Physiology Commons^™

Rage And Sage: Therapeutic Modalities For Copd, Paul Reynolds

Journal of Undergraduate Research

Funding available through this MEG award has provided an opportunity for me to meet many academic objectives I’ve determined to be important at BYU. We have been successful in conducting pilot studies that reveal possible roles for SAGEs in ameliorating mechanisms of lung inflammation induced by and cigarette smoke (CS). Despite improvement in personal air quality during the past few decades, the rationale for studying mechanisms leading to adverse health effects remains important. This MEG award specifically provided opportunities for students to conduct meaningful research that led to the observation that alveolar epithelial cells and bronchiolar epithelial cells experience elevated …

Nrf2 In Protecting Against Valproic Acid-¬‐Induced Oxidative Injury During Cellular Differentiation, Alyssa Palmer, Jason Hansen

Journal of Undergraduate Research

The causes of the majority of birth defects remain largely unknown today. However, many chemicals known to cause defects are also known inducers of oxidative stress, resulting in faulty cellular function. This suggests an important link between oxidative stress and normal and abnormal embryonic development [1]. Oxidative stress is a phenomenon caused by an imbalance in the production of reactive molecules derived from oxygen called reactive oxygen species (ROS). Although basal levels of ROS are necessary in order for normal cell function to occur, an overabundance of ROS interact with molecules that they shouldn’t, disrupting vital cellular pathways. This is …

Regulation Of Trophoblast Invasion By Pyruvate Kinase Isozyme M2 (Pkm2): Preemptive To Pkm2 Activation Decreases Iugr Symptoms In Mice Exposed To Second-Hand Smoke, Juan Mejia, Juan Arroyo, Ph.D.

Journal of Undergraduate Research

The placenta is an organ composed of highly vascular tissue. It plays an essential role in healthy fetal development as a mediator of gases and nutrients between the mother and fetus. Many complications can occur in this stage of fetal development, such as intrauterine growth restriction (IUGR) when the placenta’s invasive and vascular roles are inhibited. IUGR is an obstetric complication that affects over 10% of the population causing harmful symptoms to the fetus and mother. Physiologically, in the first trimester, high trophoblast cell invasion occurs, and the spiral arteries dilate to create a low resistance, high capacity vessel capable …

Antenatal Exposure To Secondhand Smoke Impacts Growth And Cardiopulmonary Energetics In 4-Week-Old Mice, Kaleb Egbert, Paul Reynolds

Journal of Undergraduate Research

Secondhand smoke (SHS) is a well-established cause of respiratory illness in infants and children who live in environments where exposure is common. Recent studies have been performed to examine the potential effects of SHS exposure on fetus’s before they are born1. The data collected suggests that antenatal exposure to SHS impacts cardiovascular and respiratory function through childhood and may even have lifelong ramifications, even if the exposure is terminated shortly after birth. In our study, we sought to determine the impact of SHS exposure during development in the womb would have on 4 week-old mice, or the equivalent of an …

Microbiota Composition Trends Among High Risk Asd Individuals, Hyrum Eddington, John M. Chaston

Journal of Undergraduate Research

Autism Spectrum Disorder is a neurodevelopmental condition which significantly affects an individual’s social behavior and ability to function in daily living. Although there is a genetic component to the disorder, current research suggests that there are other factors that influence the onset of the disease. One of these factors is the gut microbiota of the individual. Because the human microbiome is a complex system that significantly varies from person to person, finding microbial markers indicative of certain disease can be challenging and problematic. Currently, there are no established protocols that can diagnosis an individual with autism on any criteria save …

An Efficient Method For Generating Conditional Cell Lines For Cellular And Molecular Research, Mark Roth, Dr. Jonathan Alder

Journal of Undergraduate Research

Conditional cell lines are widely used throughout biochemical research. The basic concept is that you can delete a gene you are studying upon the addition of a drug, to cells in culture, and then use the knockout cells to study the genes effects. This process has been facilitated by the advent of the CRISPR/Cas9 system that allows a broad range of genome editing in living cells. Cas9 introduces a double strand break in DNA at a site specified by the CRISPR (guide RNA), and by changing the CRISPR sequence researchers can introduce these double strand breaks almost wherever they want. …

Glutathione-Mediated Oxidative Response In Uvb-Irradiated Hacat Cells, Patrick Badger, Dr. Jason Hansen

Journal of Undergraduate Research

Ultraviolet light (UV) plays a critical role in the etiology of skin cancer, contributing to over 95% of both melanoma and non-melanoma diagnoses. It consists of several wavelengths, among which UVB is the most harmful, causing inflammation associated with sunburn and constituting the principal cause of skin cancer-related death.

