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Articles 1 - 30 of 58
Full-Text Articles in Molecular Biology
Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill
Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill
SURE Journal: Science Undergraduate Research Experience Journal
Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Functional Analysis Of Recurrent Non-Coding Variants In Human Melanoma, Paula Maria Godoy
Arts & Sciences Electronic Theses and Dissertations
Worldwide incidence rates of cutaneous melanoma are increasing, and while survival rates for early stages of melanoma are high, rates drop precipitously for metastatic melanomas or those that are unable to be targeted by currently available treatments. As melanomas have a propensity to quickly metastasize, understanding the contributions of melanoma initiation remains critical for early intervention. Onset of melanoma is characterized most by mutations that stimulate mitogen-activated protein kinase (MAPK) signaling, disrupt DNA damage checkpoints, and trigger mechanisms to bypass senescence through elongation of telomeres. Additionally, in zebrafish melanoma models, the earliest cluster of melanoma-initiating cells activate expression of a …
Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae, Kyle Andrew Hubble
Dpc29 Promotes Mitochondrial Translation Post-Initation In Saccharomyces Cerevisiae, Kyle Andrew Hubble
Graduate School of Biomedical Sciences Theses and Dissertations
Although the cytosolic and bacterial translation systems are well studied, much less is known about translation in mitochondria. In the yeast Saccharomyces cerevisiae, mitochondrial gene expression is predominately regulated by translational activators. These regulators are thought to promote translation by binding the elongated 5’-UTRs on their target mRNAs. Since mammalian mitochondrial mRNAs generally lack 5’-UTRs, they must regulate translation by other mechanisms. As expected, most yeast translational activators lack orthologues in mammals. Recently, a mitochondrial gene-specific translational activator, TACO1, was reported in mice and humans. To better define its role in mitochondrial translation I examined the yeast TACO1 orthologue, DPC29. …
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam
Ankyrin Dependent Mitochondrial Function And Bioenergetics In The Heart, Janani Subramaniam, Janani Subramaniam
Dissertations & Theses (Open Access)
ANK2 mutations in patients are associated with numerous arrhythmias, cardiomyopathies, and other heart defects. In the heart, AnkB, the protein encoded by ANK2, clusters relevant ion channels and cell adhesion molecules in several important domains; however, its role at Mitochondria Associated ER/SR Membranes (MAMs) has yet to be investigated. MAMs are crucial to mitochondrial function and metabolism and are signaling hubs implicated in various cardiac pathologies. Among several functions, these sites mediate the direct transfer of calcium from the ER/SR to the mitochondria to modulate ATP synthesis. Given that mitochondrial function and energy production are paramount to cardiovascular heath, …
T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones
T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones
Biomedical Sciences Theses & Dissertations
Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …
Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean
Gating Intermediates Reveal Inhibitory Role Of The Voltage Sensor In A Cyclic Nucleotide-Modulated Ion Channel, Xiaolong Gao, Philipp A M Schmidpeter, Vladimir Berka, Ryan J Durham, Chen Fan, Vasanthi Jayaraman, Crina M Nimigean
Journal Articles
Understanding how ion channels gate is important for elucidating their physiological roles and targeting them in pathophysiological states. Here, we used SthK, a cyclic nucleotide-modulated channel from Spirochaeta thermophila, to define a ligand-gating trajectory that includes multiple on-pathway intermediates. cAMP is a poor partial agonist for SthK and depolarization increases SthK activity. Tuning the energy landscape by gain-of-function mutations in the voltage sensor domain (VSD) allowed us to capture multiple intermediates along the ligand-activation pathway, highlighting the allosteric linkage between VSD, cyclic nucleotide-binding (CNBD) and pore domains. Small, lateral displacements of the VSD S4 segment were necessary to open the …
The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahi, Md Amran Gazi, Ali Faisal Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere
The Childhood Acute Illness And Nutrition (Chain) Network Nested Case-Cohort Study Protocol: A Multi-Omics Approach To Understanding Mortality Among Children In Sub-Saharan Africa And South Asia, James M. Njunge, Kirkby Tickell, Abdoulaye Hama Diallo, Abu Sadat Mohammad Sayeem Bin Shahi, Md Amran Gazi, Ali Faisal Saleem, Zaubina Kazi, Syed Ali, Caroline Tigoi, Ezekiel Mupere
Department of Paediatrics and Child Health
Introduction: Many acutely ill children in low- and middle-income settings have a high risk of mortality both during and after hospitalisation despite guideline-based care. Understanding the biological mechanisms underpinning mortality may suggest optimal pathways to target for interventions to further reduce mortality. The Childhood Acute Illness and Nutrition (CHAIN) Network ( www.chainnnetwork.org) Nested Case-Cohort Study (CNCC) aims to investigate biological mechanisms leading to inpatient and post-discharge mortality through an integrated multi-omic approach.
