Digital Commons Network^™

Analysis Of Differential Mrna And Mirna Expression In An Alzheimer’S Disease Mouse Model, Amanda Hazy, Matthew Dalton

Other Undergraduate Scholarship

Research has shown that changes in gene expression play a critical role in the development of Alzheimer’s Disease (AD). Our project will evaluate genome-wide RNA expression patterns from brain and blood in an AD mouse model. This analysis will provide insight regarding the mechanisms of AD pathology as well as determine a possible diagnostic tool utilizing RNA expression patterns found in the blood as biomarkers for AD.

Management Of A Dka Patient With Severe Metabolic And Ketoacidosis With Chronic Renal Insufficiency, Brian Albany

Nursing Student Class Projects (Formerly MSN)

Diabetic ketoacidosis (DKA) serves as one the leading causes of mortality in diabetic patients [14]. The mortality has decreased over the past several decades due to the rapid recognition of the disease state and the improvement of management of DKA [14]. Despite a decline in mortality rates over the past twenty years from 7.96% to 0.67%, errors in management of the disease state are associated with significant morbidity and mortality [2]. Utilization of DKA protocols in the acute care setting have allowed congruency in care and delivery of effective lifesaving treatment. Despite advances in standardized DKA protocols, there still remains …

The Pathophysiology Of Tumor Lysis Syndrome In Oncology Patients, Jessica Richardson

Nursing Student Class Projects (Formerly MSN)

Patients with oncological conditions are at an increased risk of developing a wide variety of complications from chemotherapy that they would not otherwise be exposed too. One such life threatening complication is tumor lysis syndrome, which is an oncology emergency that frequently lands patients in the intensive care unit. Tumor lysis syndrome (TLS) occurs most frequently after the initiation of chemotherapy or other chemotoxic drugs during the patients’ treatment course [8]. It causes faster than normal tumor cell breakdown and release of intracellular contents into the general circulation. [8]. This leads to a very predictable development of electrolyte imbalances to …

Understanding The Mystery Of Brain Death, Natalie A. Felter

Nursing Student Class Projects (Formerly MSN)

Lack of understanding of brain death has contributed to recent controversial cases (Copnell, 2014). The cases of Jahi McMath and Marlise Munoz were the focus of national news, causing an intense debate among the public and healthcare professionals (Copnell, 2014). The concept of brain death is a mystery to the public (Powell, 2014). Copnell (2014) found that 60% of family members who had been told their loved one was brain dead believed that they were still alive. Health professionals not having a clear grasp of brain death’s definition and assessment can lead to increased confusion in family members (Powell, 2014).

Effects Of Edmr On Veterans With Ptsd, Beth Abele

Nursing Student Class Projects (Formerly MSN)

Of all the mental health disorders, the most commonly diagnosed among Iraqi and Afghanistan wars is Posttraumatic stress disorder (PTSD) (Hellmuth et al., 2012). Veterans who are suffering the effects of PTSD are treated every day in VA Medical Centers across the country, as well as in private sector hospitals. Many of these men and women are battling with drug addictions and alcohol abuse in attempts to self medicate (Murdoch et al., 2010). According to nationally represented study by Murdoch and colleagues (2010), one fifth of individuals who have been diagnosed with PTSD use drugs, alcohol or both to treat …

Acute Respiratory Distress Syndrome, Jaqueline Yunker

Nursing Student Class Projects (Formerly MSN)

Acute Respiratory Distress Syndrome is an inflammatory response resulting from injury to the alveolar-­‐capillary membrane. This injury is caused by a systemic inflammatory response that involves either direct trauma to the lung cells, such as a pneumonia, or indirect, such as sepsis. The inflammatory response that is triggered results in leaky alveolar-­‐capillary beds and infiltration of the lungs (Villar, 2011). This is very common with approximately 150,000 cases annually in the United States and a very high mortality rate of 60,000 deaths per year (Pipeling & Fan, 2010). Despite the high mortality rate, 15-­‐35%, there is no set of guidelines …

