Digital Commons Network^™

Characterizing The Critical Role Of Metabolic And Redox Homeostasis In Colorectal Cancer, Danielle Frodyma

Theses & Dissertations

Metabolic alterations are a hallmark of cancer and the mechanism by which these adaptations sustain cancer cell growth are complex and dependent on tissue type. In colon cancer, Peroxisome Proliferator Activated Receptor γ Coactivator 1 β(PGC1��) and Estrogen-Related Receptor α (ERR��) are overexpressed and contribute to tumor growth. Previous studies have shown that PGC1�� and ERR�� regulate many metabolic processes by controlling vital gene expression. Here, we show that PGC1�� and ERR�� drive oxidative phosphorylation and glycolysis in colon cancer cell lines and we evaluated downstream effectors and processes.

A dysfunction in the reductive and oxidative capacity of the cell …

Targeted Therapies In Select Gastrointestinal Cancers And Cancer Cachexia, Scott Mulder

Theses & Dissertations

Hepatocellular carcinomas exhibit metabolic alterations to support their proliferative and biosynthetic needs. We identified that elevated expression of the mitochondrial oxidative carboxylase, malic enzyme 2 (ME2), correlates with poorer hepatocellular carcinoma patient survival. Hepatocellular carcinoma patient tumors with high ME2 expression exhibit transcriptomic alterations indicative of PI3K/AKT/mTOR and c-Myc signaling as well as elevated central carbon, fatty acid, and redox metabolism pathways. Depletion of ME2 in the hepatocellular carcinoma cell line PLC or in the livers of mice treated with diethylnitrosamine to chemically induce hepatocellular carcinomas, results in impaired proliferation and reduced tumor formation. Additionally, the loss of …

The Connections Of Music, Culture, And Language: A Qualitative Case Study Of The Musical Experience Of A Newcomer Program, Jessica Strawderman

Masters Theses, 2020-current

In this qualitative case study, I investigated the philosophy and process of an elementary newcomer program and explored the perceived benefits for newcomer students of the musical experience, aiding in transition from full-time English as a second language (ESL) services in self-contained class to a general education setting. The studied school division serves a high population of students who are English Language Learners (ELLs), representing a multitude of languages and cultures. The division places students of immigrant families who have no social or educational experience speaking English in the newcomer program. In order to gain a deep understanding of the …

Pulling Heart Strings: Quality Improvement Algorithm For Temporary Epicardial Pacing Wire Removal Post Cardiac Surgery, Jessica Norman

Doctors of Nursing Practice (DNP) Final Projects, 2020-current

The placement of temporary epicardial pacing wires (TEPW) is considered standard practice post cardiac surgery and is dependent on the patient’s cardiac function intra-operatively and their electrophysiologic profile after weaning from cardiopulmonary bypass (Reade, 2007; Elmistekawy et al, 2016). Complications associated with TEPW removal include myocardial damage, infection, perforation, tamponade, disruption of anastomoses, ventricular arrythmias, and death (Bojar, 2009; Carroll et al, 1998;Timothy & Rodeman, 2004). Currently there is no standard practice on the removal of TEPW and there is wide variation in removal practices involving patients who are routinely on medications such as dual antiplatelet therapies and systemic anticoagulation. …

Bioscience: How One Industry Won The Pandemic And Will Change Us All, Sonya Swink

Capstones

A video and print capstone about the next great generation of biological sciences as a private industry since 2020. It encompasses the pandemic as the boost the industry needed, discussion of science’s bad reputation and the potential benefits, especially for new workspaces and real estate investors. Colorado is a focus as a burgeoning market. The news value of this story as a primer is how this will be both a beneficial industry and one that must be held to account if it becomes too monopolistic. Comparisons are from the viewpoint that bioscience is like the next Silicon Valley, but statements …

Neuroplastin Modulates Anti-Inflammatory Effects Of Manf, Takuya Yagi, Rie Asada, Kohsuke Kanekura, Ave Eesmaa, Maria Lindahl, Mart Saarma, Fumihiko Urano