Methods and analysis; The CNCC comprises a subset of participants from the CHAIN cohort (1278/3101 hospitalised participants, including 350 children who died and 658 survivors, and …
Occurrence Of Kanamycin-Resistant Bacteria Relative To Anthropogenic Pollution Along Richland Creek In Nashville, Tn, Jolene Ho Mach, Annie Le, Brandon Torres Ramirez
Occurrence Of Kanamycin-Resistant Bacteria Relative To Anthropogenic Pollution Along Richland Creek In Nashville, Tn, Jolene Ho Mach, Annie Le, Brandon Torres Ramirez
Science University Research Symposium (SURS)
The overuse of antibiotics has caused an increase in antibiotic-resistant (AR) bacteria, which is a serious public health concern. Previous studies showed a significant correlation between anthropogenic pollution and AR bacteria. This project aims to identify AR bacteria in Richland Creek relative to local anthropogenic pollution. Water samples were collected at four locations along Richland Creek in Nashville, Tennessee. Bacteria resistant to the antibiotic kanamycin were isolated from the water samples, identified to genera using DNA barcoding, and compared among the sites. We expect to see a greater abundance and diversity of kanamycin-resistant bacteria closer to the end than near …
Distribution Of Erm Proteins In The Stomach Mucosa Of Normal And Diabetic Rats, Asmaa Salem Al Sereidi
Distribution Of Erm Proteins In The Stomach Mucosa Of Normal And Diabetic Rats, Asmaa Salem Al Sereidi
Theses
Diabetes mellitus (DM), or simply diabetes, refers to a group of metabolic disorders that include a variety of diseases that disrupt our body's metabolism. The long-term uncontrolled disease can lead to stomach complications such as gastroparesis, as well as disruption in several proteins, such as ERM (Ezrin, radixin, moesin) proteins. ERM proteins are three proteins that are structurally and functionally related. ERM proteins have molecular masses of 82, 80, and 75 kDa, respectively. Ezrin is highly expressed in the stomach, especially in parietal cells that secrete gastric acid. ERM proteins function as scaffolding proteins in lipid rafts and granule trafficking …
The Emerging Role Of Notch3 Receptor Signalling In Human Lung Diseases, Manish Bodas, Bharathiraja Subramaniyan, Harry Karmouty-Quintana, Peter F Vitiello, Matthew S Walters
The Emerging Role Of Notch3 Receptor Signalling In Human Lung Diseases, Manish Bodas, Bharathiraja Subramaniyan, Harry Karmouty-Quintana, Peter F Vitiello, Matthew S Walters
Journal Articles
The mammalian respiratory system or lung is a tree-like branching structure, and the main site of gas exchange with the external environment. Structurally, the lung is broadly classified into the proximal (or conducting) airways and the distal alveolar region, where the gas exchange occurs. In parallel with the respiratory tree, the pulmonary vasculature starts with large pulmonary arteries that subdivide rapidly ending in capillaries adjacent to alveolar structures to enable gas exchange. The NOTCH signalling pathway plays an important role in lung development, differentiation and regeneration post-injury. Signalling via the NOTCH pathway is mediated through activation of four NOTCH receptors …
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward
Doctoral Dissertations
Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …
The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong
The Effects Of Prenatal Cannabis Exposure On The Basolateral Amygdala, Karen Kw Wong
Undergraduate Student Research Internships Conference
Clinical and preclinical studies indicate prenatal cannabis exposure (PCE) pathologically affects fetal brain development and may increase vulnerability to neuropsychiatric disorders, including schizophrenia and mood/anxiety disorders. In review research from our lab suggests that fetal exposure to Δ9-THC sex-selectively impairs mesocorticolimbic (MCL) circuit function. However, there is a distinct lack of focus on PCE models on the BLA. The BLA plays a central role within the MCL where it directly interacts with the VTA, PFC and HIPP. Importantly, our model exhibits significant VTA hyperdopaminergic activity, and sex-specific alterations to PFC/HIPP glutamate firing, alongside region- and sex-specific changes in dopamine (DA), …
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Mistranslating Trnas Alter The Heat Shock Activation By Hsf1, Rebecca Dib
Undergraduate Student Research Internships Conference
Translation, or the production of protein from an mRNA blueprint, is among the most fundamental processes to life as we know it. tRNAs are essential to accurate translation, as they decode the codons of mRNA and recruit corresponding amino acids. Variant tRNAs with anticodon mutations can decrease translational fidelity by recruiting the incorrect amino acid, an aberrant process known as mistranslation. When proteins are produced with incorrect amino acid sequences, they may misfold. The heat shock response functions to alleviate cellular stress caused by misfolded proteins, either by refolding or targeting misfolded proteins for degradation. Hsf1 acts as a transcriptional …
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo
Dual Mechanisms Implemented By Lin-28 For Positive Regulation Of Hbl-1 Are Necessary For Proper Development Of Distinct Tissues In Caenorhabditis Elegans, Madeleine Minutillo
Graduate School of Biomedical Sciences Theses and Dissertations
In Caenorhabditis elegans, the heterochronic pathway is comprised of a hierarchy of genes that control the proper timing of developmental events. hbl-1 (Hunchback Like-1) encodes an Ikaros family zinc-finger transcription factor that promotes the L2 stage cell fate events of the hypodermis. The downregulation ofhbl-1 is a crucial step for the transition from the L2 to the L3 stage. There are two known processes through which negative regulation of hbl-1 occurs: suppression of hbl-1 expression by 3 let-7 miRNAs through the hbl-1 3’UTR and inhibition of HBL-1 activity by LIN-46. The mechanisms by which hbl-1 is positively regulated have not …
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia
Dissertations & Theses (Open Access)
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …
Bacterial Chondronecrosis With Osteomyelitis In Broilers: Genomics, Phylogenomics, And Methods To Detect Specific Pathogens During Outbreaks., Abdulkarim Abdulaziz A. Shwani
Bacterial Chondronecrosis With Osteomyelitis In Broilers: Genomics, Phylogenomics, And Methods To Detect Specific Pathogens During Outbreaks., Abdulkarim Abdulaziz A. Shwani
Graduate Theses and Dissertations
Lameness is a major issue in animal welfare and the broiler industry. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main causes of lameness. Many staphylococcal species, including Staphylococcus agnetis isolate 908, have been isolated from the bones and blood of lame broilers at the University of Arkansas. Staphylococcus agnetis is a coagulase-variable, Gram-positive bacterial species that has been previously associated with subclinical or mild clinical cases of mastitis in dairy cattle. The annotated complete genome of hypervirulent strain 908 was published at NCBI. In this study, it has been compared to nine genomes we assembled for hypervirulent isolates …
Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez
Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez
Pharmaceutical Sciences (PhD) Dissertations
Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …
Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn
Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn
Electronic Thesis and Dissertation Repository
To colonize human skin and survive within abscesses, Staphylococcus aureus has evolved mechanisms to evade host innate defenses. USA300 has become the predominate community-acquired methicillin-resistant S. aureus (CA-MRSA) clone, which can be in part attributed to detoxification of unsaturated free fatty acids (uFFA) found in sebum and the nares. Our lab has previously identified the TetR family regulator FarR responsible for induction of the resistance-nodulation-division (RND) superfamily efflux pump FarE to promote efflux of toxic uFFA. However, RND family efflux pumps remain poorly characterized in Gram-positive species and the mechanism by which FarR regulates FarE has yet to be determined. …
A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser
A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser
Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship
Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …
Discovery Of First-In-Class Small Molecule Agonists Of The Rxfp2 Receptor As Therapeutic Candidates For Osteoporosis, Maria Esteban Lopez
Discovery Of First-In-Class Small Molecule Agonists Of The Rxfp2 Receptor As Therapeutic Candidates For Osteoporosis, Maria Esteban Lopez
FIU Electronic Theses and Dissertations
