Digital Commons Network^™

Immobilizing Mutation In An Unconventional Myosin15a Affects Not Only The Structure Of Mechanosensory Stereocilia In The Inner Ear Hair Cells But Also Their Ionic Conductances, Diana Syam

Theses and Dissertations--Medical Sciences

In the inner and outer hair cells (OHCs) of the inner ear, an unconventional myosin 15a localizes at the tips of mechanosensory stereocilia and plays an important role in forming and maintaining their normal structure. A missense mutation makes the motor domain of myosin 15a dysfunctional and is responsible for the congenital deafness DFNB3 in humans and deafness and vestibular defects in Shaker-2 (Sh2) mouse model. All hair cells of homozygous Shaker-2 mice (Myo15^sh2/sh2) have abnormally short stereocilia, but, only stereocilia of Myo15^sh2/sh2OHCs start to degenerate after the first few days of postnatal development …

Phosphatidylinositol 3-Kinase (Pi3k) As A Therapeutic Target In Nsclc, Christopher W. Stamatkin

Theses and Dissertations--Pharmacy

Deregulated activation of phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies. The functions of this pathway are critical for normal cell metabolism, proliferation, and survival. In lung cancers, the PI3K pathway activity is often aberrantly driven by multiple mutations, including EGFR, KRAS, and PIK3CA. Molecules targeting the PI3K pathway are intensely investigated as potential anti-cancer agents. Although inhibitors of the pathway are currently in clinical trials, rational and targeted use of these compounds, alone or in combination, requires an understanding of isoform-specific activity in context. We sought to identify class IA PI3K enzyme (p110a/PIK3CA, p110b/PIK3CB, p110d/PIK3CD) activities using …

Expression And Splicing Of Alzheimer’S Disease Risk Gene Phosphatidylinositol-Binding Clathrin Assembly Protein, Ishita Parikh

Theses and Dissertations--Physiology

Recent Genome Wide Association Studies (GWAS) have identified a series of single nucleotide polymorphism (SNP)s that are associated with Alzheimer’s disease (AD). One of the SNPs, rs3851179 (G/A), is near the gene phosphatidylinositol-binding clathrin assembly protein (PICALM). To evaluate whether this SNP is associated with PICALM expression, we quantified PICALM mRNA in 56 brain cDNA samples. Using linear regression analysis, we analyzed PICALM expression relative to rs3851179, AD status, and cell type specific markers. An association was detected between rs3851179 and PICALM, microvessel mRNA, glial fibrillary acidic protein (GFAP) mRNA, and synaptophysin (SYN) mRNA. To gain clarity …

Anti-Müllerian Hormone In Stallions And Mares: Physiological Variations, Clinical Applications, And Molecular Aspects, Anthony N.J. Claes

Theses and Dissertations--Veterinary Science

Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein that is best known for its role in regression of the Müllerian duct in the male fetus. Accumulating evidence indicates that AMH also has an important role during different physiological processes after birth. In contrast to other species, relatively little is known about AMH in the horse. In chapter one, developmental and seasonal changes in serum AMH concentrations in male horses were determined, and the use of AMH for determination of retained cryptorchid testes was established. In chapter two, the interrelationship between plasma AMH concentrations, antral follicle counts (AFC), and age in mares …

Science Classics, Mark Masthay

Chemistry Faculty Publications

An essay on the impact of the works in the Imprints and Impressions: Milestones in Human Progress, an exhibition of rare books from the collection of Stuart Rose. Exhibition was held Sept. 29-Nov. 9, 2014, at the University of Dayton.

Chemopreventive Effects Of Pterostilbene In Metastatic Prostate Cancer Cells, Phillip A. Zook

PCOM Biomedical Studies Student Scholarship

Recent studies find that pterostilbene (PTS) exhibits more favorable drug properties and similar chemopreventive effects to its structural analogue resveratrol (RSV). However, few studies describe the activity of PTS in prostate cancer (PCa). Here, we conducted cell count experiments to assess the effects of PTS on metastatic PCa cell viability and to compare the potency of PTS to RSV in this respect. We also performed experiments to assess the effects of PTS on the androgen receptor (AR) and AR-mediated events. We used qPCR to measure the mRNA levels of the androgenresponsive gene (ARG), prostate-specific antigen (PSA), and Western blots to …

An Analysis Of Abnormal Electrocardiograms In First And Second Year Medical School Students, Molly Anne Kalish

