Medicine and Health Sciences Commons^™

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

The Role Of The Rx3/ Otx Pathway In Zebrafish Eye Development, Navaneetha Krishnan Bharathan

Theses and Dissertations

Colobomas are a type of eye defect characterized by the presence of a hole in certain eye structures. In this study, the roles of the zebrafish Otx genes, otx2 and otx1a, as well as the Rx family gene, rx3, in choroid fissure closure, the disruption of which leads to the onset of colobomas, were studied. It was observed that while the otx2 loss-of-function mutant, otx2hu3237 displayed small colobomas and the otx1a mutant, otx1a6del, did not exhibit any morphological eye defects, zebrafish possessing both mutations presented with a range of colobomas, some of which were more severe than otx2 single mutants …

Glial Cell Modulators And Associated Anti-Inflammatory Activity: Implications In Reducing Methamphetamine Abuse-Related Behaviors In Rodents, Sarah Snider

Theses and Dissertations

Methamphetamine is a psychomotor stimulant that produces hyperactivity and euphoria and can lead to drug-seeking and abuse. An estimate from 2005 put the cost of methamphetamine abuse to society at an estimated 23.4 billion dollars. One of methamphetamine's effects is activation of glial cells and associated neuroinflammatory activity in the periphery and CNS. Glia are responsible for maintaining calcium homeostasis, neuroplasticity, immune activity, and cell signaling. Activation of glia and neuroinflammation are becoming recognized as links in drug abuse-related behavior. The goal of the present work was to assess the ability of ibudilast, AV1013, and minocycline, three glial cell modulating …

Comprehensive Review On The Existence Of Genomic Imprinting In Aves, Derek Gygax

Theses and Dissertations

Genomic imprinting results in monoallelic parent-of-origin gene expression. Therian mammals show conclusive evidence for imprinting, while the evidence in Aves is conflicting. It’s unclear if Aves have the proteins necessary for establishment and maintenance of imprinting loci. Every examined avian orthologue to mammalian imprinted genes shows biallelic expression providing evidence for a lack of imprinting in Aves. While the known parent-of-origin quantitative trait loci in chicken do not overlap with differentiated methylated regions, further analysis with a larger sample size is required. No transcript in the chicken transcriptome at incubation day 4.5 shows parent-of-origin expression, providing strong evidence for a …

Resolving The Titer Of Murine Cytomegalovirus By Plaque Assay Using The M2-10b4 Cell Line And A Low Viscosity Overlay., Katherine A Zurbach, Toktam Moghbeli, Christopher M Snyder

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Murine cytomegalovirus (MCMV) is increasingly used as an infectious model to investigate host-pathogen interactions in mice. Detailed methods have been published for using primary murine embryonic fibroblasts (MEFs) for preparing stocks and determining viral titers of MCMV. For determining the titer of MCMV by plaque assay, these methods rely on a high viscosity media that restricts viral spreading through the supernatant of the culture, but is also usually too viscous to pipet. Moreover, MEFs must be repeatedly generated and can vary widely from batch-to-batch in purity, proliferation rates, and the development of senescence. In contrast, the M2-10B4 bone marrow …

Characterization Of The Discriminative Stimulus Effects Of Nitrous Oxide, Kellianne J. Richardson

Theses and Dissertations

Nitrous oxide (N2O) is a widely used anesthetic adjunct in dentistry and medicine that is also commonly abused. N2O alters the function of several receptors in vitro and ex vivo, however, the receptors systems underlying its abuse-related intoxicating effects are poorly understood. The goals of this dissertation were to (1) establish N2O as a discriminative stimulus, (2) characterize the temporal properties of the discriminative stimulus, (3) determine the degree of similarity between N2O and other inhalants and (4) explore the neurochemical effects responsible for the stimulus properties of N2O. Twenty-four mice were trained to discriminate 10 minutes exposure to 60% …

Redox Triggering Of Podocyte Nlrp3 Inflammasomes And Glomerular Injury In Hyperhomocysteinemia, Justine M. Abais