Osteoporosis is a chronic bone disease characterized by decreased bone mass and increased risk of developing fractures, predominantly observed in the elderly. The pathophysiological cause of the disease is a decrease in the activity of the bone-forming cells (osteoblasts) that alters bone remodeling in favor of bone resorption, leading to a decrease in bone mass. Recent studies identified the relaxin family peptide receptor 2 (RXFP2), the G protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), as an attractive target expressed in osteoblast cells to increase bone formation. The goal of this dissertation is to discover and characterize small molecule agonists …
Overexpression Of Foxf2 In Prostate Cancer Cells Causes An Increase In Cancer Cell Apoptosis And A Decrease In Proliferation, Vaughn Poon
Honors Projects
FOXF2 is a transcription factor that plays a crucial role in organ development, and recent studies have shown that it suppresses tumor growth and progression in mouse prostate models by attenuating the cancer-associated fibroblasts (CAF) phenotype and transcriptionally downregulating Cxcl5. However, the effects of FOXF2 overexpression in prostate cancer cells have not been extensively studied. Here, we investigate the impact of FOXF2 overexpression in prostate cancer cells and demonstrate that it leads to a significant increase in cell apoptosis and a decrease in proliferation. These findings suggest that FOXF2 may have potential as an immunotherapy drug target for prostate …
Isolation And Characterization Of Α-Hcd7 Scfv Expressing Exosomes And Synthesis Of Hybrid Exosome-Liposome For Analyses, Sahil Patel
Biotechnology Theses
The goal of this thesis project is to isolate and characterize exosomes that express anti-human CD7 (α-hCD7) single chain variable fragment (scFv), which will be further utilized for T celltargeted gene editing. To reach this goal, exosomes from HEK 293 cells and Jurkat cells were isolated and characterized with different methodologies. To obtain α-hCD7 scFv-expressing exosomes, the HEK 293 cells were subjected to transfection of custom-plasmid pDisplay-αhCD7 scFv, and the expression of α-hCD7 scFv on the HEK 293-derived exosomes were then confirmed by immunogold staining, western blotting, and flow cytometry. To transfect 293 cells, calcium phosphate transfection was utilized, and …
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Defining The Role Of Rare Genetic Variants That Drive Risk And Pathogenesis Of Alzheimer’S Disease, Matthew James Rosene
Arts & Sciences Electronic Theses and Dissertations
Alzheimer’s disease (AD) is the leading cause of dementia and is pathologically defined by the aggregation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Rare heritable mutations within the genes for amyloid precursor protein (APP) and presenilin 1 (PSEN1), and presenilin 2 (PSEN2) cause early onset AD and account for approximately 1% of AD cases. While the majority of AD cases are late-onset (LOAD), which is defined by a markedly more complex genetic architecture that is comprised of many genetic risk factors that influence AD through multiple cellular pathways. The advent of deep sequencing analyses have allowed for the identification …
Eskape Pathogens: The Clinical Prevalence And Molecular Mechanisms Of Antibiotic Resistance, Anusha Attre
Eskape Pathogens: The Clinical Prevalence And Molecular Mechanisms Of Antibiotic Resistance, Anusha Attre
Honors Scholar Theses
The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of all nosocomial, or healthcare-associated (HAI), infections (Navidinia, 2016). The purpose of this research study is to determine the burden of ESKAPE infections on healthcare and study the antibiotic resistance in these high-risk pathogens to provide direction for researchers to develop new antimicrobial innovations to reduce ESKAPE infectivity and improve patient outcomes. To study the burden of ESKAPE infections, this review analyzes the current statistics explaining the clinical prevalence of each pathogen in causing HAIs. Additionally, each pathogen is …
Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer
Lectin-Glycan Complexes: A Comprehensive Analysis Of Docking Calculations, Ashton Custer
Honors Theses
Lectins are a type of glycan-binding protein that noncovalently bind glycans. Carbohydrates are molecules consisting of sugar units joined together. Glycans are carbohydrates. Hence, glycans are also sugars. Lectins and lectin-glycan complexes have a range of biological roles and can be found in animals (including humans), plants, bacteria, viruses, and yeasts and fungi.1 Many scientists focus on the computational study of these complexes due to their intricate roles in many living organisms. Computational study is important in furthering our knowledge of lectin-glycan complexes and other such protein complexes. However, computational study is not perfect. There are many challenges in …