PCOM Biomedical Studies Student Scholarship

The high stress level placed upon medical school students, particularly during their first and second didactic years, may have a negative effect on their health. Although surveys and subjective questionnaires have been used to evaluate the effects medical school has upon a student’s cardiovascular health, there has been little clinical data obtained to confirm this notion. The aim of this longitudinal study was to demonstrate whether any abnormal cardiovascular parameters, specifically QTc wave interval, cardiac axis vector and blood pressure abnormalities, could be documented to occur in two different classes of medical students during their first two years. Such information …

Effect Of Heme Oxygenase-1 On Matrix Metalloproteinase-3 Expression In Human Fibroblasts, Theresa A. Stangl

PCOM Biomedical Studies Student Scholarship

Heme oxygenase-1(HO-1) is an enzyme that plays a very important role in the resolution of inflammation. HO-1-based therapies are effective in a number of disease conditions. However, HO-1 also increases tumor growth, angiogenesis, metastasis and chemoresistance. Matrix metalloproteinase-3 (MMP-3) is an enzyme involved in physiological and pathophysiological tissue remodeling. Unbalanced expression of MMPs is a key feature of connective tissue destruction in chronic inflammatory conditions. Previously shown in this laboratory, the HO-1 inducer, hemin, increased MMP-3 mRNA expression in some HGF cultures. To assess whether HO-1 and/or its products regulate expression of MMP-3 in human fibroblasts, the effect of HO-1 …

Trim68 Negatively Regulates Ifn-B Production By Degrading Trk Fused Gene, A Novel Driver Of Ifn-B Downstream Of Anti-Viral Detection Systems, Claire Wynne, Elisa Lazzari, Siobhan Smith, Eoghan Mccarthy, Joan Ni Gabhann, Lara Kallai, Rowan Higgs, Sally Ann Cryan, Christine Byron, Caroline Jefferies

Articles

In recent years members of the tripartite motif-containing (TRIM) family of E3 ubiquitin ligases have been shown to both positively and negatively regulate viral defence and as such are emerging as compelling targets for modulating the anti-viral immune response. In this study we identify TRIM68, a close homologue of TRIM21, as a novel regulator of Toll-like receptor (TLR)- and RIG-I-like receptor (RLR)-driven type I IFN production. Proteomic analysis of TRIM68-containing complexes identified TRK-fused gene (TFG) as a potential TRIM68 target. Overexpression of TRIM68 and TFG confirmed their ability to associate, with TLR3 stimulation appearing to enhance the interaction. TFG is …

Comparison Of Semi-Automated And Manual Measurements Of Carotid Intima-Media Thickening, Oscar Mac Ananey, G Mellotte, V Maher

Articles

Carotid intima-media thickening (CIMT) is a marker of both arteriosclerotic and atherosclerotic risks. Technological advances have semiautomated CIMT image acquisition and quantification. Studies comparing manual and automated methods have yielded conflicting results possibly due to plaque inclusion in measurements. Low atherosclerotic risk subjects (n = 126) were recruited to minimise the effect of focal atherosclerotic lesions on CIMT variability. CIMT was assessed by high-resolution B-mode ultrasound (Philips HDX7E, Phillips, UK) images of the common carotid artery using both manual and semiautomated methods (QLAB, Phillips, UK). Intraclass correlation coefficient (ICC) and the mean differences of paired measurements (Bland-Altman method) were used …

Detection Of Caga And Vaca Genotypes Of Helicobacter Pylori Isolates From A University Hospital In Ankara Region, Turkey, Ceren Erdoğdu, Zeynep Saribaş, Yakut Akyön Yilmaz

Turkish Journal of Medical Sciences

The cagA and vacA profiles and their association with clinical findings show a distinct geographical distribution. In the present study, we aimed to determine the cagA status and vacA allelic subtypes in strains isolated from a university hospital in Ankara and to evaluate their associations with histopathological and endoscopic findings. Materials and methods: A total of 120 H. pylori strains from stock cultures positive for the ureA gene were randomly included in the present study. Of these strains, cagA and vacA allelic subtypes (s1a, s1b, s2, m1, m2) were examined by polymerase chain reaction. Results: Of the 120 strains, 64 …

Serotonin Receptor 2-Induced Mitochondrial Biogenesis As A Therapeutic Strategy For The Treatment Of Multiple Pathologies, Jennifer Linton Harmon

