Medical Sciences Commons^™

Investigating Localization And Activity-Dependent Translation Of Astrocyte Mrna, Rohan Khazanchi

Senior Honors Papers / Undergraduate Theses

Over the past two and a half years, I have studied fundamental aspects of astrocyte biology by investigating the existence and mechanism of astrocyte local translation peripherally around tripartite synapses consisting of pre- and post-synaptic neuron terminals and an associated astrocyte. Astrocytes are critical components of central nervous system synapses (which are predominately tripartite in nature); thus, it is important to consider how astrocyte dysregulation and dysfunction could contribute to the pathogenesis of diseases of synaptic connectivity such as autism spectrum disorders, Alzheimer’s disease, seizure disorders, and more. Overall, my projects involved the development of novel methods to identify astrocyte-specific …

Evidence Of Strain Structure In Plasmodium Falciparum Var Gene Repertoires In Children From Gabon, West Africa, K Day, Y Artzy-Randrup, K Tiedje, V Rougeron, Donald S. Chen, T Rask, M Rorick, F Migot-Nabias, P Deloron, A Luty, M Pascual

NYMC Faculty Publications

Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For Plasmodium falciparum, strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as PfEMP1 and encoded by the multicopy multigene family known as the var genes. Deep sampling of the …

The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar

NYMC Faculty Publications

Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …

The Impact Spectrum Of Head Injuries On The Sport Of Hockey, Caleb W. Neal

Senior Honors Projects

The Center for Disease Control and Prevention (CDC) estimates there are between 1.6-3.8 million sports and recreation related concussions per year. In fact there are over 4 million concussions (including non-sports related) in total each year. A concussion is defined as a serious brain injury caused by the rapid movement (linear front-to-back, side-to-side) or rotational (angular) movement of the brain inside the skull, which results in damage and disruption to the brain cell function, causing brain trauma (sports concussion library). Sports-related concussions (SRCs) are concussions that are specifically sustained during a sporting event. The sport with the highest incidence of …

Humor In Medicine: A Literature Review Of Humor’S Potential Therapeutic Value In Health Care, Weston Michael Grant

Psychological Science Undergraduate Honors Theses

Using humor and laughter within the health care field has the potential to be relevant to patients during treatment, to the patient-caregiver relationship, to the subjective well-being of health care providers, and to the environments’ (e.g., work settings) impact on group relationships (e.g., colleagues). A review of the literature examines how the psychological and physiological effects of laughter and humor within the human body impact health and well-being, how humor and laughter improve the patient-practitioner relationship, and if humor and laughter can potentially impact physician burnout. Several possible implications for these findings are discussed, such as professional medical comedians, improvements …

Determination Of The Effects That A Previously Uncharacterized Secreted Product From Klebsiella Pneumoniae Has On Citrobacter Freundii And Enterobacter Cloacae Biofilms, Cody M. Hastings

Undergraduate Honors Theses

More so than ever, Multiple Drug Resistant (MDR) bacteria are on the rise due to overuse of antibiotics along with natural selection for adaptations that enhance drug-resistant properties. One particular bacterial family, Enterobacteriaceae, has been problematic, exhibiting several bacterial members that have developed a precipitous resistance to modern antibiotics and are also primary causative agents of nosocomial, or hospital acquired, infections. Citrobacter freundii (CF) and Enterobacter cloacae (ECL) are two species of the Enterobacteriaceae family causing significant medical concern due to their role in producing numerous opportunistic infections such as bacteremia, lower respiratory tract infections, urinary tract infections, and endocarditis. …

Investigating The Mechanism Of Novel Anticancer Agent, As1411 : Does Metabolism To Guanine Play A Role?, Parker T Howard

College of Arts & Sciences Senior Theses

AS1411 is an oligonucleotide that has shown promising results in lab experiments and clinical trials as an anti-cancer drug, Likewise, treatments with guanine based purine compounds (GBPCs) have demonstrated similar anti-proliferative effects in vitro. This activity is dependent on the HGPRT enzyme. Similarities in activity and physical structure has led us to believe that AS1411 and GBPCs operate by a similar mechanism. To test this, we compare the activity of both in the presence of HGPRT siRNAs and HGPRT deficient cells. While siRNA treatment was unable to alter the activity of GBPCs or AS1411 in our cell lines, HGPRT deficient …

Dox Inducible Idh2 R140q Expression In Stem Cells Results In Cell Death, Opposite Of Cancerous Overgrowth, Reuben Hogan