Myasthenia Gravis: A Closer Look, Erin L. Ricker

Nursing Student Class Projects (Formerly MSN)

Myasthenia gravis (MG) is a rare, chronic autoimmune disease that affects the neurotransmitter acetylcholine and the acetylcholine receptors at the neuromuscular junction (Mestecky, 2013). MG causes fluctuating skeletal muscle weakness and fatigue. According to the Myasthenia Gravis Foundation of America (MGFA) (2010), 20 per 100,000 patients are diagnosed with MG, although researchers believe several more patients are misdiagnosed or missed entirely. Several neurological disorders have similar clinical presentations to MG making it difficult for inexperienced practitioners to identify and properly diagnose patients. Patients are often misdiagnosed and delayed proper treatment for one to two years after initial presentation of symptoms …

Enterovirus: What Everyone Should Know, Debra Mccorkle

Nursing Student Class Projects (Formerly MSN)

Enterovirus is capturing the attention of everyone; but what is it, who is affected by it, and can it be treated and/or prevented? Like any virus the enterovirus has many different strains. The strain capturing everyone’s attention lately is human enterovirus 68 (HEV68). This strain was first detected in California in 1962 (Oberste et al., 2004). Most cases of HEV68 are mild and do not require medical attention, however some can become severe and may cause serious heart or brain infections according to the Center for Disease Control and Prevention (CDC) website (Updated September 8, 2014). HEV68 is a respiratory …

The Role Of Brain-Derived Neurotrophic Factor In Depression, Katie Mendez

Nursing Student Class Projects (Formerly MSN)

According to The World Health Organization, depression is the fourth leading cause of total disease burden and the leading cause of disability worldwide. In the United States, results from the National Health and Nutrition Examination Survey reflect a 16.2% lifetime depression prevalence. Symptoms of depression can range from mild to severe and can be episodic or chronic. Depression has a high rate of comorbidity with multiple chronic diseases and other mental health disorders, predominately anxiety. Unfortunately, few Americans diagnosed with depression actually receive sufficient treatment and symptom management. Previous research has shown that individuals are more likely to seek treatment …

Incretin Hormones And Their Effects In Type 2 Diabetes, Molly Getz

Nursing Student Class Projects (Formerly MSN)

Type 2 diabetes mellitus (T2DM) is a progressive disease characterized as having pancreatic β-cell dysfunction, insulin resistance and hyperglycemia (Stephens, 2010, p. 491). T2DM affected 29.1 million Americans or 9.3% of the population in 2012 and was the seventh leading cause of death in the United States in 2010 ("ADA Statistics," 2014), with many of these patients finding it difficult to achieve or maintain adequate glycemic control despite making lifestyle changes and pharmacologic interventions (Freeman, 2007). Disease management of T2DM requires a comprehensive plan including medication therapy, education and active involvement of the patient, with the goal of therapy to …

Diagnosis, Pathophysiology, And Clinical Treatment Of A Patient With A Pheochromocytoma, Tricia L. Hale

Nursing Student Class Projects (Formerly MSN)

Hypertension is an extremely common diagnosis today. This condition can be caused by a multitude of factors, and can inversely cause numerous unfavorable processes in the body. One rare but significant source of hypertension is a tumor known as a pheochromocytoma, or PCC. This usually benign tumor is most often located on an adrenal gland, and can have a grave impact on the cardiovascular system. The tumor intermittently secretes an excess of the catecholamine norepinephrine, and if large enough, also secretes epinephrine [9]. These episodic bursts can cause extreme hypertension and tachycardia, leading to, at times fatal results. By understanding …

Enterococcus Faecalis Endocarditis: A Case Study, Torri Curtis

Nursing Student Class Projects (Formerly MSN)