Open Access Publications

Endoplasmic reticulum (ER) stress is known to induce pro-inflammatory response and ultimately leads to cell death. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER-localized protein whose expression and secretion is induced by ER stress and a crucial survival factor. However, the underlying mechanism of how MANF exerts its cytoprotective activity remains unclear due to the lack of knowledge of its receptor. Here we show that Neuroplastin (NPTN) is such a receptor for MANF. Biochemical analysis shows the physiological interaction between MANF and NPTN on the cell surface. Binding of MANF to NPTN mitigates the inflammatory response and apoptosis via suppression …

Dna Polymerase Ε: Replication Error Prevention And Consequences Of A Cancer-Associated Mutation, Chelsea R. Bulock

Theses & Dissertations

Genome integrity is necessary to prevent mutations and disease. During eukaryotic DNA replication, DNA polymerases ε (Polε) and δ (Polδ) synthesize the leading and lagging strand, respectively. Polε and Polδ also have exonuclease activity that acts in series with post-replicative mismatch repair (MMR) to remove replication errors. Defects in proofreading and MMR lead to an increase in mutations and cause cancer in humans. This dissertation focuses on several unresolved issues involving the relationship between Polε and Polδ in replication error avoidance. First, despite an abundance of data supporting the one-strand-one-polymerase replication fork model, defects in the fidelity of Polε have …

Anti-Muc4Β Antibodies As A Novel Therapeutic Modality For The Treatment Of Pancreatic Cancer, Catherine Orzechowski

Theses & Dissertations

The deregulation of cell surface glycoproteins, such as mucins, is a hallmark of many tumors of epithelial origin. The transmembrane mucin MUC4, is differentially overexpressed in several malignancies, including pancreatic, breast, ovarian, lung, cervical, and head and neck cancers. Of all the aforementioned cancers, the role of MUC4 has been the most thoroughly in pancreatic cancer (PC), which is the 4th leading cause of cancer-related deaths in the United States. While MUC4 is undetectable in the normal or inflamed pancreas (pancreatitis), its expression progressively increases during PC progression and its higher expression correlates with poor survival. The role of MUC4 …

Investigating The Relationship Between Unavoidable, Hospital Acquired Pressure Injury And Mortality: Is Unavoidable, Hospital Acquired Pressure Injury A Signal Of Increased One-Year Mortality Risk?, Eileen Jimenez

Theses & Dissertations

The purpose of this dissertation was to explore the strength of the relationship between unavoidable Hospital Acquired Pressure Injury (HAPI) and increased risk of one-year mortality for patients age 55 and older who were admitted to a hospital from 2015 to 2018. A quantitative, retrospective case-control study was designed to compare demographics, comorbid conditions, pressure injury risk, and living situation of those patients that developed unavoidable HAPI and hospitalized adults with similar physiological burdens that remained injury-free. The one-year mortality for the HAPI group was 27 of 48 (56%), and 26 of 47 patients (55%) for the Control group. The …

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …

The Cellular Origin And Molecular Drivers Of Claudin-Low Mammary Cancer, Patrick D. Raedler

Theses & Dissertations

Breast cancers of the claudin-low subtype make up a substantial portion of triple-negative breast cancers and have stem cell-like and mesenchymal features. Although it has been recognized for some time that this breast cancer subtype is highly aggressive and difficult to treat, the molecular drivers and cellular origin of claudin-low breast cancer have been poorly defined. The lack of suitable in vivo models has prohibited the study of tumor initiation and progression of this subtype. In this work, we report two novel mouse models that, upon expression of oncogenic RAS in the mammary epithelium, develop highly metastatic triple-negative mammary tumors …

Multistrain Hiv-1 Elimination: A Crispr-Cas9 And Theranostics-Based Approach, Jonathan Herskovitz

Theses & Dissertations

A critical barrier to achieving a functional cure for infection by human immunodeficiency virus type one (HIV-1) rests in the presence of latent proviral DNA integrated in the nuclei of host CD4+ T cells and mononuclear phagocytes. Accordingly, HIV-1-infected patients must adhere to lifelong regimens of antiretroviral therapy (ART) to prevent viral rebound, CD4+ T cell decline, and progression to acquired immunodeficiency syndrome (AIDS). Gene editing using clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 technology stands as one means to inactivate integrated proviral DNA. We devised a mosaic gRNA CRISPR-Cas9 system- TatDE- that targets viral transcriptional regulator genes tat / …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Elucidating The Role Of Ecdysoneless In Mrna Processing, Irfana Saleem