MUSC Theses and Dissertations

Mitochondrial dysfunction is a common pathophysiological feature in many acute and chronic organ injury states. Often, this mitochondrial dysfunction is sub-lethal and persistent and is a major contributor to loss of cellular function in the absence of cell death. Mitochondrial biogenesis (MB) is the process by which new mitochondria are created, and studies have demonstrated that pharmacological induction of MB can reverse loss of mitochondrial content, improve mitochondrial function and reduce measures of acute organ injury. Several classes of pharmacological agents that induce MB through divergent mechanisms have been identified. Previous studies demonstrated that 2,5-Dimethoxy-4-iodoamphetamine (DOI), a potent but non-specific …

The Involvement Of The Ca2+-Independent Phospholipase A2ss In The Pathogenesis Of Type 1 Diabetes, Robert N. Bone

All ETDs from UAB

chapters test the role of non-steady moisture or temperature on sex ratios produced by the

Mitochondrial Genetics Modify Body Composition, Metabolic Efficiency And Myocardial Metabolism, Kimberly Joanne Dunham-Snary

All ETDs from UAB

Obesity and cardiometabolic pathologies have reached epidemic levels worldwide over the last 30 years. Currently, the majority of research investigating possible genetic causes of obesity is focused on nuclear DNA (nDNA). While this has lead to the development of numerous animal models, it is apparent the etiology of obesity is more complex than single gene mutations. Recently it has also been suggested that mitochondrial DNA (mtDNA) mutations sustained during evolution as a consequence of our prehistoric environment may influence individual propensity and risk of disease. Contemporary human populations are no longer faced with the challenges of our ancestors such as …

Conformational Changes And Translocation Of Tissue-Transglutaminase To The Plasma Membranes: Role In Cancer Cell Migration, Ambrish Kumar, Jianjun Hu, Holly A. Lavoie, Kenneth B. Walsh, Donald J. Dipette, Ugra S. Singh

Faculty Publications

Background

Tissue-transglutaminase (TG2), a dual function G-protein, plays key roles in cell differentiation and migration. In our previous studies we reported the mechanism of TG2-induced cell differentiation. In present study, we explored the mechanism of how TG2 may be involved in cell migration.

Methods

To study the mechanism of TG2-mediated cell migration, we used neuroblastoma cells (SH-SY5Y) which do not express TG2, neuroblastoma cells expressing exogenous TG2 (SHY_TG2), and pancreatic cancer cells which express high levels of endogenous TG2. Resveratrol, a natural compound previously shown to inhibit neuroblastoma and pancreatic cancer in the animal models, was utilized to …

Empirical Models Of Scalp-Eeg Responses Using Non-Concurrent Intracranial Responses, Komalpreet Kaur, Jerry J. Shih, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

Objective- This study presents inter-subject models of scalp-recorded electroencephalographic (sEEG) event-related potentials (ERPs) using intracranially recorded ERPs from electrocorticography and stereotactic depth electrodes in the hippocampus, generally termed as intracranial EEG (iEEG).

Approach- The participants were six patients with medically-intractable epilepsy that underwent temporary placement of intracranial electrode arrays to localize seizure foci. Participants performed one experimental session using a brain-computer interface matrix spelling paradigm controlled by sEEG prior to the iEEG electrode implantation, and one or more identical sessions controlled by iEEG after implantation. All participants were able to achieve excellent spelling accuracy using sEEG, four of the participants …

Hypothesis Testing In Normal Admixture Models To Detect Heterogeneous Genetic Signals, Qian Fan, Richard Charnigo, Zohreh Talebizadeh, Hongying Dai

Manuscripts, Articles, Book Chapters and Other Papers

In this work we consider a three-component normal mixture model in which one component is known to have mean zero and the other two contaminating components have a nonnegative and a nonpositive mean respectively, while all three components share a common unknown variance parameter. One potential application of this model may be in prioritizing statistical scores obtained in biological experiments, including genetics data. Such a mixture model may be useful in describing the distribution of numerous Z test statistics corresponding to different genes or SNPs, such that a “significant” Z test statistic for a particular gene suggests its connection to …

Transmural Heterogeneity Of Cellular Level Cardiac Contractile Properties In Aging And Heart Failure, Premi Haynes

Theses and Dissertations--Physiology

The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms.