B-Hydroxybutyrate Favorably Alters Muscle Cell Survival And Mitochondrial Bioenergetics, Brian Parker, Benjamin Bikman

Journal of Undergraduate Research

The growing worldwide incidence of obesity and its associated pathologies, like type 2 diabetes, has received much deserved attention. However, despite this attention and substantial research efforts, little meaningful progress has been made in slowing or reversing the growing cost and trends of obesity worldwide. As of 2008, almost 10% of medical costs in the United States were incurred due to obesity or other obesity-related diseases,ⁱ with the substantial amount of this cost stemming from the dramatically increased risk of diabetes with excess fat mass.ⁱⁱ According to the US Centers for Disease Control and Prevention, more than one …

Maternal-Fetal Interactions And The Induction Of Preeclampsia By Growth Arrest-Specific 6 (Gas6)/Axl Signaling, Todd Dunaway, Paul Reynolds

Journal of Undergraduate Research

Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure and decreased trophoblast invasion. PE is one of the leading causes of maternal and fetal morbidity and mortality in developed countries. The growth arrest-specific 6 (Gas6) protein is known to induce different responses in cells including prevention of apoptosis and enhanced cell migration and invasion. This protein is secreted in response to growth arrest and it is increased in the serum of PE patients. This discovery suggests a mechanistic role for the Gas6 signaling pathway during PE progression. Gas6 binds to the AXL tyrosine kinase receptor and AXL-mediated …

Elucidating The Role Of The Transcriptional Co-Activator Camta1 In Cardiac Development, Nate Batey, Zach Frederich, Morgan Fronk, Nate Jenkins, Jonathon Hill

Journal of Undergraduate Research

Congenital Heart Disease (CHD) is the most common type of birth defect in the United States, causing more first-year infant deaths than any other birth defect (1). While the causes of CHD are varied, genetic defects are known to play a significant role. Identifying and studying genes involved in embryonic heart development can enhance understanding of the genetic factors in CHDs. The camta1 gene is a promising candidate due to its transient expression in heart morphogenesis and its relationship to camta2 , the only other member of its family in vertebrates and a known player in adult heart failure (2,3).

“Seeing” Beyond The Knees: Inflammation In The Eye As A Result Of Mechanical Stress, Michael Goodman, David Kooyman

Journal of Undergraduate Research

A correlation between Osteoarthritis (OA), affecting over 27 million people in the US [1], and metabolic syndrome (MS), affecting over 340 million people worldwide [2], becomes strikingly important as the search for an effective treatment for OA continues. Increasing evidence has shown that OA is linked to systemic inflammation and MS. With MS comes other substantial comorbidities, including diabetic retinopathy (DR). Ocular inflammation promoted through mechanically induced OA would provide evidence that mechanical stress can be a factor leading to systemic inflammation. Such results would have profound impacts upon the way we view OA as a metabolic disorder, leading to …

Rage Functions During Secondhand Smoke-Induced Bronchopulmonary Dysplasia, Brent Kimber, Dr. Paul Reynolds

Journal of Undergraduate Research

Bronchopulmonary Dysplasia (BPD) is a common respiratory disease among pre-term infants or newborns exposed to harmful toxins during pregnancy or at birth. This leads to several respiratory diseases later in life such as chronic obstructive pulmonary disorder (COPD) or asthma. However, research on the effects of cigarette smoke in utero has many gaps. This project focuses on developing a transgenic mouse model that mimics the pulmonary morphologies and characteristics of BPD. This model will then be used for further research and potentially discover new therapeutic methods for BPD. The transgenic mouse was established using a modified genetic scheme whereby the …