Infectious endocarditis is an uncommon disease of the heart stemming from a bacterial or fungal infection on the endocardial surface of the heart or heart valve (Pierce, Calkins, & Thornton, 2012). From review of the literature, infective endocarditis is fairly uncommon and may be difficult to initially diagnose. Per Sabe, Shrestha, and Menon, occurrence of infective endocarditis (IE) is nearly 0.9-6.2 per 100,000 persons per year (2013). Several preexisting conditions such as aging, heart valve disease, implantable cardiac devices, a history of heart disease such as rheumatic fever, and invasive procedures can put a patient at higher risk for IE …

Marshall University Joan C. Edwards School Of Medicine, Professional Enhancement Newsletter, Fall 2014, Darshana Shah Ph.D

Professional Enhancement News (PEN)

Fall 2014, Volume 6, Number 2

Developmental Stress, Condition, And Birdsong: A Case Study In Song Sparrows., Kim L Schmidt, Elizabeth A Macdougall-Shackleton, Shawn P Kubli, Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers. Here, we review data on the relationships between birdsong, a sexually selected trait, and developmental and current condition of birds from a long-term study of a population of song sparrows (Melospiza melodia). Field studies of free-living birds indicate that the …

Differences In Brainstem Level Encoding Of Am And Fm Signals In A Rat Model For Dyslexia, Stephen Anthony Chabot

Open Access Theses

Developmental dyslexia is a language learning disorder that affects a significant portion of the population. Many subjects who suffer from dyslexia show auditory processing deficits as children, some of which persist into adulthood, which impair their ability to learn one or more aspects of language. There is evidence that some types of training can correct the auditory processing deficits and bring the subject to a normal reading or speaking proficiency for their age group. One common rodent model for dyslexia is the cortical freeze lesion model. This model induces a lesion in the rat cortex similar to the microgyria present …

Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu

Open Access Dissertations

Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …

Ethanol-Induced Oxidant Stress Modulates Hepatic Autophagy And Proteasome Activity., Terrence M. Donohue, Paul G. Thomes

Journal Articles: Biochemistry & Molecular Biology

In this review, we describe research findings on the effects of alcohol exposure on two major catabolic systems in liver cells: the ubiquitin-proteasome system (UPS) and autophagy. These hydrolytic systems are not unique to liver cells; they exist in all eukaryotic tissues and cells. However, because the liver is the principal site of ethanol metabolism, it sustains the greatest damage from heavy drinking. Thus, the focus of this review is to specifically describe how ethanol oxidation modulates the activities of the UPS and autophagy and the mechanisms by which these changes contribute to the pathogenesis of alcohol-induced liver injury. Here, …

Contribution Of Teg49 Small Rna In The 5′ Upstream Transcriptional Region Of Sara To Virulence In Staphylococcus Aureus, Samin Kim, Dindo Reyes, Marie Beaume, Patrice Francois, Ambrose Cheung

Dartmouth Scholarship

High-throughput RNA sequencing technology has found the 5' untranslated region of sarA to contain two putative small RNAs (sRNAs), designated teg49 and teg48. Northern blot analysis disclosed that teg49 and teg48 were detectable within the P3-P1 and P1 sarA promoter regions, respectively. Focusing on teg49, we found that this sRNA, consisting of 196 nucleotides, is transcribed in the same direction as the sarA P3 transcript. The expression of both P3 and teg49 transcripts is dependent on sigB and cshA, which encodes a DEAD box RNA helicase. Within the sRNA teg49, there are two putative hairpin-loop structures, HP1 and HP2. Transversion …

Dynamics Of Alpha Control: Preparatory Suppression Of Posterior Alpha Oscillations By Frontal Modulators Revealed With Combined Eeg And Event-Related Optical Signal, Kyle E. Mathewson, Diane M. Beck, Tony Ro, Edward L. Maclin, Kathy A. Low, Monica Fabiani, Gabriele Gratton

Publications and Research

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously, we proposed that alpha (8–12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top–down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently recorded EEG, while participants performed a visual target detection …