Theses & Dissertations

The mammalian orthologue of the evolutionarily conserved Ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression and mitigation of ER stress. However, the molecular mechanisms of ECD function in mammalian cells remain unclear. Here, using mass spectrometry analysis of the mammalian ECD interactome, we identified several components of the mRNA export complexes as binding partners of ECD and then characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A and its associated partners. FISH analysis of Poly-A-tailed mRNAs revealed that ECD depletion/deletion blocks the mRNA export from the nucleus to the cytoplasm. We have …

Influence Of Some Climatic Elements On Radon Concentration In Saeva Dupka Cave, Bulgaria, Peter Nojarov, Petar Stefanov, Karel Turek

International Journal of Speleology

This study reveals the influence of some climatic elements on radon concentration in Saeva Dupka Cave, Bulgaria. The research is based mainly on statistical methods. Radon concentration in the cave is determined by two main mechanisms. The first one is through penetration of radon from soil and rocks around the cave (present all year round, but has leading role during the warm half of the year). The second one is through thermodynamic exchange of air between inside of the cave and outside atmosphere (cold half of the year). Climatic factors that affect radon concentration in the cave are temperatures (air, …

Medical School Watercooler Newsletter - December 17, 2020, Lindsey Lyle

Watercooler Newsletter

This is the December 17, 2020 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• USA scientist named council member of international society
• Student’s poster on vaccinations wins infographic competition
• Faculty needed for the USA College of Medicine Primary Care Pathway Program
• Medical student studies metastatic breast cancer treatment data to improve therapeutic options
• Research aims to improve outlook for Black women with endometrial cancer
• Townsley set to retire at the end of 2020

Healthcare Workers Hospitalized With Covid-19: Outcomes From The Burden Of Covid-19 Study At The University Of Louisville Center Of Excellence For Research In Infectious Diseases [Cerid], Ruth Carrico, T'Shura S. Ali, Maria Hill, Lucia B. Puga Sanchez, Catherine M. Bryan, Dawn Balcom, Stephen P. Furmanek, Amr Aboelnasr, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Introduction: On March 6, 2020, the current ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, reached the commonwealth of Kentucky. Within days, the first cases of infection and hospitalization were identified among healthcare workers (HCW) in Kentucky, other states in the U.S., and around the world. There is little information available regarding the impact of COVID-19 on the HCW population within this area. The objective of this study was to describe the baseline characteristics of hospitalized HCWs infected with COVID-19.

Methods: Data collection was performed as part of a retrospective study of patients hospitalized …

Cultural Identity Formation: A Personal Narrative, Jose Carbajal

Faculty Publications

This paper provides an autoethnography of personal experiences and perceptions of being a minoritized individual. This is the story of a professional social worker learning to adapt to social norms and expectations of self. I discuss the struggles I experienced as an adolescent and as a young adult attending college. This narrative highlights the intersection of faith and social work at moments in my professional development. It is at this intersection that this social worker learns to live a holistic life without feeling discriminated against or ashamed of his identity. I begin to actualize a reality with imperfect beings who …

Conquer And Prevail Issue 45 Dec 17 2020, Wofford College. Office Of Marketing And Communications

Conquer and Prevail Newsletter

No abstract provided.

Lizard And Frog Removal Increases Spider Abundance But Does Not Cascade To Increase Herbivory, Karen H. Beard, Susan L. Durham, Michael R. Willig, Jess K. Zimmerman

Wildland Resources Faculty Publications

Insectivorous vertebrates, especially on islands, can exert top-down control on herbivorous prey, which can transfer through a food chain to reduce herbivory. However, in many systems insectivorous vertebrates feed on more than one trophic level, especially consuming arthropod predators, and this intraguild predation can diminish trophic cascades. Our goal was to determine, using an exclosure experiment, the relative importance of anole lizards and coqui frogs in controlling spider and arthropod abundances as well as herbivory rates in the understory of the Luquillo Experimental Forest, Puerto Rico. We found that exclosures removing both anoles and coquis doubled spider abundance compared to …