Trf1 Mutations As A Mechanism For Telomere Length Maintenance In Cancer, Collin Sanderson, Jonathan Alder

Journal of Undergraduate Research

Telomeres are repetitive DNA sequences found on the ends of chromosomes that serve to protect the genes contained within each chromosome. As a cell replicates, its telomeres shorten, eventually triggering cellular senescence or death. This serves as a tumor suppressive mechanism by limiting the proliferation of cells. All cancers must overcome this growth limitation by acquiring mutations that permit telomere elongation. Most cancers achieve this by acquiring activating-mutations in an enzyme known as telomerase. Some cancers do not express telomerase, and maintain their telomeres by other means including a mechanism called “alternative lengthening of telomeres” (ALT). However, there exists a …

Examining The Potential Role Of Gpr18 And Gpr119 In Learning And Memory, Brandon Anderson, James Kranewitter-Call, Dr. Jeffrey Edwards

Journal of Undergraduate Research

Many mental disorders plague our society. Dementia and Alzheimer’s disease have greatly impacted many victims and their families. Despite the seriousness and pervasiveness of Alzheimer’s, there is still no effective treatment for it nor the accompanying dementia. GPR18 and GPR119 are G-protein coupled receptors (GPRs) and have been identified in the central nervous system, but their functional role is unknown. Many successful drugs target GPR proteins, so examining these GPRs’ function in the brain could lead to potential targets leading to innovative medical advances.

Memory is dependent on a molecular process called synaptic plasticity. In synaptic plasticity, the strength of …

Forward Genetic Screen To Identify Novel Genes Involved In Nhej Dna Repair, Taylor Brown, Dr. Jonathan Alder

Journal of Undergraduate Research

DNA contains all the information a cell needs to grow, divide, differentiate, and survive. It also dictates how and when a cell should die. DNA damage (particularly double strand breaks i.e. DSBs) may lead to cell death and/or disease. To circumvent DNA breaks, cells use various DNA repair mechanisms including non-homologous end joining (NHEJ). My ORCA research project focused on identifying novel genes involved in NHEJ. I did this by performing a forward genetic screen (FGS) that tested every known gene in the genome for involvement in NHEJ.

Synaptic Modification Of Inhibitory Inputs To Gaba Neurons In The Ventral Tegmental Area: A Novel Potential Target Mediating Reward And Addiction In The Brain, Jeff Edwards

Journal of Undergraduate Research

The objectives of this award were met, especially in regard to the mentoring focus of the award. The students have been mentored and trained in an effective manner as outlined in my Mentoring Plan (abbreviated below). This includes mentoring students in research, writing, publishing, presenting at conferences, etc. Indeed, one measure of the success of mentoring is demonstrated by the fact that all the students graduating from my lab during this time were accepted to the professional school of their choice (see students listed below). Research, especially where the students are actually involved in all aspects of it including data …

The Role Of Lkb1 In Obesity-Induced Skeletal Muscle Inflammation And Insulin Resistance, David Thomson

Journal of Undergraduate Research

The incidence of obesity and the health consequences that accompany it have increased rapidly over the past decade. Understanding the molecular pathways involved in its development will be crucial in developing novel treatment strategies for obesity and associated disorders. Low-grade inflammation likely plays a major role in many of the complications of obesity. We proposed to study the role of liver kinase B1 (LKB1) in the development of inflammation and insulin resistance in obese mice and saturated fatty acid-induced insulin-resistant cells.

A Microfluidic Approach To Measuring Endothelial Cell Migration

Journal of Undergraduate Research

Pathological angiogenesis or new vessel growth plays a key role in a number of diseases including tumor growth and several eye diseases that can lead to blindness. While antiangiogenic therapies have been developed for many of these pathologies, there remains a pressing need for more effective anti-angiogenic therapy with fewer side-effects. Capillary morphogenesis gene 2 (CMG2) has been shown to play an important role in angiogenesis and is a potential target for future anti-angiogenic therapies. To better understand the physiological role of CMG2 and to accurately compare how well different CMG2 antagonists inhibit endothelial cell migration (the putative mechanism for …