Age …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

The Clinical Utility Of The Halosperm Assay And The Development Of A Simplified Method Of Human Semen Storage For The Testing Of Sperm Dna Fragmentation, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Male infertility is typically diagnosed upon routine semen analysis following the World Health Organisation’s (WHO) semen analysis manual. Recent editions of the manual have essentially changed the diagnosis of a semen sample, prompting debate between experts as to which edition should be followed. Deoxyribonucleic Acid (DNA) integrity analysis is proving to be a useful adjunct to semen analysis as 15% of infertile men have a normal semen analysis but they have an increased DNA fragmentation level (DFL) which has been associated with increased disease incidence in any resultant offspring. However, such tests are not endorsed by the WHO, possibly due …

The Impact Of Implementing A Sudden Infant Death Syndrome Education Package In Jordan, Shereen Hamadneh

Theses: Doctorates and Masters

Background: Sudden Infant Death Syndrome (SIDS) is a problem worldwide. In North Jordan, SIDS rate was high as 1.32 per 1,000 live births and contributed 6% to the infant mortality rate (Bataineh, Shawagfeh, & Twalbeh, 2008). However, SIDS risk factors are preventable and can be reduced by improving knowledge and changing relevant behaviours of parents and healthcare providers (American Academy of Pediatrics, 2013; American SIDS Institute, 2011; Bataineh, Hussein Shawagfeh, & Twalbeh, 2008; Bredemeyer, 2004; Grazel, Phalen, & Polomano, 2010b; Moon, Oden, & Grady, 2004; NICHD, 2010). Still educating Jordanians about SIDS has not been a national health policy priority. …

Plasma Insulin-Degrading Enzyme: Characterisation And Evaluation As A Potential Biomarker For Alzheimer's Disease, Michelle Tegg

Theses: Doctorates and Masters

Alzheimer’s disease (AD) is increasing in prevalence due to increasing lifespan and altered lifestyle. It is the fourth major cause of death in Western countries, resulting in significant economic and social impact (Von Strauss, et al., 1999; Goate, 1997). There are no blood biomarkers currently accepted for the diagnosis of AD, and the identification of suitable biomarkers would eventually reduce the necessity for invasive, expensive and slow diagnostic procedures, as well as facilitate prognostic studies. An AD blood test would decrease the need for delaying diagnosis due to ambivalent presentation, and allow therapeutic intervention to commence at an earlier …

Vitamin C As An Antioxidant: Evaluation Of Its Role On Pulmonary Contusion Experimental Model, Rana Sirmali, Zeynep Gi̇ni̇ş, Mehmet Sirmali, Okan Solak, Bengü Şeli̇man, Yetki̇n Ağaçkiran, Namik Deli̇baş

Turkish Journal of Medical Sciences

To analyze the protective activity of vitamin C on the lungs by assessing biochemical and histopathological analysis after performing an experimental isolated lung contusion model. Materials and methods: Fifty-four male Sprague-Dawley male rats were used. The rats were randomly separated into 4 groups. Vitamin C (200 mg/kg) was injected intraperitoneally 30 min after trauma. Blood samples were obtained for myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities and malondialdehyde (MDA) levels. Blood gas analysis and bronchoalveolar lavage was performed. The lung tissue was also extracted for histopathological examination. Results: The lung contusion enhanced MDA, SOD, CAT, …

Effect Of Nodule Size On The Reliability Of Fine-Needle Aspiration Biopsy In Thyroid Nodules, Ali̇ Erkan Uçar, Seyyi̇t Muhsi̇n Sarikaya, Ömer Parlak, Abdussamed Yalçin

Turkish Journal of Medical Sciences

To investigate the reliability of fine-needle aspiration biopsy (FNAB) in thyroid nodules and benign/malignant discrimination, particularly in large nodules. Materials and methods: A retrospective analysis of 1466 nodules in 402 patients with thyroid nodules who underwent thyroid surgery was made. The pathologic results of the thyroid nodules from preoperative FNAB and postoperative surgical pathology results were compared. Results: FNAB was found to be in accordance with the postoperative pathologic results. A concordance between the FNAB and postoperative pathologic results, particularly in nodules less than 3 cm in size, was detected. However, a similar finding was not detected in nodules larger …

Detection The Frequency Of Per-1 Type Extended-Spectrum Ss-Lactamase-Producing Acinetobacter Baumannii Clinical Isolates In Turkey: A Multicenter Study, Gülşah Aşik, Mehmet Özdemi̇r, Muhammet Güzel Kurtoğlu, Server Yağci, Lütfi̇ye Öksüz, Mustafa Gül, Mücahi̇de Esra Koçoğlu, Emel Sesli̇ Çeti̇n, Adnan Seyrek, Mustafa Berktaş, Ahmet Ayyildiz, İhsan Hakki Çi̇ftci̇