Undergraduate Research Symposium Posters

Mutations in isocitrate dehydrogenase (IDH) 1 or 2 are found in about 23% of acute myeloid leukemia (AML) samples and about 90% of gliomas. Mutations result in neomorphic function of the IDH enzyme that yields the novel molecule 2-hydroxyglutarate (2HG) instead of alpha-ketoglutarate (aKG). 2HG is known to be associated with hypermethylation of DNA and histones, a phenotype seen in AML. Our lab intends to study the mechanism by which hypermethylation is achieved and how this mechanism relates to the onset of cancer. In this experiment, we utilized a line of H9 stem cells which we had developed. These cells …

The Contribution Of Solid Food On Total Water Intake In 3-13 Y Children, Audrey Caroline Smith

Health, Human Performance and Recreation Undergraduate Honors Theses

Introduction: Adequate hydration is important element of good health. Several studies indicate that the majority of kids are hypohydrated and do not meet dietary water intake guidelines. Some scientist also suggest that good hydration might be achieved by large consumption of food that are rich in water (i.e. fruits and vegetables). However, the information of food consumption on total water intake in children is limited.

Purpose: We evaluated the contribution of water from solid food on total water intake in children.

Methodology: For this cross-sectional study 81 children (35 female) 3 to 13 years old were randomly recruited to participate. …

Islet Cell Transplant: Successful Survival Through Pregnancy., Angela Magdaleno, Marc A. Vengrove Do, Facp

Department of Medicine

No abstract provided.

Euglycemic Dka In Mody Patient: Empagliflozin To Blame., Angela Magdaleno, Sandhya Venkataraman Do, Gretchen Perilli Md

Department of Medicine

No abstract provided.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (Dipnech): A Case Presentation And Overview Of Documented Cases (Poster)., Samer Bolis Do, Yehia Y. Mishriki Md

Department of Medicine

No abstract provided.

Trends Of Revascularization In Acute Myocardial Infarction Patients With Coronary Artery Anomalies: A Nationwide Analysis Of 8,131 Patients., Neeraj Shah Md, Vratika Agarwal Md, Nainesh C. Patel Md

Department of Medicine

No abstract provided.

Epigenetic Age Acceleration Assessed With Human White-Matter Images, Karen Hodgson, Melanie A. Carless, Hemant Kulkarni, Joanne E. Curran, Emma Sprooten, Emma E. Knowles, Samuel R. Mathias, Harald H. H. Goring, Nailin Yao, Rene L. Olvera, Laura Almasy, Ravindranath Duggirala, John Blangero, David C. Glahn

School of Medicine Publications

The accurate estimation of age using methylation data has proved a useful and heritable biomarker, with acceleration in epigenetic age predicting a number of age-related phenotypes. Measures of white matter integrity in the brain are also heritable and highly sensitive to both normal and pathological aging processes across adulthood. We consider the phenotypic and genetic interrelationships between epigenetic age acceleration and white matter integrity in humans. Our goal was to investigate processes that underlie interindividual variability in age-related changes in the brain. Using blood taken from a Mexican-American extended pedigree sample (n = 628; age = 23.28-93.11 years), epigenetic …

Trunk And Respiratory Motor Control In Typically Developing Children And Its Implications In Children With Chronic Spinal Cord Injury., Goutam Singh

Electronic Theses and Dissertations

Independent sitting is a major milestone and is also a prerequisite for optimal performance of activities of daily living (ADLs). Development of sitting posture control is a dynamic process involving control of degrees of freedom of head and trunk. Traditionally, trunk has been modeled as a single unit (segment). However, recent studies have suggested that it is made up multiple spinal units, controlled by a combination of trunk muscles. During typical development, posture control of trunk is different for different trunk segments. This motor development of trunk control is a complex process due to constant interaction between the nervous system …

Combating Malignant Melanoma With The Multifaceted Soy-Dervied Peptide Lunasin., Christopher Paul Shidal

Electronic Theses and Dissertations

Lunasin is a 44 amino acid peptide that has been shown to have cancer chemopreventative and chemotherapeutic properties. This study investigated the potential utility of Lunasin as a chemotherapeutic in melanomas. Studies showed that Lunasin had little activity against established melanoma cell lines using adherent culture methods; however, Lunasin’s in vitro activity was significantly higher in non-adherent colony-forming assays and oncosphere formation. These results led to the investigation of whether or not Lunasin has selective effects on cancer initiating cells (CIC) that are known to be present in melanomas. It was revealed that Lunasin selectively inhibited the proliferation of high-ALDH …

Fibulin-4 Is Essential For Maintaining Arterial Wall Integrity In Conduit But Not Muscular Arteries., Carmen M. Halabi, Thomas J. Broekelmann, Michelle Lin, Vivian S. Lee, Mon-Li Chu, Robert P. Mecham

Department of Dermatology and Cutaneous Biology Faculty Papers

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4^E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. …

Elevated Dna Oxidation And Dna Repair Enzyme Expression In Brain White Matter In Major Depressive Disorder, Attila Szebeni, Katalin Szebeni, Timothy P. Diperi, Luke A. Johnson, Craig A. Stockmeier, Jessica D. Crawford, Michelle J. Chandley Health Sciences, Liza J. Hernandez, Katherine C. Burgess, Russell W. Brown, Gregory A. Ordway

ETSU Faculty Works

Background: Pathology of white matter in brains of patients with major depressive disorder (MDD) is well-documented, but the cellular and molecular basis of this pathology are poorly understood.