Vitas: A Visual Exhibit, Ilisa A. Walter

Art

VITAS is a visual exhibition that addresses the idea of a posthumous legacy. The substance of a person’s life is composed of what they’ve done, and what they become after death is determined by that substance. This exhibition is composed of 25 carved animal skulls and sculptures inspired by the concept of vitas, treating life as an opportunity to advance the next generation through life’s work. VITAS studies the idea of what happens after the passing of a being by applying embellishment, adornment, pigments, and carvings onto the skeletal remains of animals. By applying human influence to natural material, the …

Digital Image Analysis For The Detection Of Group B Streptococcus From Chromid Strepto B Medium Using Phenomatrix Algorithms, Justin Baker, Karen Timm, Matthew Faron, Nathan Ledeboer, Karissa Culbreath

Pathology Research and Scholarship

Group B Streptococcus (GBS) can be found to colonize about 25% of all healthy, adult women and is the leading infectious cause of early neonatal morbidity and mortality in the United States. This study evaluated the clinical performance of PhenoMatrix (PM) chromogenic detection module (CDM) digital imaging software in detection of GBS from LIM broth plated on ChromID Strepto B chromogenic medium (ChromID) using the WASP automated processor. The performance of the PM CDM was compared to manual culture review of the digital images and molecular detection of GBS. ChromID alone had a sensitivity and specificity of 84.5% and 94.7%, …

Challenges Of Using A Blended Learning Approach: A Flipped Classroom In An English Teacher Education Program In Mexico, Edgar Emmanuell Garcia-Ponce, Irasema Mora-Pablo

Higher Learning Research Communications

Objectives: The objective of the study was to understand the views, experiences, and challenges that preservice English teachers perceived in a flipped classroom, which was implemented in a language teacher education program following our institution’s desire to promote blended learning.

Method: Two focus groups were conducted with the students (19). We analyzed the data using thematic analysis.

Results: The results show that the students perceived flipped practices as innovative and beneficial for their learning. However, their responses also reveal that the autonomy required from them and taking more responsibility for their own learning were particularly challenging because of their lack …

Genomic Signatures Of Optimal Growth Temperature In The Family Colwelliaceae, Anais Gentilhomme

Oceanography

The temperature range supporting growth defines a complex physiological phenotype that depends on interactions between an organism's genome and its environment. Its implications are widespread since small changes in optimal growth temperature (OGT) can alter an organism's ability to inhabit an ecological niche. Thus, organisms with extreme thermal growth traits (e.g., psychrophilic, with OGT < 15℃, or thermophilic, with OGT 60 -80℃) may be useful for identifying promising targets when searching for life on other planets, as well as predicting population dynamics in a warming Arctic. We performed comparative genomic analyses of bacteria newly isolated from Arctic sea ice that were affiliated with Colwelliaceae, a family of Gammaproteobacteria that contains many psychrophilic strains, to identify genomic factors that might be used to predict OGT. A phylogenomic analysis of 67 public and 39 newly-sequenced strains, was used to construct an updated phylogenetic tree of Colwelliaceae, of which at least two genera were well represented. To augment the previously reported OGTs of 26 strains, we measured growth rates at −1, 4, 11, and 17 ℃ to determine the OGTs of these 39 new strains of Colwelliaceae. We found that growth rates among all isolates were comparable at −1℃, but varied widely above 10 ℃, indicating higher variability in the ability to tolerate warmer temperatures. To analyze the phenotypic differences on a genomic level, we examined indices of amino acid substitutions that have previously been linked with cold adaptation via an increase in protein flexibility. We found that these indices were significantly correlated with OGT at the whole genome level, although the sign of some correlations were opposite of the predicted positive correlation between temperature and the indices. Using these data, we fit a multiple linear regression model for OGT within the Colwelliaceae family that incorporates the three most informative amino acid indices: GRAVY, Aliphatic Index, and Acidic Residue Proportion. Additionally, a putative cold-adaptive gene cassette was identified that was likely introduced by horizontal gene transfer between two closely related clades with different OGTs. These contributions offer key insights into OGT variability and its underlying genomic foundation in the family Colwelliaceae.