Turkish Journal of Medical Sciences

\beta-Lactamases are an important resistance mechanism in Acinetobacter baumannii. Pseudomonas extended-resistance (PER-1) type \beta-lactamase-producing strains have been reported from various geographic locations; however, PER-1 type \beta-lactamases from Turkish hospitals have not been investigated extensively. The aim of this study was to determine the prevalence of PER-1 type \beta-lactamases in A. baumannii isolates in various regions of Turkey. Materials and methods: A total of 763 clinical A. baumannii isolates were collected from 9 university hospitals and 2 state hospitals between 2008 and 2011. Molecular amplification of the OXA-51 gene from the A. baumannii genome was performed in order to verify identification …

Folate And Homocysteine Metabolisms And Their Roles In The Biochemical Basis Of Neuropsychiatry, Alpaslan Coşar, Osman Meti̇n İpci̇oğlu, Ömer Özcan, Mustafa Gültepe

Turkish Journal of Medical Sciences

The term 'one-carbon metabolism' is commonly used to describe 3 separate metabolic processes: folate metabolism, the homocysteine remethylation cycle, and the transsulfuration pathway. Folate metabolism concerns the biochemical reactions in which endogenous and exogenous one-carbon units are transferred to tetrahydrofolates. The remethylation cycle is used for the synthesis of methionine from homocysteine with one-carbon units that come from folate. This methionine is then used for the synthesis of S-adenosyl methionine, which is a general donor of methyl groups for many biochemical reactions in the human body. In the transsulfuration pathway, some amino acids and polypeptides, such as cystathionine, cysteine, and …

Indoor Air Quality In Primary Schools In Keçiören, Ankara, Mustafa Alparslan Babayi̇ği̇t, Bi̇lal Bakir, Ömer Faruk Tekbaş, Recai̇ Oğur, Abdullah Kiliç, Serdar Ulus

Turkish Journal of Medical Sciences

To increase the awareness of environmental risk factors by determining the indoor air quality status of primary schools. Materials and methods: Indoor air quality parameters in 172 classrooms of 31 primary schools in Keçiören, Ankara, were examined for the purpose of assessing the levels of air pollutants (CO, CO_2, SO_2, NO_2, and formaldehyde) within primary schools. Results: Schools near heavy traffic had a statistically significant mean average of CO and SO_2 (P < 0.05). The classrooms that had more than 35 students had higher and statistically significant averages of CO_2, SO_2, NO_2, and formaldehyde compared to classrooms that had fewer than 35 students (P < 0.05). Of all classrooms, 29% had 100 CFU/100 mL and higher concentrations of microorganisms, which were not pathogens. Conclusion: Indoor air quality management should continually be maintained in primary schools for the prevention and control of acute and chronic diseases, particularly considering biological and chemical pollution.

Evaluating The Clinical And Physiological Effects Of Long Term Ultraviolet B Radiation On Guinea Pigs (Cavia Porcellus), Megan K. Watson, Adam W. Stern, Amber L. Labelle, Stephen Joslyn, Timonthy M. Fan, Katie Leister, Micah Kohles, Kemba Marshall, Mark A. Mitchell

School of Veterinary and Biomedical Sciences: Faculty Publications

Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B …

Bmp-2 Overexpression Augments Vascular Smooth Muscle Cell Motility By Upregulating Myosin Va Via Erk Signaling, Ming Zhang, Min Yang, Liping Liu, Wayne Bond Lau, Hai Gao, Mankun Xin, Lixiao Su, Jian Wang, Shujuan Cheng, Qian Fan, Jinghua Liu

Department of Emergency Medicine Faculty Papers

Background. The disruption of physiologic vascular smooth muscle cell (VSMC) migration initiates atherosclerosis development. The biochemical mechanisms leading to dysfunctional VSMC motility remain unknown. Recently, cytokine BMP-2 has been implicated in various vascular physiologic and pathologic processes. However, whether BMP-2 has any effect upon VSMC motility, or by what manner, has never been investigated. Methods. VSMCs were adenovirally transfected to genetically overexpress BMP-2. VSMC motility was detected by modified Boyden chamber assay, confocal time-lapse video assay, and a colony wounding assay. Gene chip array and RT-PCR were employed to identify genes potentially regulated by BMP-2. Western blot and real-time PCR …

Multifunctional Gold Nanocarriers For Cancer Theranostics - From Bench To Bedside And Back Again?, Joao Conde, Furong Tian, Pedro V. Baptista, Jesús M. De La Fuente

Books / book chapters

No abstract provided.