Methods:Levels of DNA oxidation and gene expression of DNA damage repair enzymes were measured in Brodmann area 10 (BA10) and/or amygdala (uncinate fasciculus) white matter tissue from brains of MDD (n=10) and psychiatrically normal control donors (n=13). DNA oxidation was also measured in BA10 white matter of schizophrenia donors (n=10) and in prefrontal cortical white matter from control rats (n=8) and rats with repeated stress-induced anhedonia (n=8).

Results:DNA oxidation …

Spinal Cord Injury Induced Cardiac Decline And The Limitations Of Exercise., Kathryn Michele Deveau

Electronic Theses and Dissertations

There is a general consensus that the level and the severity of spinal cord injury (SCI) impacts chronic cardiac abnormalities such that high thoracic and cervical SCI are the most severely affected. Furthermore, the extreme degree of immobility/inactivity experienced by the persons with SCI has implications on cardiac decline. Yet it has been difficult to separate the relative contributions of the decentralized autonomic nervous system (ANS) and the immediate and profound inactivity to chronic cardiac abnormalities. As such, this body of work sought to characterize a contusion SCI that results in persistent CV dysfunction. Echocardiography, Dobutamine stress echocardiography and pressure …

Characterization Of A Mutant Oncolytic Adenovirus And The Role Of Jnk In Enhancing Virotherapy., Stephen L. Wechman

Electronic Theses and Dissertations

Oncolytic adenoviruses (Ads) have great therapeutic potential for lung cancer treatment. Cancer selective E1b-deleted Ads are safe; however, their clinical cancer therapeutic efficacy remains limited. The limited efficacy of Ad virotherapy is due to many factors including inefficient cancer cell lysis, Ad release and spread. Progress in overcoming these barriers to Ad virotherapy are hampered by limited knowledge of the genes associated with enhanced Ad release and spread and the dearth of understanding of the mechanisms by which E1b-deleted Ads cause cancer cell lysis. The role of c-JNK n- terminal kinase (JNK) phosphorylation in this process remains unknown. …

The Interaction Of Homoserine Lactones And Paraoxonase 2 Modulates Cell Death Signaling And Cell Proliferation., Aaron Mackallan Neely

Electronic Theses and Dissertations

Pseudomonas aeruginosa produces N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule that functions to facilitate bacteria-bacteria communication. C12 has also been reported to affect many aspects of human host cell physiology, including evoking cell death in various types of cells. However, the signaling pathway(s) leading to C12-triggerred cell death remains unclear. To clarify cell death signaling induced by C12, we examined mouse embryonic fibroblasts (MEFs) deficient in one or more caspases. Our data indicate that, unlike most apoptotic inducers, C12 evokes a novel form of apoptosis in cells, probably through the direct induction of mitochondrial membrane permeabilization. Importantly, C12 induces apoptosis …

The Effects Of Moderate Alcohol Consumption And Inflammation On The Hepatic Matrisome And The Renal Cortex Proteome., Christine E. Dolin

Electronic Theses and Dissertations

Background. The association of chronic ethanol (EtOH) consumption with extracellular matrix (ECM) changes in alcoholic liver disease (ALD) is well established in the context of hepatic fibrosis. However, it is becoming increasingly understood that the hepatic ECM responds dynamically to stress well before fibrosis. The term “transitional tissue remodeling” describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these ECM changes may contribute to early disease initiation and/or progression. The nature and magnitude of these changes to the ECM are currently poorly understood. In contrast to the liver, EtOH …

Targeting The Glucose Metabolism Of Myeloid-Derived Suppressor Cells (Mdscs) To Stimulate Cancer Immunity., Jaspreet Grewal

Electronic Theses and Dissertations

Myeloid derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that are significantly increased in cancer patients and correlate with higher stage and poor prognosis. MDSCs negatively modulate anti-tumor immunity, suppress T cell activity, promote angiogenesis and increase the risk of metastasis. In this study, we report that monocytic-MDSCs (M-MDSCs) but polymorphonuclear-MDSCs (PMN-MDSCs) over-express 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatases 3 (PFKFB3), an important regulator of glycolysis. Furthermore in the melanoma model, M-MDSCs but not PMN-MDSCs suppressed T cell function which correlated with PFKFB3 over-expression and increased rate of glycolysis. PFKFB3 inhibition with the first-in-class small molecule inhibitor, PFK-158 reversed M-MDSC …