Effect Of Obesity And Exercise On The Expression Of The Novel Myokines, Myonectin And Fibronectin Type Iii Domain Containing 5, Jonathan M. Peterson, Ryan Mart, Cherie E. Bond

ETSU Faculty Works

Metabolic dysfunction in skeletal muscle is a major contributor to the development of type 2 diabetes. Endurance exercise training has long been established as an effective means to directly restore skeletal muscle glucose and lipid uptake and metabolism. However, in addition to the direct effects of skeletal muscle on glucose and lipids, there is renewed interest in the ability of skeletal muscle to coordinate metabolic activity of other tissues, such as adipose tissue and liver. The purpose of this study was to examine the effects of endurance exercise on the expression level of two novel muscle-derived secreted factors, or myokines, …

Withaferin A Alone And In Combination With Cisplatin Suppresses Growth And Metastasis Of Ovarian Cancer By Targeting Putative Cancer Stem Cells., Sham S. Kakar, Mariusz Z. Ratajczak, Karen S. Powell, Mana Moghadamfalahi, Donald M. Miller, Surinder K. Batra, Sanjay K. Singh

Journal Articles: Biochemistry & Molecular Biology

Currently, the treatment for ovarian cancer entails cytoreductive surgery followed by chemotherapy, mainly, carboplatin combined with paclitaxel. Although this regimen is initially effective in a high percentage of cases, unfortunately within few months of initial treatment, tumor relapse occurs because of platinum-resistance. This is attributed to chemo-resistance of cancer stem cells (CSCs). Herein we show for the first time that withaferin A (WFA), a bioactive compound isolated from the plant Withania somnifera, when used alone or in combination with cisplatin (CIS) targets putative CSCs. Treatment of nude mice bearing orthotopic ovarian tumors generated by injecting human ovarian epithelial cancer cell …

Evaluation Of A New Method Of Fossil Retrodeformation By Symmetrization: Crania Of Papionins (Primates, Cercopithecidae) As A Test Case, Melissa Tallman, Andrea Morrow, Nina Amenta, Eric Delson, Stephen Frost, Deboshmita Ghosh, Zachary Klukkert, Gary Sawyer

Open Access Publishing Support Funded Articles

Diagenetic distortion can be a major obstacle to collecting quantitative shape data on paleontological specimens, especially for three-dimensional geometric morphometric analysis. Here we utilize the recently -published algorithmic symmetrization method of fossil reconstruction and compare it to the more traditional reflection & averaging approach. In order to have an objective test of this method, five casts of a female cranium of Papio hamadryas kindae were manually deformed while the plaster hardened. These were subsequently “retrodeformed” using both algorithmic symmetrization and reflection & averaging and then compared to the original, undeformed specimen. We found that in all cases, algorithmic retrodeformation improved …

Inpp4b Suppresses Prostate Cancer Cell Invasion, Myles C. Hodgson, Elena I. Deryugina, Egla Suarez, Sandra M. Lopez, Dong Lin, Hui Xue, Ivan P. Gorlov

Dartmouth Scholarship

INPP4B and PTEN dual specificity phosphatases are frequently lost during progression of prostate cancer to metastatic disease. We and others have previously shown that loss of INPP4B expression correlates with poor prognosis in multiple malignancies and with metastatic spread in prostate cancer.

We demonstrate that de novo expression of INPP4B in highly invasive human prostate carcinoma PC-3 cells suppresses their invasion both in vitro and in vivo. Using global gene expression analysis, we found that INPP4B regulates a number of genes associated with cell adhesion, the extracellular matrix, and the cytoskeleton. Importantly, de novo expressed INPP4B suppressed the proinflammatory chemokine …

