor Cell Line: A Model For Studying Ferroptosis And Cellular Iron Metabolism, Daoud F. Rahman Jan 2023

Genetically Encoded Iron Sensor Cell Line: A Model For Studying Ferroptosis And Cellular Iron Metabolism, Daoud F. Rahman

Theses and Dissertations

Cell death is a biological process that is essential in proper cellular homeostasis, development, and function. Malfunction of this system can lead to different diseases and cancers. Ferroptosis is a form of cell death that occurs as a result of the accumulation of lipid peroxides, that are dependent on intracellular levels of iron. Iron is essential to multiple metabolic processes in the cell, including the catalyzation of lipid peroxides. Thus, intracellular iron levels must be tightly regulated. Our goal is to create a cellular model to study and detect changes in intracellular iron levels. Through the use of a genetically …


Insight Into Eleutherodactylus Coqui Resilience And Anuran Hypoxia Tolerance Utilizing Pincho, Randy Ortiz Jan 2023

Insight Into Eleutherodactylus Coqui Resilience And Anuran Hypoxia Tolerance Utilizing Pincho, Randy Ortiz

Theses and Dissertations

The onset of high-throughput RNA-sequencing (RNA-seq) technology allowed research into transcriptomics to accelerate exponentially aided by the rapid advancement of bioinformatic pipelines. The Pincho workflow, my first research endeavor, is a transcriptomic workflow developed to create an avenue of high-quality reconstructions from RNA-seq data. High-quality reconstruction standards entail longer transcripts, more complete transcripts, and more raw data utilization. We have discovered an ideal trio of assemblers between transABySS, rnaSPAdes and TransLiG that would best reconstruct next-generation sequencing data according to these standards. We utilized Pincho to drive two distinct experiments: (1) exploring the genetic basis for the successful invasion of …


Development Of Whole-Cell Biosensors For Early Detection Of Oral Squamous Cell Carcinoma, Sharona Adina Priyev Jan 2023

Development Of Whole-Cell Biosensors For Early Detection Of Oral Squamous Cell Carcinoma, Sharona Adina Priyev

Theses and Dissertations

Accurate and timely diagnosis is crucial in preventing progression to advanced disease stages and in improving survival rates of oral squamous cell carcinoma (OSCC). Using synthetic biology tools, we aim to integrate synthetic biological circuits into the construction of a novel, whole-cell biosensor (WCB) that will detect salivary biomarkers of OSCC. In treating biological parts and genetic circuits as modular pieces, we can intentionally rearrange selected domains of interest to create new transcription factors that will enable the detection of molecules of interest. Our end-goal is the creation of portable devices carrying living cells that express our synthetic genetic circuits …


Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee Jan 2023

Cytotoxicity Of Copper (Ii) Octanoate On Mouse Hippocampal Astrocytes, Ali A. Shohatee

Theses and Dissertations

Copper, as an essential trace element, is crucial for various biological processes but has also been utilized as a constituent of various pesticides for decades. Copper (II) octanoate is a pesticide utilized as a fungicide and is approved for use in the production of certified organic foods. Previous studies have implicated copper as an inducer of oxidative stress and activator of the Nrf2-ARE pathway. Nrf2 is essential in regulating the transcription of various genes to alleviate toxicity such as those involved in glutathione synthesis and detoxification. Due to the limited toxicological data, this study into the potential induction of oxidative …


Overexpression Of Abcc1 And Abcg2 Confers Resistance To Bmn-673, A Poly (Adp-Ribose) Polymerase (Parp) Inhibitors, Qiuxu Teng Jan 2023

Overexpression Of Abcc1 And Abcg2 Confers Resistance To Bmn-673, A Poly (Adp-Ribose) Polymerase (Parp) Inhibitors, Qiuxu Teng

Theses and Dissertations

Cancer remains a growing public health challenge worldwide. Although the development of chemotherapies has effectively reduced the cancer death rate and improved patients’ prognosis, the frequent occurrence of multi-drug resistance (MDR) in cancer has caused impairments on the efficacy of many structure-unrelated anticancer agents, leading to treatment failure and recurrence. One of the most common causes of MDR is the overexpression of ATP-binding cassette (ABC) transporters on cancer cell membranes, which transport anticancer drugs out of cancer cells, thereby reducing the intracellular drug concentration. BMN-673 (talazoparib) is a potent poly (ADP-ribose) polymerase (PARP) inhibitor that is approved for BRCA-mutated HER2-negative …


Design Of A Synthetic Temperature-Activated Epigenetic Biocontainment System, Owen Rivers Page Jan 2022

Design Of A Synthetic Temperature-Activated Epigenetic Biocontainment System, Owen Rivers Page