Theses and Dissertations

Hyperhomocysteinemia (hHcys), an important pathogenic factor contributing to the progression of end-stage renal disease (ESRD), has been shown to activate NOD-like receptor protein 3 (NLRP3) inflammasomes and cause podocyte dysfunction and glomerular sclerosis. hHcys induces aggregation of the three inflammasome components – NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 – and its activation is indicated by increased caspase-1 activity and secretion of interleukin-1β (IL-1β). The aims of the present study sought to elucidate the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-mediated redox signaling in hHcys-induced NLRP3 inflammasome activation, to dissect the contribution of common endogenous reactive oxygen species (ROS) …

Brain Science And Stem Learning, Dennis L. Molfese

Discipline-Based Education Research Group Speaker Series

Brain Science is an interdisciplinary science and as such touches on a host of domains that among others include Behavioral & Social Sciences, Biological Sciences, Computer & Information Science, Economics, Engineering (multiple domains from Electrical to Mechanical to Structural), Education, Human Resources, Engineering, Environmental, Education, Geosciences, Engineering, Mathematical, Physical Sciences, Psychology, and Zoology. The approach provides a means to study matter from an assortment of elements to the integration of complex domains that stretch from the interactions of neuropeptides to conscious thought that cover the lifespan of single cell organisms to humans. We will touch on a few of these …

D_Cdf Test Of Negative Log Transformed P-Values With Application To Genetic Pathway Analysis, Hongying Dai, Richard Charnigo

Manuscripts, Articles, Book Chapters and Other Papers

In genetic pathway analysis and other high dimensional data analysis, thousands and millions of tests could be performed simultaneously. p-values from multiple tests are often presented in a negative log-transformed format. We construct a contaminated exponential mixture model for −ln(P) and propose a D_CDF test to determine whether some −ln(P) are from tests with underlying effects. By comparing the cumulative distribution functions (CDF) of −ln(P) under mixture models, the proposed method can detect the cumulative effect from a number of variants with small effect sizes. Weight functions and truncations can be incorporated to the D_CDF test to improve power and …

Critical Role Of Tnf-Α In Cerebral Aneurysm Formation And Progression To Rupture., Robert M Starke, Nohra Chalouhi, Md, Pascal Jabbour Md, Stavropoula Tjoumakaris, L. Fernando Gonzalez, Robert H. Rosenwasswer Md, Kosuke Wada, Kenji Shimada, David M Hasan, Nigel H Greig, Gary K Owens, Aaron Dumont

Department of Neurosurgery Faculty Papers

BACKGROUND: Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established.

METHODS: Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6'dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining.

RESULTS: …

The End Of Alzheimer's Disease - From Biochemical Pharmacology To Ecopsychosociology: A Personal Perspective, Peter J. Whitehouse

Faculty Scholarship

The future of the Alzheimer's disease (AD) field involves a more complete understanding not only the state of current scientific approaches, but also the linguistic and cultural context of preclinical and clinical research and policy activities. The challenges surrounding dementia are large and growing but are only part of broader social and health concerns. In this latter context, the current state of research in the AD area is reviewed together with necessary priorities in moving forward. Creating a more optimistic future will depend less on genetic and reductionist approaches and more on environmental and intergenerative approaches that will aid in …

Activation Of Hindbrain Neurons Is Mediated By Portal-Mesenteric Vein Glucosensors During Slow-Onset Hypoglycemia, Maryann Bohland, Aleksey Matveyenko, Maziyar Saberi, Arshad Khan, Alan Watts, Casey Donovan