Elucidation Of Mechanisms Whereby Embryonic Chicken Limbs Develop, James Broadbent, Jeffery Barrow

Journal of Undergraduate Research

As established by John Saunders 60 years ago, the AER is required for limb growth and patterning. However, the mechanisms whereby the AER regulates these processes remain poorly understood. My professor and I propose that one of the primary roles of the AER is to regulate directional growth of the adjacent limb mesenchyme. Over time, the AER extends along the anteroposterior (AP) and thins along the dorsoventral (DV) axes. These results highlight a morphogenetic paradigm: the dimensions of recruitment signaling centers ultimately shape organs. This model also provides mechanistic insight for evolutionary change. We also show that sonic hedgehog (Shh) …

Development Of A Directed Forward Genetic Screen Using Crispr Libraries, Robert C. Russell, Johnathon Hill

Journal of Undergraduate Research

Thousands of genes control the development of our bodies. These genes must be activated at the proper place and time in order for development to proceed correctly. The technique that we are developing will improve our ability to identify such genes, thus providing insights to the mechanisms underlying development processes. One in 33 live births in the United States is impacted by a birth defect. Of these, congenital heart defects (CHDs) are the most common, affecting nearly 1% of births in the United States.1 For this reason, we are developing a technique that will identify key contributors in heart development.

Understanding Birth Defects By Establishing Glutathione Ontogeny In A Chick Embryo Model, Ryan Mackay, Dr. Jason Hansen

Journal of Undergraduate Research

Most chemicals known to cause birth defects have been shown to induce oxidative stress – a disruption in intracellular redox signaling. The overall purpose of this research is to better understand how environmental/chemical insults that cause oxidative stress result in specific malformations. Since the tripeptide glutathione (GSH) is an abundant antioxidant and important mediator in redox state and signaling, the goal of this project was to measure levels of glutathione during early embryonic development in order to determine when embryos are more susceptible to environmental and chemical stresses. Changes in the amount of GSH will affect the sensitivity of cells …

Combating Anemia And Other Iron Related Deficiencies Through Iron- Efficiency In Soybeans, Miranda Ruth, Bryan Hopkins

Journal of Undergraduate Research

Plants uptake iron from the soil in a variety of ways. Dicots, like soybeans, primarily exude hydrogen (H+) ions and chemical reductants from their roots, which acidify the root zone and reduce Fe³⁺ to Fe²⁺ that can then be utilized by the plant (Brown and Jolley 1989). Iron efficiency in soybeans results in increased dietary iron for those eating the beans. Anemia, which is due to a dietary lack of iron, is an extremely serious health problem that affects much of the world, especially developing countries. Globally, over 30% of the world suffers from this lack of dietary …

Soil Water And Temperature Effects On Resilience Resistance Of Sagebrush Steppe Plant Communities, Trevor Gruwell, Bruce Roundy

Journal of Undergraduate Research

Project Purpose-The purpose of this project was to evaluate the effects of environmental factors on overall resistance and resilience of the sagebrush steppe community. Resistance is defined as a system’s ability to avoid change after a disturbance has taken place and resilience is defined as the ability of a system to return to its natural state after a disturbance has taken place.

The Efficacy Of Tgfβ Inhibition Via Sgi-1252 In The Prevention And Reversal Of Diet-Induced Obesity And Diabetes, Blake Dallon, Benjamin Bikman

Journal of Undergraduate Research

The growing worldwide incidence of obesity and its associated pathologies, like type 2 diabetes, has received much deserved attention. However, despite this attention and substantial research efforts, little meaningful progress has been made in slowing or reversing the growing cost and trends of obesity worldwide.

As of 2008, almost 10% of medical costs in the United States were incurred due to obesity or other obesity-related diseases¹, with a substantial amount of this cost stemming from the dramatically increased risk of diabetes with excess fat mass². According to the US Centers for Disease Control and Prevention, more …

Effects Of Muscle Cooling On Ampk And Protein Synthesis In Skeletal Muscle, Kyle Lyons, David Thomson, Pdbio

Journal of Undergraduate Research

AMP-activated protein kinase (AMPK) is an intracellular protein that regulates many signaling responses including the mechanistic target of rapamycin (mTOR) pathway, which increases protein synthesis1. Recent research suggests that cold-water immersion of the leg activates AMPK in skeletal muscle. It is not known whether cold directly activates AMPK in skeletal muscle or if the aforementioned results are due to systemic or hormonal responses. Furthermore, the direct effect of cooling on protein synthesis-related signaling in skeletal muscle has not been established. If cooling affects the activation of AMPK, then it could also affect mTOR. Therefore, the purpose of this study was …

Using A Tnp Fluorophore To Identify Adenosine Binding In The Snap25b Snare Binding Protein, David Hallan, Dixon Woodbury

Journal of Undergraduate Research

Vesicle fusion is a key step in the cellular process of exocytosis and is at the center of neurotransmitter release by neurons. Fusion is driven by a set of proteins known as SNAREs which includes the protein SNAP25B.

In the synthesis and spectroscopic analysis of the SNAP25B protein, a strong, unexpected 260 nm peak has been seen. This 260 nm peak might correspond to DNA, RNA, or any other adenosine-containing molecule binding to SNAP25B. Previous work indicated that the 260 peak was not due to DNA or RNA. SNAP25B binding to an adenosine-containing substance could be the basis of an …

Drunken Membranes: Short-Chain Alcohols Alter Fusion Of Liposomes To Planar Lipid Bilayers, Jason Paxman, Dixon Woodbury

Journal of Undergraduate Research

The focus of my project was on understanding the effect of alcohol on the complex process of neural transmission, or how the body sends and receives signals through neurons. This essential communication occurs at junctions where neurons meet known as synapses. Essential to the process of sending any signal is the releasing of neurotransmitters into the synapse where they bind to receptors on the adjacent neuron. This releasing of neurotransmitter occurs through a process known as exocytosis. Exocytosis can only occur when neurotransmitter-containing vesicles fuse to the cell membrane. Alterations to the process of exocytosis can result in drastic consequences, …

Diverse Tissue And Organ Systems Differs Following Exposure To Secondhand Cigarette Smoke, Jason Gassman, Dr. Paul R. Reynolds

Journal of Undergraduate Research

The receptor for advanced glycation end-products (RAGE) is a pattern recognition receptor expressed in many cell types, including smooth muscle cells, fibroblasts, macrophages, and epithelial cells (1). RAGE is capable of binding a variety of endogenous ligands, included advanced glycation end-products (AGEs), S100/calgranulins, amyloid-beta peptides, and HMGB1 (2). RAGE signaling has been identified as a primary mediator in a variety of feed-forward inflammatory pathways and, as such, has been implicated in a variety of chronic conditions of inflammation such as chronic obstructive pulmonary disease (COPD), pancreatitis, and diabetic cardiomyopathy (3-5).

Localization Of Cell Bodies Of The Stellate And Superior Cervical Ganglia In Relation To Innervation Of Cardiac Muscle And Vasculature Of The Brain, Alistair Hilton, Jonathan J. Wisco

Journal of Undergraduate Research

Introduction: Arrhythmia is a serious heart defect that effects 14 million people in the United States.i When the impulse rhythm becomes irregular or the frequency of atrial and ventricular beats are different it is called arrhythmia.ii The most serious effects of arrhythmia include sudden cardiac arrest and stroke.iii Sympathetic nerve activity from the stellate ganglia increases prior to arrhythmia events leading to sudden cardiac death.iv About 383,000 cases of cardiac arrest are recorded annually in the United States alone.v Current treatment for arrhythmia consists of ablation or intentional, permanent scarring of the heart tissue, rather than a more targeted block …

Neofunctionalization Of Dual-Targeted Plant Organelle Dna Replication Proteins

Journal of Undergraduate Research

Neofunctionalization is the process by which genes gain a new or modified function as a result of gene duplication and modification of one or more of the new genes. This exciting area of research helps explain the diversification of protein functions in cells. The number of documented examples has increased in recent years in all classes of organisms (Deng et al., 2010; Han et al. 2011; Cannela et al. 2014; Sakuma et al. 2013; Zhang et al. 2014). In some cases a protein that was previously thought to function in only one cellular compartment has been shown to also function …