An Evaluation Of Gabab Receptors On Modulating Neuroinflammation In A Non-Transgenic Animal Model Of Alzheimer's Disease, Monica Bolton

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and distinct neuropathological hallmarks, including amyloid beta plaques and neurofibrillary tau tangles (NFT). Although the etiology remains to be discovered, several risk factors exist that significantly contribute to developing AD. Diabetes is one of the major risk factors associated with AD and is characterized by disrupted insulin signaling that may contribute to or exacerbate AD pathologies. Furthermore, both disorders result in increased neuroinflammation. Considerable evidence has demonstrated that a chronic inflammatory response, in particular chronic microglia activation, promotes A production as well as the hyperphosphorylation of tau through …

Thermal And Developmental Ecology Of Pupfish, Cyprinodon, Alexander Jones

UNLV Theses, Dissertations, Professional Papers, and Capstones

Pupfish from the genus Cyprinodon are among the most endangered groups of fishes on the planet, with nearly 40% of species being threatened with extinction. These pupfishes are often assumed to be the most temperature tolerant of all fish, coping with temperatures as low as 0 °C and as high as 44 °C. However, conflicting data exist and certain measures of thermal tolerance are not markedly higher in pupfish compared to common game fish. Pupfish egg production and growth has been known to be hampered at temperatures well below what they apparently experience in nature. I addressed why eggs fail …

Characterization Of Novel Cannabinoid Receptor 2-Selective Agonists At The Biochemical And Cellular Levels: Leads For Therapeutic Agents, Ashley M. Hine

Honors Scholar Theses

Putative cannabinoid receptor 2 (CB₂)-selective agonists were identified from a library of commercially available compounds via inhibition of cAMP accumulation in high throughput screening. Binding affinity and receptor subtype selectivity were assessed using heterologous competition binding assays against the known cannabinoid orthosteric ligand CP55940. Test compounds ASX0152383 and CSC003141 preferentially bound to CB₂, with no detection of binding to CB₁ up to 1 mM. CMB038865 exhibited nearly 100-fold selectivity for CB₁ over CB₂, while CZ000026 bound non-preferentially to both receptors in the low micromolar range. To determine the extent of G protein …

The Design Of An Instrument To Assess Clinical Laboratories Efficacy Post Implementation Of The Patient Protection Affordable Care Act, Harry Mcdonald Jr.

Dissertations

The healthcare system in the United States has undergone substantial changes in support of the Patient Protection and Affordable Care Act (PPACA). On March 23, 2010, the implementation of the new healthcare law brought universal healthcare access to all Americans, while attempting to increase quality and decrease medical costs. The new law promotes more of a quality-focused, outcome-based model rather than a pay-for-fee service model; thus, moving the paradigm from infrequent to preemptive healthcare. The PPACA postulates as the only way to achieve cost savings while increasing quality and access. Never before has there been such an extensive change to …

Genome-Scale Precision Proteomics Identifies Cancer Signaling Networks And Therapeutic Vulnerabilities, Hong Wang

Theses and Dissertations (ETD)

Mass spectrometry (MS) based-proteomics technology has been emerging as an indispensable tool for biomedical research. But the highly diverse physical and chemical properties of the protein building blocks and the dramatic human proteome complexity largely limited proteomic profiling depth. Moreover, there was a lack of high-throughput quantitative strategies that were both precise and parallel to in-depth proteomic techniques. To solve these grand challenges, a high resolution liquid chromatography (LC) system that coupled with an advanced mass spectrometer was developed to allow genome-scale human proteome identification. Using the combination of pre-MS peptide fractionation, MS2-based interference detection and post-MS computational interference correction, …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Investigating The Role Of Dispatched In Hedgehog Ligand Transport And Delivery, William Bodeen

Theses and Dissertations (ETD)

During the development of all metazoans, the Hedgehog (Hh) signaling pathway provides instructional cues influencing a variety of cellular processes. The pathway ligand, Hh, is dually lipidated by cholesterol and palmitate, which effectively anchors the molecule to the lipid bilayer of the signal producing cell. To complicate the Hh pathway induction process, the Hh ligand is often produced at a significant distance from the cells it influences. Only one known conserved molecule, Dispatched (Disp), can alleviate the membrane tethering imparted by Hh lipidation. Underscoring the importance of Disp protein during development, knockout animals succumb to lethality at E9.5, an exact …