Theses and Dissertations

The need for an internal control to govern engineered strain survival is becoming apparent when considering the biosafety and ethics within biotechnological research. Using understudied regulatory elements known as RNA thermometers (RNATs) that can modulate protein translation based on temperature changes and a Type II restriction modification system, we posit the creation of a synthetic temperature-activated epigenetic biocontainment system, termed the ‘sentinel switch’. We have mined a wide variety of bacteria from Yersinia pestis to Synechocystis sp. looking for novel RNATs. A complementary synthetic biology approach based on library generation and screening of chimeric RNATs (ChRNATs) was also conducted. RNATs …


Identification Of Novel Phosphorylation Sites In Sars-Cov-2 Nucleocapsid Protein, Josie Daldegan Rezende Jan 2022

Identification Of Novel Phosphorylation Sites In Sars-Cov-2 Nucleocapsid Protein, Josie Daldegan Rezende

Theses and Dissertations

COVID-19, the 2019 disease outbreak, continues to cause severe mortality worldwide. Fast and reliable tests that identify the SARS-CoV-2 virus, which is responsible for causing the COVID-19 disease, are crucial for controlling the spread of the virus. Antigen tests are ideal for the rapid diagnosis of COVID-19. Current antigen tests for COVID-19 detect the SARS-CoV-2 nucleocapsid (N) protein. The nucleocapsid is the most abundant protein produced by the virus upon infection, which makes it a superior target for detection by an antigen test. Nucleocapsid proteins from several coronaviruses, including SARS, have previously been shown to be modified by posttranslational modification …


Regulation Of Interferon- Induced Interleukin-8 And Pd-L1 Expression In Ovarian Cancer Cells, Sveta Padmanabhan Jan 2022

Regulation Of Interferon- Induced Interleukin-8 And Pd-L1 Expression In Ovarian Cancer Cells, Sveta Padmanabhan

Theses and Dissertations

Interferon-γ (IFNγ) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFNγ has been used in cancer treatment. However, IFNγ also has tumor-promoting functions that are less well understood. Here, I show that IFNγ induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFNγ-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NFκB, and is associated with an increased occupancy of K314/ 315 acetylated p65 NFκB and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody …


Functional Modulation Of The Cav3.1 Calcium Channel By Alternative Splicing At The C-Terminus, Ruizhi Wang Jan 2022

Functional Modulation Of The Cav3.1 Calcium Channel By Alternative Splicing At The C-Terminus, Ruizhi Wang

Theses and Dissertations

The CACNA1G gene encodes for Cav3.1, the alpha-1G subunit of a low-voltage-activated T-type calcium channel, which plays crucial roles in cardiac and smooth muscle cells and neurons by influencing the transmembrane potentials and regulating intracellular Ca2+ signaling. Heterozygous missense mutations in the CACNA1G gene cause spinocerebellar ataxia-42 (SCA42), a heterogeneous group of neurodegenerative disorders characterized by brainstem and cerebellum degeneration, and mice that are null for this gene present severe motor coordination defects, abnormal electrical conductance in the heart, aberrant action potentials in the brain, disrupted sleeping patterns, and absence epilepsy. Different splice variants of Cav3.1 have been described, and …


Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson Jan 2022

Dithiocarbamates Mancozeb And Disulfiram Induce Striated Muscle Myopathy And Neuropathy In Long-Evans Rats, Olivia Stephenson

Theses and Dissertations

Mancozeb (MZ), an ethylene bis-dithiocarbamate complexed with the metals manganese and zinc, is a broad-spectrum fungicide used primarily on orchards and vineyards. Disulfiram (DS, Antabuse®), a diethyldithiocarbamate, is an FDA-approved drug used for alcohol aversion therapy. Both dithiocarbamates (DTCs) have shown neurological effects including motor impairment, muscle weakness, and hind-limb paralysis, although the mechanism of toxicity is not understood. The purpose of this study is to determine how these neurotoxic compounds are damaging striated muscle of rats. Adult, male Long-Evans rats were administered either 250mg/kg MZ or 750mg/kg DS via oral gavage 3x/week for four weeks. Animals were euthanized 24 …


N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei Jan 2022

N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …


Human Otop1 Proton Channel Can Function As A Monomer, Gabriella Abigail Ulloa Jan 2022

Human Otop1 Proton Channel Can Function As A Monomer, Gabriella Abigail Ulloa

Theses and Dissertations

Otopetrins (OTOP) represent a new family of eukaryotic proton channels that do not share structural similarities with other renowned ion channels. Otop1 was initially known for its involvement in vestibular function and its significance for otoconia formation before it was established as a bona fide sour taste receptor. The cryo-EM structures for several Otop channels have been determined and demonstrated Otop1 as a homodimer comprised of two subunits. Each subunit constitutes twelve transmembrane helices that can be further partitioned into two structurally similar six transmembrane domains designated as the N and C domains. Molecular dynamic simulations have also previously shown …


Evolution And Flower Shape From The Hawaiian Lobelioids To The Campanulaceae, Jingjing Tong Jan 2021

Evolution And Flower Shape From The Hawaiian Lobelioids To The Campanulaceae, Jingjing Tong

Theses and Dissertations

Campanulaceae, with roughly 2,400 species, is divided into five subfamilies, in part, by differences in their floral orientation and symmetry, with broad transitions between radial and bilateral floral symmetry. The Hawaiian lobelioids in the Campanulaceae is the largest endemic clade of Hawaiian angiosperms, and they have long been viewed as one of the most spectacular examples of an adaptive radiation in plants. In the first part of our study, we focus on Clermontia, which is one of the largest genera of Hawaiian lobelioids, employing variable low-copy nuclear gene sequences to determine their phylogenetic relationships. We use intron regions from four …


Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen Jan 2021

Alpha-Synuclein Multimerization Is Dependent On Structural Characteristics Of Repeated Ktkegv Regions, Benjamin Ira Rosen

Theses and Dissertations

Parkinson’s disease (PD) is the most common movement disorder and is characterized by neuronal loss and the presence of Lewy bodies in dopaminergic neurons of the substantia nigra pars compacta. PD is a chronic, progressive, and irreversible neurodegenerative disorder associated with the selective loss of dopaminergic neurons. Initially described in an Ayurvedic medical treatise and Galen’s writings, and later by James Parkinson in 1817, the most common symptoms of PD are resting tremors, abnormal posture and gait, and muscle rigidity. Approximately 1 million people are living with PD in the United States and worldwide estimates are between 7 and 10 …


Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi Jan 2021

Microrna Regulation And Cellular Proteostasis In Parkinson's Disease, Alberim Kurtishi

Theses and Dissertations

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder predominately affecting the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease (AD) affecting over 1 million individuals in the US alone. Recent studies have tried to understand the exact nature in which healthy neurons transition to a degenerative state in PD. There are a multitude of combinatory factors that can lead to the development of PD including environmental factors, genetic factors, and aging. The majority of PD cases are sporadic in nature, however familial cases account for 5-10% of total PD cases world-wide. The hallmark …


The Ion Channel Trpm7 Regulates Zinc Depletion-Induced Mdmx Degradation, Herui Wang Jan 2021

The Ion Channel Trpm7 Regulates Zinc Depletion-Induced Mdmx Degradation, Herui Wang

Theses and Dissertations

Zinc deficiency has been linked to human diseases including cancer. p53, a zinc-containing transcription factor, is the most frequently mutated tumor suppressor protein in human cancer. MDM2 and MDMX are zinc- containing proteins and crucial negative regulators of p53, which have been found to be amplified or overexpressed in various cancers. To investigate the effects of zinc depletion on the p53 signaling pathway, we have used ion chelators TPEN and bispicen as well as zinc-deficient medium to treat cells. We report here that zinc depletion results in MDMX degradation in a ubiquitination-independent and 20S proteasome-dependent manner. Restoration of zinc recovers …


Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain Jan 2021

Rna Splicing In Neuron Physiology And Neurodegenerative Diseases, Md Faruk Hossain

Theses and Dissertations

Gene expression is regulated at multiple levels, including transcription, RNA editing, pre-mRNA splicing, mRNA export, translation, and posttranslational modifications. Alternative splicing is a process by which exons can be included or excluded, giving rise to multiple mRNA isoforms from the same transcript. Alternative splicing is an important mechanism in developmental, tissue- and cell-specific control of gene expression, and it is key for expanding proteomic diversity and complexity from a limited number of genes. Moreover, more than 95% of multiexon genes undergo alternative splicing in humans, and about half of all disease-causing point mutations in humans affect pre-mRNA splicing, including neurological …


Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez Jan 2021

Characterizing Ferroptosis Pathways In In Vitro Motor Neuron Models, Alejandra Martinez

Theses and Dissertations

Ferroptosis is a non-apoptotic regulated form of cell death driven by the toxic accumulation of lipid peroxides and the presence of iron. The mechanism by which ferroptosis operates requires further investigation; here I will discuss the findings regarding the role of ferroptosis in different cellular models as well as the genes that may be involved with either promoting or hindering the ferroptotic pathway. NSC-34 is a hybrid cell line of neuroblastoma and primary spinal cord cells that can be differentiated into a motor neuron-like state allowing the characterization of ferroptosis in two distinct cellular conditions. Additionally, iNIL cells are a …