Selected Works Temporary Series

Hypoglycemic detection at the portal-mesenteric vein (PMV) appears mediated by spinal afferents and is critical for the counter-regulatory response (CRR) to slow-onset, but not rapid-onset, hypoglycemia. Since rapid-onset hypoglycemia induces Fos protein expression in discrete brain regions, we hypothesized that denervation of the PMV or lesioning spinal afferents would suppress Fos expression in the dorsal medulla during slow-onset hypoglycemia, revealing a central nervous system reliance on PMV glucosensors. Rats undergoing PMV deafferentation via capsaicin, celiac-superior mesenteric ganglionectomy (CSMG), or total subdiaphragmatic vagotomy (TSV) were exposed to hyperinsulinemic–hypoglycemic clamps where glycemia was lowered slowly over 60–75 min. In response to hypoglycemia, …

Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels Do, Katie Mastoris Do, Mark Knouse Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Lymphoma Masquerading As Pneumonia With Acute Renal Failure: A Rare Clinical And Radiological Presentation Of Diffuse Large B Cell Gastric Lymphoma (Dlbcl), Ranjit R. Nair Md, Cheryl A. Bloomfield Md, Sharif A. Ali Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Proceedings - Wright State University Boonshoft School Of Medicine Sixth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Sixth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 10, 2014.

Pathobiological Implications Of Mucin (Muc) Expression In The Outcome Of Small Bowel Cancer., Hiroaki Shibahara, Michiyo Higashi, Chihaya Koriyama, Seiya Yokoyama, Iwao Kitazono, Yasuhiro Kurumiya, Michihiko Narita, Shingo Kuze, Takanori Kyokane, Saburo Mita, Toshiyuki Arai, Takehito Kato, Norihiro Yuasa, Ryuzo Yamaguchi, Hitoshi Kubota, Hideaki Suzuki, Satoshi Baba, Karine Rousseau, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and …

Photobiostimulation In C. Elegans As A Model For Low Level Light Therapy, Michael J. Spoto, Daryl D. Hurd

Science Scholars

Low-Level Laser Therapy (LLLT) is a developing therapeutic technique that has been gaining recognition in the scientific community in recent years. Previous experiments performed in LLLT research projects have been primarily mammalian and cell culture based. These experiments have produced results showing accelerated tissue repair. In this experiment, we introduce a new model, Caenorhabitidis elegans, a free-living soil nematode, to be used in LLLT research by testing the effects of exposure of the organism to various wavelengths and intensities of light commonly used in LLLT. C. elegans was shown to respond to photobiostimulation when exposed to specific wavelengths of …

Photodynamic Cancer Therapy A Study Of The Photolysis Reaction Between Porphyrin And 9,10-Diphenylanthracene, James Z. Akins

Honors College Theses

Photodynamic therapy (PDT) is a method of combating cancerous tumors. PDT works when certain molecules called photosensitizers absorb light and transfer that energy to dissolved oxygen in solution. Next, this singlet oxygen will interfere with nearby molecules that are necessary for cancer cells to function. This research focuses on the kinetics (rates) of the reaction with respect to the photosensitizer, light, and the target molecule. A laser set at 514nm was used in photolysis with the photosensitizer 5,10,15,20-Tetrakis(2,3,5,6-tetrafluorophenyl)porphyrin (TPP). To mimic cancer cells and monitor the effectiveness of the chosen photosensitizer, 9,10-Diphenylanthracene (DPA) was used as the target molecule. In …

Diagnosis Of Pancreatic Neoplasms Using A Novel Method Of Dna Methylation Analysis Of Mucin Expression In Pancreatic Juice., Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi, Yuko Goto, Taro Hara, Dai Ikebe, Taketo Yamaguchi, Yoshifumi Arisaka, Toru Niihara, Hiroto Nishimata, Sadao Tanaka, Kyoichi Takaori, Surinder K. Batra, Suguru Yonezawa

Journal Articles: Biochemistry & Molecular Biology

Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. …

Neuroplasticity And Mindfulness Meditation, Richard Widdett

Honors Theses

My thesis topic of choice was how mindfulness meditation is linked to neuroplasticity in the brain. The brain is an incredibly complex and powerful organ. Each area of the brain serves a specific purpose and is interconnected. Neuroplasticity is the term used to describe the molding and shaping of the brain based on our experiences from the moment we are born. Mindfulness is defined as the “ability to pay total attention to the present moment with a nonjudgmental awareness of the inner and/or outer experiences.” Many studies have been conducted researching the brain and meditation. The findings from these studies …

The Role Of P2x Receptors In Hiv And Opiate-Related Neurotoxicity, Mary Sorrell

Theses and Dissertations

Emerging evidence suggests that opioid drugs can exacerbate neuroAIDS. Microglia are the principal neuroimmune effectors thought to be responsible for neuron damage in HIV-infected individuals, and evidence suggests that drugs acting via opioid receptors in microglia aggravate the neuropathophysiological effects of HIV. The P2X family of ATP activated ligand-gated ion channels regulates key aspects of microglial function. In addition, opioid-dependent microglial activation has been reported to be mediated through P2X4 signaling, prompting us to investigate P2X receptors contribution to the neurotoxic effects of HIV and morphine. In vitro experiments showed treatment with TNP-ATP prevented the neurotoxic effects of morphine and/or …

Effector-Independent Motor Sequence Representations Exist In Extrinsic And Intrinsic Reference Frames., Tobias Wiestler, Sheena Waters-Metenier, Jörn Diedrichsen

Brain and Mind Institute Researchers' Publications

Many daily activities rely on the ability to produce meaningful sequences of movements. Motor sequences can be learned in an effector-specific fashion (such that benefits of training are restricted to the trained hand) or an effector-independent manner (meaning that learning also facilitates performance with the untrained hand). Effector-independent knowledge can be represented in extrinsic/world-centered or in intrinsic/body-centered coordinates. Here, we used functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis to determine the distribution of intrinsic and extrinsic finger sequence representations across the human neocortex. Participants practiced four sequences with one hand for 4 d, and then performed these sequences …

Trail-R1 Is A Negative Regulator Of Pro-Inflammatory Responses And Modulates Long-Term Sequelae Resulting From Chlamydia Trachomatis Infections In Humans, Mufadhal Al-Kuhlani, James Rothchild, Sukumar Pal, Luis M. De La Maza, Sander Ouberg, Servaas A. Morré, Deborah Dean, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

The immune system eliminates Chlamydia trachomatis infection through inflammation. However, uncontrolled inflammation can enhance pathology. In mice, TNF-related apoptosis-inducing ligand receptor (TRAIL-R), known for its effects on apoptosis, also regulates inflammation. In humans, the four homologues of TRAIL-R had never been investigated for effects on inflammation. Here, we examined whether TRAIL-R regulates inflammation during chlamydial infection. We examined TRAIL-R1 single nucleotide polymorphisms (SNPs) in an Ecuadorian cohort with and without C. trachomatis infections. There was a highly significant association for the TRAIL+626 homozygous mutant GG for infection vs no infection in this population. To confirm the results observed in the …

Pillow Talk: The Epigenetic And Physiological Effects Of Sleep Deprivation, Jennifer D. Cotter

Thinking Matters Symposium Archive

Circadian rhythms, or the 24-hour biological cycles of living cells, function as the body’s internal clock. Although circadian rhythms and sleep are very different processes, they are closely related to one another as these cycles play an important role in sleeping and waking patterns. Recent studies have shown that lack of sleep or sleep of poor quality can disrupt circadian rhythms and may actually cause cognitive disorders and memory loss, facilitate false memory production, and even alter gene expression in humans. This literature review is focused on identifying the epigenetic and physiological effects of disruptions and desynchronization in circadian rhythms …

How Spinocerebellar Ataxia Affects The Body And The Family, Anthony Simpson

Thinking Matters Symposium Archive

This poster project is a literature review that examines the causes, effects, and research being done to treat and prevent some forms of Ataxia. Ataxia is a disorder of the nervous system that causes tremors, and problems with walking, balance, memory, and mood disorders. There are many forms of Ataxia, all affecting various genes, but all have the devastating effect of the loss of the ability to move around without aid. Mental ability is not affected, yet the patient loses the ability to control their body. Most forms are caused by genetic mutations. For example, Fragile X associated tremor/ataxia syndrome …