Spatial And Temporal Variability Of Dissolved Aluminum And Manganese In Surface Waters Of The Northern Gulf Of Alaska, Anna R.Y. Kandel

Oceanography

The Northern Gulf of Alaska (NGA) shelf is a productive high-latitude environment where nutrient dynamics are greatly impacted by the seasonal variability in freshwater input and water column mixing. Iron is a key nutrient on the NGA shelf that directly modulates primary production, but inputs are difficult to quantify due to high biological uptake and control exerted by Fe-binding organic ligands. Other lithogenic elements such as aluminum and manganese have the same sources as iron (rivers and sediment) and similar abiotic removal via particle scavenging, but exhibit quasi- conservative behavior in seawater allowing for their use as tracers of these …

Born To Burn: Characterizing Fuel Loads, Flammability And Plant Traits Across Spatio-Temporal Gradients Of Black Spruce Dominated Communities, Emilia J. Grzesik

Biological Sciences

The flammability of black spruce forests is influenced by the fuel loadings and quality of fuels within a site, whereas the ability of a site to self-replace after fire, and thus forest resiliency, depends on the fire-ecological trait attributes of the plant community. Black spruce plant communities have been undergoing self-replacement succession from low to moderate severity fires for thousands of years, however, recent intensification of interior Alaska's fire regime is leading to shifts in post-fire successional trajectories, resulting in many ecological implications. This study focuses on understanding the variation in black spruce forest flammability, based on fuel load quantity …

The Effects Of Individual And Environmental Heterogeneity On Long-Term Population Dynamics Of Cassin's Auklets (Ptychoramphus Aleuticus), Michael E. Johns

Biological Sciences

Reproductive output and survival are expected to be balanced through a tradeoff between current success and future potential, in response to environmental conditions that vary on spatial and temporal scales. Long-term datasets that follow uniquely marked animals through time are excellent tools for describing how heritable or derived traits that influence reproduction and survival can be attributed to individual quality, and how the added reproductive performance of these individuals influence population dynamics. A 37-year record of breeding histories from known-aged Cassin's auklets from Southeast Farallon Island, a colony off the coast of central California, was used to examine these ideas …

Integration Of Remote Sensing Technologies Into Arctic Oil Spill Response, Jessica I. Garron

Interdisciplinary Studies

Identifying the tools and pathways to successful integration of landscape level science into decision-making processes is vital for quality environmental stewardship. Remote sensing information can provide critical facts to decision makers that historically were only available via manned airplane flights and ground truthing expeditions. Remote locations like the Arctic are well suited for monitoring with remote sensing tools due to the lack of transportation infrastructure and communications bandwidth. Remote sensing tools can be valuable when monitoring specific Arctic targets like ocean going vessels, sea ice, coastal erosion, off-shore resource development infrastructure, and oil spills. This dissertation addresses how to mount …

Creating Safety Policy And Procedures In An Active Shooter Event, Mechelle L. Nash

Communication

School and workplace active shootings are on the rise and seem to be the norm today and there is not a working policy in place to train for an active shooter event in our organization, Golden Valley Electric Association. The purpose of this project was to develop a workable policy and procedure for the employees and to enhance the safety culture within our organization. To achieve this goal, a training presentation was created using the ALICE Training Institute’s protocol to train the workforce. The ALICE acronym stands for A=Alert, L=Lockdown, I=Inform, C=Counter, E=Evacuate. Over the course of research for this …

Modeling Permafrost Dynamics And Water Balance Of Arctic Watersheds In A Changing Climate, Matvey Vladimirovich Debolskiy

Geosciences

Changes in climate across the Arctic in recent decades and especially the increase of near-surface air temperature promote signicant changes in key natural components of the Arctic including permafrost (defined as soil experiencing subzero temperature for more than two consecutive years). Recent borehole observations exhibit signicant increase in ground temperatures below the depths of seasonal variations. Modeling studies on a global scale suggest a steady decrease in area underlain by near-surface permafrost in the northern hemisphere in recent decades. Global projections for the next century predict further permafrost degradation depending on the greenhouse gas concentration trajectory. Permafrost degradation is not …