“Me & My Brain”: Exposing NeuroscienceʼS Closet Dualism, Liad Mudrik, Uri Maoz

Psychology Faculty Articles and Research

Our intuitive concept of the relations between brain and mind is increasingly challenged by the scientific world view. Yet, although few neuroscientists openly endorse Cartesian dualism, careful reading reveals dualistic intuitions in prominent neuroscientific texts. Here, we present the “double-subject fallacy”: treating the brain and the entire person as two independent subjects who can simultaneously occupy divergent psychological states and even have complex interactions with each other—as in “my brain knew before I did.” Although at first, such writing may appear like harmless, or even cute, shorthand, a closer look suggests that it can be seriously misleading. Surprisingly, this confused …

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …

Swimming Against The Tide: Investigations Of The C-Bouton Synapse, Adam S. Deardorff, Shannon H. Romer, Patrick M. Sonner, Robert E. W. Fyffe

Neuroscience, Cell Biology & Physiology Faculty Publications

C-boutons are important cholinergic modulatory loci for state-dependent alterations in motoneuron firing rate. m2 receptors are concentrated postsynaptic to C-boutons, and m2 receptor activation increases motoneuron excitability by reducing the action potential afterhyperpolarization. Here, using an intensive review of the current literature as well as data from our laboratory, we illustrate that C-bouton postsynaptic sites comprise a unique structural/functional domain containing appropriate cellular machinery (a “signaling ensemble”) for cholinergic regulation of outward K⁺ currents. Moreover, synaptic reorganization at these critical sites has been observed in a variety of pathologic states. Yet despite recent advances, there are still great challenges …

The Association Of The Vanin-1 N131s Variant With Blood Pressure Is Mediated By Endoplasmic Reticulum-Associated Degradation And Loss Of Function, Ya-Juan Wang, Bamidele O. Tayo, Anupam Bandyopadhyay, Heming Wang, Tao Feng, Nora Franceschini, Hua Tang, Jianmin Gao, Yun Ju Sung, The Cogent Bp Consortium, Robert C. Elston, Scott M. Williams, Richard S. Cooper, Ting-Wei Mu, Xiaofeng Zhu

Dartmouth Scholarship

High blood pressure (BP) is the most common cardiovascular risk factor worldwide and a major contributor to heart disease and stroke. We previously discovered a BP-associated missense SNP (single nucleotide polymorphism)–rs2272996–in the gene encoding vanin-1, a glycosylphosphatidylinositol (GPI)-anchored membrane pantetheinase. In the present study, we first replicated the association of rs2272996 and BP traits with a total sample size of nearly 30,000 individuals from the Continental Origins and Genetic Epidemiology Network (COGENT) of African Americans (P = 0.01). This association was further validated using patient plasma samples; we observed that the N131S mutation is associated with significantly lower plasma vanin-1 …

Activation Of C-Myc And Cyclin D1 By Jcv T-Antigen And Β-Catenin In Colon Cancer, Michael J. Ripple, Amanda Parker Struckhoff, Jimena Trillo-Tinoco, Li Li, David A. Margolin, Robin Mcgoey, Luis Del Valle

School of Medicine Faculty Publications

During the last decade, mounting evidence has implicated the human neurotropic virus JC virus in the pathology of colon cancer. However, the mechanisms of JC virus-mediated oncogenesis are still not fully determined. One candidate to mediate these effects is the viral early transcriptional product T-Antigen, which has the ability to inactivate cell cycle regulatory proteins such as p53. In medulloblastomas, T-Antigen has been shown to bind the Wnt signaling pathway protein β-catenin; however, the effects of this interaction on downstream cell cycle regulatory proteins remain unknown. In light of these observations, we investigated the association of T-Antigen and nuclear β-catenin …

Expression Of Peroxiredoxin 1 And 4 Promotes Human Lung Cancer Malignancy, Hong Jiang, Lisha Wu, Murli Mishra, Hedy A. Chawsheen, Qiou Wei

Toxicology and Cancer Biology Faculty Publications

Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated. In this study we analyzed the expression of 2-Cys Prxs in lung cancer, and examined their levels of expression in a variety of cell lines established from human lung …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …