Medicine and Health Sciences Commons^™

9-Phenanthrol And Flufenamic Acid Inhibit Calcium Oscillations In Hl-1 Mouse Cardiomyocytes, Rees A. Burt

Undergraduate Honors Theses

Electrical potentials exist across the membranes of nearly every cell type in the body. In addition, excitable cells, such as neurons, myocytes and even some endocrine cells elicit electrochemical fluctuations, action potentials (AP), in the cell membrane to initiate cell-to-cell communication or intracellular processes. The basis for the electrical potential is rooted within an array of complex interactions between monovalent ions and their associated membrane channels and transporters that regulate the flux of these charged species across the hydrophobic bilayer. Here, an expansion of our recently published work [1] will serve to explore the modern concepts regarding the …

Lrh1 As A Driving Factor For Cancer Development, Alissa M. Margraf

Senior Honors Projects

LRH1 as a driving factor for cancer development

Alissa Margraf, Qi Tang, Qiushi Lin, Xiaoqun Dong

Department of Biomedical and Pharmaceutical Science, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881 USA

Cancer is a major public health problem worldwide. Colon cancer ranks as the third most common causes of cancer mortality in the United States, with an estimated 96,830 new cases and 50,310 deaths in 2014. Colon cancer develops in the digestive tract where benign growths called polyps transform into malignant tumors. Colon cancer cells invade and destroy nearby tissue and can …

Congenital Pituitary Stalk Deformity, Maura Bucciarelli Do, Gretchen Perilli Md

Department of Medicine

No abstract provided.

Cushing’S Storm Secondary To Ectopic Acth Secreting Metastatic Breast Cancer, Maura Bucciarelli Do, Ya-Yu Lee Md, Vasudev G. Magaji Md, Ms

Department of Medicine

No abstract provided.

The Role Of Glutamate Signalling In Diabetic Neuropathy, Nadia Hussain

Dissertations

The majority of diabetics develop neuropathy, which can be debilitating, but the underlying pathophysiological mechanisms are poorly understood. Diabetic neuropathy progresses in a distal to proximal manner. Previous studies have shown that glutamate, the most common excitatory neurotransmitter, plays a role in the pathogenesis of neuropathy. The reason why the role of glutamate in nociception becomes a problem in diabetes and the mechanisms that are involved are unknown. Based on the preliminary data, the hypothesis was that glutamate pathways are likely to be involved in diabetic neuropathy particularly neuropathic pain. Pathways were investigated to look for changes that might reflect …

Hypoxic Signals In The Ischemic Myocardium: Role Of Galectin-1 And Galectin-3, Satwat Hashmi

Dissertations

Myocardial infarction is the most serious manifestation of coronary artery disease and the cause of significant levels of mortality and morbidity worldwide. Galectin-1 (GAL-1) and Galectin-3 (GAL-3) are beta galactoside binding lectins with diverse functions. Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor mediating early and late responses to myocardial ischemia. We aim to study the direct effects of ischemia on GAL-1, GAL-3 and HIF-1α in the heart. Male C57B6/J and GAL-3 knockout mice were used for our two disease models. In the Myocardial infarction (MI) model, the left anterior descending artery of the heart is permanently ligated to …

Role Of Membrane Fusion Protein Ykt6 In Regulating Epithelial Cell-Cell And Cell-Matrix Adhesions., Supriya Joshi

Theses and Dissertations

Intercellular junctions and cell-matrix adhesions play important roles in the maintenance of epithelial integrity. Assembly and remodeling of the plasma membrane complexes are regulated by membrane trafficking and fusion. This thesis is aimed to elucidate the roles of an important membrane fusion protein, Ykt6, in the regulation of epithelial cell adhesion and migration. For the first time, we show that Ykt6 is essential for assembly of adherens junctions and tight junctions in human prostate epithelial cells. We also observed that Ykt6 negatively regulates both collective epithelial cell migration and cell invasion into Matrigel. The effects of YKT6 on epithelial junctions …

The Role Of Cytoprotective And Non-Protective Autophagy In Radiation Sensitivity In Breast Tumor Cells, Jade Le

Theses and Dissertations

In general, ionizing radiation promotes cytoprotective autophagy in a majority of breast tumor cells. Previous studies from our laboratory indicated that radiation (5x2 Gy) induces cytoprotective autophagy in MCF-7 cells. In the current work, inhibition of autophagy by silencing of Beclin-1 in MCF-7 cells resulted in an increase in sensitivity to radiation based both on cell number and clonogenic survival; however, there was no increase in apoptosis and the basis for this sensitization is currently under investigation. Unexpectedly, enhancement of autophagy by silencing of Bcl-2 also led to an increase in sensitivity to radiation, possibly through the conversion of cytoprotective …

Adenosine Production Is Essential For Closing The Critical Period Of Cortical Plasticity, Rachel A. Chassan

Theses and Dissertations (ETD)

Sensory inputs from the external world are represented as highly organized systems in the adult brain for effective adaptation to the environment. At the cortical level, this organization is referred to as cortical maps. The establishment of cortical maps begins with early life experiences during the critical period, a brief period during development of heightened sensitivity to sensory stimuli. During this time, organization of cortical maps is plastic and highly subject to change through passive sensory experience. As an animal matures, the critical period closes and changes to cortical maps occur less freely. The cellular mechanisms of cortical map plasticity …

Predicting Targeted Drug Combinations Based On Pareto Optimal Patterns Of Coexpression Network Connectivity, Nadia M. Penrod, Casey S. Greene, Jason H. Moore

Dartmouth Scholarship

Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced …

Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot De Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.

Results. Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared …

Tumor Microenvironment-Based Feed-Forward Regulation Of Nos2 In Breast Cancer Progression, Julie L. Heinecke, Lisa A. Ridnour, Robert Y.S. Cheng, Christopher H. Switzer, Michael M. Lizardo, Chand Khanna, Sharon A. Glynn, S. Perwez Hussain, Howard A. Young, Stefan Ambs, David A. Wink

United States Public Health Resources

Inflammation is widely recognized as an inducer of cancer progression. The inflammation-associated enzyme, inducible nitric oxide synthase (NOS2), has emerged as a candidate oncogene in estrogen receptor (ER)-negative breast cancer, and its increased expression is associated with disease aggressiveness and poor survival. Although these observations implicate NOS2 as an attractive therapeutic target, the mechanisms of both NOS2 induction in tumors and nitric oxide (NO)-driven cancer progression are not fully understood. To enhance ourmechanistic understanding of NOS2 induction in tumors and its role in tumor biology, we used stimulants of NOS2 expression in ER- and ER+ breast cancer cells and examined …

A Potentially Fatal Etiology Of A Lumbar Radiculopathy, Katie Mastoris Do, Ranjit R. Nair Md, E York Md

Department of Medicine

No abstract provided.

Inborn Error Of Metabolism Is A Disease Of Any Age; Carniting Palmitoyltransferase Ii Deficiency And Its Manifestations, Mira Mitry Md, James Ross Md, Facp

Department of Medicine

No abstract provided.

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

The Roles Of Krüppel-Like Transcription Factors Klf1 And Klf2 In Mouse Embryonic And Human Fetal Erythropoiesis, Divya Vinjamur

Theses and Dissertations

Hemoglobinopathies are some of the most common monogenic disorders in the world, affecting millions of people and representing a growing burden on health systems worldwide. Although the pathophysiology of sickle cell anemia and beta-thalassemia, two of the most common hemoglobinopathies, have been the focus of much research over the last century, patients affected by these diseases still lack a widely applicable and easily available cure. Sickle cell anemia and beta-thalassemia are caused by defects in the structure and production of the beta-globin chains that, along with the alpha-globin chains make up the heterotetrameric hemoglobin molecule. Studies geared towards re-expression of …

The Microbiome In Pediatric Cystic Fibrosis Patients: The Role Of Shared Environment Suggests A Window Of Intervention, Thomas H. Hampton, Deanna M. Green, Garry R. Cutting, Hilary G. Morrison, Mitchell L. Sogin, Alex H. Gifford, Bruce A. Stanton, George A. O’Toole

Dartmouth Scholarship

Cystic fibrosis (CF) is caused by mutations in the CFTR gene that predispose the airway to infection. Chronic infection by pathogens such as Pseudomonas aeruginosa leads to inflammation that gradually degrades lung function, resulting in morbidity and early mortality. In a previous study of CF monozygotic twins, we demonstrate that genetic modifiers significantly affect the establishment of persistent P. aeruginosa colonization in CF. Recognizing that bacteria other than P. aeruginosa contribute to the CF microbiome and associated pathology, we used deep sequencing of sputum from pediatric monozygotic twins and nontwin siblings with CF to characterize pediatric bacterial communities and the …

Cytoprotective Versus Non-Protective Autophagy Induced By Radiation In Head And Neck Cancer Cells, Duaa Bakhshwin

Theses and Dissertations

The primary treatment options for head and neck cancer are radiation therapy or surgery, or both combined; chemotherapy is often used as an additional, or adjuvant, treatment. Patients treated with radiotherapy are exposed to a high cumulative dose of radiation over a period of time and there is a 17-33% chance of recurrence. High cumulative doses of radiation, a long time course of treatment, side effects and the possibility of recurrence provide the rationale for developing approaches for radiation sensitization, which could be helpful to patients in decreasing the dose, duration of radiation, side effects, or the chance of recurrence. …

The Relationship Of Body Mass Index On Primary Care Physician Practice Behaviors With Their Overweight And Obese Patients, Kevin A. Vrablik Md, Mph, Facoem, Judith Green-Mckenzie Md, Mph, Facoem, Steven W. Godin Phd, Mph, Phi Certificate

Department of Medicine

No abstract provided.