The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman
The Use Of Nebulizer Medications As A Possible Treatment For Covid-19, Jacob Kaufman
Honors College Theses
For the past few years, the COVID-19 pandemic has been the focal point in healthcare and research. This disease has permanently changed daily life and left a historic impact on the world. Most people have felt the effects of this pandemic either directly, via infection, or indirectly, via change in workflow, financial impact, etc. The main question for this virus still remains today; how do we treat this illness effectively? While many ideas are being tested and suggested, a definite answer has yet to be procured. Vaccine rates are climbing on a daily basis, serving as the first and most …
Effect Of Uracil Dna Glycosylase Activity On The Efficacy Of Thymidylate Synthase Inhibitor/Hdac Inhibitor Combination Therapies In Colon Cancer, Rashmi Kulkarni, Brian P Weiser
Effect Of Uracil Dna Glycosylase Activity On The Efficacy Of Thymidylate Synthase Inhibitor/Hdac Inhibitor Combination Therapies In Colon Cancer, Rashmi Kulkarni, Brian P Weiser
Rowan-Virtua Research Day
Human uracil DNA glycosylase (UNG2) is responsible for removing uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5-fluorouracil, fluorodeoxyuridine, and pemetrexed) and we determined that, except for 5-fluorouracil, all other TS inhibitors were significantly more potent in UNG2 KO cells compared to wild-type HT29 cells. Interestingly, UNG2 protein levels …
Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich
Morphine-Induced Hyperactivity Is Attenuated By Intra-Accumbens Administration Of The Highly-Selective Dopamine D3 Receptor Antagonist Vk4-40, Mansi Patel, Desta M. Pulley, Daniel Manvich
Rowan-Virtua Research Day
Opioids exert their abuse-related effects by enhancing dopamine (DA) neurotransmission within the brain’s mesolimbic reward system, a neural projection involving DA neurons in the ventral tegmental area (VTA) that project to medium spiny neurons within the nucleus accumbens (NAc). Mu (MOR) are expressed by several populations of GABAergic neurons that tonically inhibit VTA DA neurons. By inhibiting these GABAergic neurons in a MOR-dependent manner, opioids indirectly enhance DA neurotransmission via disinhibition of DAergic neurons. Accumulating evidence indicates that selective pharmacological antagonism of the dopamine D3 receptor (D3R) attenuates the abuse-related effects of several opioids, but the neurobiological mechanisms mediating this …
Unraveling The Molecular Foundations Behind The Diverged Behaviors Of Mouse Insulin 1 And Insulin 2, Connecting Diabetes Risk With Glucocorticoid Treatment And Chronic Migraine Through The Analysis Of Islet Chemistry, And Capturing Key Posttranslational Modifications All Through The Application Of A Novel Lc-Ims-Ms Workflow, Connor Christopher Long
Select or Award-Winning Individual Scholarship
We display the capabilities of our established liquid chromatography-ion mobility spectrometry-mass spectrometry (LC-IMS-MS) workflow in the investigations of islet chemistry at the sub-single-islet level. We begin by characterizing the structural differences of Ins1 and Ins2 to present novel insights as to why their behaviors diverge. We then examine the effects of the stress hormone corticosterone, the rodent equivalent of human cortisol that is often used as a therapeutic, on pancreatic peptide hormone secretion. We also uncover the molecular connection behind the inverse relationship between type 2 diabetes (T2D) risk and chronic migraine via the neuropeptides CGRP and PACAP. Lastly, we …
Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj
Novel Regulators Of Cellular Secretion Alter The Tumor Microenvironment To Drive Metastasis, Rakhee Bajaj
Dissertations & Theses (Open Access)
Lung cancer is a highly aggressive disease responsible for ~25% of all cancer-related deaths, due in part to its proclivity to metastasize. Treating metastasis holds potential for improving patient survival but requires a deeper investigation into the underlying mechanisms. Some of these processes that can regulate metastasis are: (1) Oncogenic targets of epithelial micro-RNAs (miRNAs) are epigenetically de-repressed upon loss of the miRNAs during epithelial-to-mesenchymal transition (EMT) and in cancer. EMT confers plasticity and fitness to cancer cells promoting their survival through the metastatic cascade. This cascade and EMT are initiated by loss of the miRNA200 family (miR-200) and the …