Glutamate Transporter Control Of Ambient Glutamate Levels, Weinan Sun, Denis M. Shchepakin, Leonid Kalachev, Michael P. Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

Accurate knowledge of the ambient extracellular glutamate concentration in brain is required for understanding its potential impacts on tonic and phasic receptor signaling. Estimates of ambient glutamate based on microdialysis measurements are generally in the range of ∼2–10 μM, approximately 100-fold higher than estimates based on electrophysiological measurements of tonic NMDA receptor activity (∼25–90 nM). The latter estimates are closer to the low nanomolar estimated thermodynamic limit of glutamate transporters. The reasons for this discrepancy are not known, but it has been suggested that microdialysis measurements could overestimate ambient extracellular glutamate because of reduced glutamate transporter activity in a …

Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, Diana Savoly

Graduate School of Biomedical Sciences Theses and Dissertations

Protein Phosphatase 2A (PP2A) is a tumor suppressor involved in the regulation of several signaling pathways and the cell cycle. PP2A becomes inactivated by several inhibitors, including Cancerous Inhibitor of PP2A (CIP2A). CIP2A has been identified as an oncogene, which is over-expressed in cancers and inhibits PP2A through direct interaction. CIP2A is recognized as a biomarker for cancer; however, it is not cancer-specific. Therefore, we identified and examined the use of CIP2A-regulated proteins as potential biomarkers in prostate cancer to better diagnose prostate cancer in patients. Currently, Prostate Specific Antigen (PSA) is widely used to detect prostate cancer; however, it …

Bcl2 Expression And Bcl2/Myc Dual Expression Predicts Inferior Survival In Primary Central Nervous System Lymphoma, Guldeep Uppal, Md, Zi-Xuan (Zoe) Wang, Phd, Renu Bajaj, Phd, Mark T. Curtis, Md, Phd, Charalambos C. Solomides, Md, Jon Glass, Md, Peter M. Banks, Stephen C. Peiper, Md, Jerald Z. Gong, Md

Department of Pathology, Anatomy, and Cell Biology Resident's Posters

Background

Primary CNS lymphoma (PCNSL) is a rare type of diffuse large B-cell lymphoma (DLBCL) arising from and usually confined to CNS. Understating of the pathogenesis and prognostic markers is a challenge due to rarity of this neoplasm and paucity of the material available to study. Recent studies have shown that dual expression of MYC and BCL2 in DLBCL contributes to inferior overall survival. The prognostic value of MYC and BCL2 in PCNSL is not well studied.

Evidence For Aberrant Astrocyte Hemichannel Activity In Juvenile Neuronal Ceroid Lipofuscinosis (Jncl)., Maria Burkovetskaya, Nikolay Karpuk, Juan Xiong, Megan Bosch, Michael D. Boska, Hideyuki Takeuchi, Akio Suzumura, Tammy Kielian

Journal Articles: Pathology and Microbiology

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have …

Bisphenol A Exposure And Cardiac Electrical Conduction In Excised Rat Hearts, Nikki G. Posnack, Rafael Jaimes Iii, Huda Asfour, Luther Swift, Anastasia M. Wengrowski, Narine Sarvazyan, Matthew Kay

Pharmacology and Physiology Faculty Publications

BACKGROUND:

Bisphenol A (BPA) is used to produce polycarbonate plastics and epoxy resins that are widely used in everyday products, such as food and beverage containers, toys and medical devices. Human biomonitoring studies have suggested that a large proportion of the population may be exposed to BPA. Recent epidemiological studies have reported correlations between increased BPA urinary concentrations and cardiovascular disease; yet the direct effects of BPA on the heart are unknown.

OBJECTIVES:

The goal of our studies was to measure BPA's effect (0.1-100 μM) on cardiac impulse propagation ex vivo, using excised whole hearts from adult rats.

METHODS: …