Hydration Status And Performance During Two-A-Day Summer Soccer Training Sessions With Female Athletes, Kristina Burk

Celebrating Scholarship & Creativity Day (2011-2017)

No abstract provided.

Limited Brain Metabolism Changes Differentiate Between The Progression And Clearance Of Rabies Virus., Keith Schutsky, Carla Portocarrero, D Craig Hooper, Bernhard Dietzschold, Milosz Faber

Department of Microbiology and Immunology Faculty Papers

Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of …

Serum 25-Hydroxyvitamin D Status And Anaerobic Performance In Female Collegiate Basketball Players, Anna Krieger

Celebrating Scholarship & Creativity Day (2011-2017)

This presentation examines the relationship between vitamin D status and anaerobic performance; determines if the temporary deficiency that occurs during the late fall and winter months is associated with decreased anaerobic performance; and examines the efficacy of 2000 IU vitamin D₃ daily supplementation to maintain and/or improve vitamin D status in female young adults.

Characterization Of Extraction Methods To Recover Phenolic Rich Extracts From Pinto Beans That Exert High Antioxidative Activities Using Response Surface Approach, Mohammed Aldawsari

Department of Food Science and Technology: Dissertations, Theses, and Student Research

The pinto bean has been linked to the prevention of multiple diseases due in large part to the presence of phenolic antioxidants, which are higher in beans than in many fruits and vegetables. These components deliver health properties beyond basic nutritional characteristics by scavenging free oxygen radicals. However, these benefits are most likely due to the ability of these chemically diverse phenols to impart greater protective properties as additives or synergists acting in combination. However, optimal parameters to isolate these compounds (in terms of ratios and types) from a given natural source are not known. Without this knowledge, understanding the …

Comparing Dietary Patterns Of College Students When Eating In America Versus Eating In China: Impact On Nutrition Intake, Body Weight And Waist Circumference, Maoxinyu (Daisy) Wu

Celebrating Scholarship & Creativity Day (2011-2017)

No abstract provided.

Irradiation Of Hs578t Breast Tumor Cells Induces Non-Cytoprotective Autophagy, Aisha Alhaddad

Theses and Dissertations

Cancer is the second most common cause of death in the US. The most frequently observed cancer type in women is breast cancer. A special type of breast cancer is triple negative (TNBC) cancer that is characterized by lacking three receptors: estrogen, progesterone and human epithelial growth factor (HER 2). The HS578t breast cell line is a model of TNBC that also has a mutation of the p53 protein. Ionizing radiation is used widely in the clinic to debulk tumors before surgery as well as post-surgery to eliminate residual tumor cells outside the surgical field. Previous studies from our laboratory …

Role Of Anillin In Regulation Of Epithelial Junctions, Gibran Chadha

Theses and Dissertations

Adherens junctions (AJs) and tight junctions (TJs) are characteristic features of differentiated epithelial cells and are critical for regulation of epithelial barriers and cell polarity. Integrity and remodeling of epithelial junctions depend on their interactions with underlying actomyosin cytoskeleton. Anillin is a multifunctional scaffold able to interact with different cytoskeletal proteins including F-actin and Myosin II. This project aimed to investigate roles of anillin in regulating epithelial AJs and TJs. Using A549 human lung epithelial and DU145 human prostate epithelial cells, we demonstrated the anillin depletion-induced loss of AJs and TJs. This was accompanied by disorganization of perijunctional actomyosin belt …

Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart

Dartmouth Scholarship

Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy …

The Effect Of Size On Ag Nanosphere Toxicity In Macrophage Cell Models And Lung Epithelial Cell Lines Is Dependent On Particle Dissolution, Raymond F. Hamilton, Sarah Buckingham, Andrij Holian

Biomedical and Pharmaceutical Sciences Faculty Publications

Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage and epithelial cell lines. The results indicated that smaller Ag (20 nm), regardless of coating, were more toxic in both cell types and most active in the THP-1 macrophages. TEM imaging demonstrated that 20 nm Ag nanospheres dissolved more rapidly than 110 nm Ag nanospheres in acidic phagolysosomes consistent with Ag ion mediated toxicity. In addition, there …

A Comparison Of Clustering And Missing Data Methods For Health Sciences, Ran Zhao, Deanna Needell, Christopher Johansen, Jerry L. Grenard

CMC Faculty Publications and Research

In this paper, we compare and analyze clustering methods with missing data in health behavior research. In particular, we propose and analyze the use of compressive sensing's matrix completion along with spectral clustering to cluster health related data. The empirical tests and real data results show that these methods can outperform standard methods like LPA and FIML, in terms of lower misclassification rates in clustering and better matrix completion performance in missing data problems. According to our examination, a possible explanation of these improvements is that spectral clustering takes advantage of high data dimension and compressive sensing methods utilize the …

Eculizumab In The Successful Treatment Of Postpartum Hemolytic Uremic Syndrome - A Case Report, Craig A. Mackaness Do, Frederick S. Fleszler Md

Department of Medicine

No abstract provided.