Digital Commons Network^™

Investigations Of Interleukin-1 Alpha As A Novel Stroke Therapy In Experimental Ischemic Stroke, Kathleen Elizabeth Salmeron

Theses and Dissertations--Neuroscience

Stroke is a leading cause of death and disability worldwide. Although rapid recognition and prompt treatment have dropped mortality rates, most stroke survivors are left with permanent disability. Approximately 87% of all strokes result from the thromboembolic occlusion of the cerebrovasculature (ischemic strokes). Potential stroke therapeutics have included anti-inflammatory drugs, as well as many other targets with the goal of mitigating the acute and chronic inflammatory responses typically seen in an ischemic stroke. While these approaches have had great success in preclinical studies, their clinical translation has been less successful. Master inflammatory cytokines, such as IL-1, are of particular interest. …

Myosin-Xva Is Key Molecule In Establishing The Architecture Of Mechanosensory Stereocilia Bundles Of The Inner Ear Hair Cells, Shadan Hadi

Theses and Dissertations--Medical Sciences

Development of hair cell stereocilia bundles involves three stages: elongation, thickening, and supernumerary stereocilia retraction. Although Myo-XVa is known to be essential for stereocilia elongation, its role in retraction/thickening remains unknown. We quantified stereocilia numbers/diameters in shaker-2 mice (Myo15^sh2) that have deficiencies in “long” and “short” isoforms of myosin-XVa, and in mice lacking only the “long” myosin-XVa isoform (Myo15^ΔN). Our data showed that myosin-XVa is largely not involved in the developmental retraction of supernumerary stereocilia. In normal development, the diameters of the first (tallest)/second row stereocilia within a bundle are equal and grow simultaneously. …

The Prebiotic Inulin Beneficially Modulates The Gut-Brain Axis By Enhancing Metabolism In An Apoe4 Mouse Model, Jared D. Hoffman

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia and a growing disease burden that has seen pharmacological interventions primarily fail. Instead, it has been suggested that preventative measures such as a healthy diet may be the best way in preventing AD. Prebiotics are one such potential measure and are fermented into metabolites by the gut microbiota and acting as gut-brain axis components, beneficially impact the brain. However, the impact of prebiotics in AD prevention is unknown. Here we show that the prebiotic inulin increased multiple gut-brain axis components such as scyllo-inositol and short chain fatty acids in the …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Under The Influence: An Interdisciplinary Approach To Psychedelics, Jody Roun

Master of Liberal Studies Theses

The following research will outline the effects of psychedelics from an interdisciplinary approach, which is to say that I will explore the neuroscience behind psychedelic drugs and how it relates to creativity, as a primary focus, while examining the role of additional points included along the way. The goal of this research, is to gain a deeper understanding of psychedelics and truly decipher what it means to be under the influence, as the most important goal of this human existence is to achieve understanding. The aforementioned is a point that great minds like Albert Einstein and Humphry Osmond impressed on …

Effect Of Hemiepiphysiodesis On The Growth Plate: The Histopathological Changes And Mechanism Exploration Of Recurrence In Mini Pig Model., Jing Ding, Jin He, Zhi-Qiang Zhang, Zhen-Kai Wu, Fang-Chun Jin

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure.

Methods: Eight 3-month-old male Bama miniature pigs sustained surgeries on the …

Novel Mediators Of The Blood Pressure Response To Acute Psychosocial Stress In Health And Disease, Brandon Fox

All ETDs from UAB

Psychosocial stress occurs in response to threatening or uncertainty-provoking stimuli and triggers a complex physiological reaction that facilitates survival and adaptation. In the cardiovascular system, acute psychosocial stress elicits a rapid increase in blood pressure, and importantly, cumulative exposure to psychosocial stress is a risk factor for cardiovascular disease. The present studies examined the impact of psychosocial stress on the cardiovascular system in both health and disease. Circulating endothelin-1 (ET-1) levels are induced by psychosocial stress. We hypothesized that endothelium-derived ET-1 contributes to the pressor response to stress via activation of the endothelin A (ETA) receptor. Vascular endothelium-specific ET-1 knockout …

The Perspectives Of Men In Mexico City About Vasectomy, Isabel Vieitez Martínez, Adriana Ramos

Reproductive Health

As part of World Vasectomy Day, the Population Council Mexico conducted an exploratory study about the reasons and concerns that led men to seek a no-scalpel vasectomy (NSV) during the 24-hour “Vasectomy-athon” in Mexico City in 2017. This study was intended as the first part of a longer cohort study that would follow up with the men, and their partners, to learn about their experiences with the procedure and its effects, if any, on their relationships. Based on the findings, the report recommends that the Mexican Ministry of Health (SSA) continue integrating NSV information, counseling, and services within the National …

The Perspectives Of Men In Mexico City About Vasectomy—Brief, Isabel Vieitez Martínez, Adriana Ramos

Reproductive Health

On November 17, 2017, Mexico City took part in the global World Vasectomy Day campaign promoting men’s participation in family planning, especially through no-scalpel vasectomy (NSV). During the event the Population Council Mexico conducted an exploratory study to better understand the reasons men chose NSV, as well as their concerns before and after the procedure. The study found that the principal reason for seeking NSV among men surveyed was their achievement of a desired family size, for themselves and their partners. The study further reveals the need to disseminate information through mass media, social networks, and all levels of the …

The Effect Of Obstructive Sleep Apnea Syndrome On The Central Auditory System, Ayşe İri̇z, Mehmet Düzlü, Oğuz Köktürk, Yusuf Kemal Kemaloğlu, Faki̇h Ci̇hat Eravci, Işik Si̇bel Küçükünal, Recep Karamert

Turkish Journal of Medical Sciences

Background/aim: Obstructive sleep apnea syndrome (OSAS) is a disease characterized by repeated hypoxia attacks during sleep. The effect of hypoxia on the central nervous system is a well-known entity. In this study we aimed to investigate the effect of OSAS on the central auditory system. Materials and methods: Twenty-one OSAS patients diagnosed by polysomnography (PSG) and 10 control subjects were included in the study. After a thorough otorhinolaryngology examination, all subjects underwent pure tone audiometry (250 to 8000 Hz frequency). The subjects with normal otoscopic examination and hearing threshold were included in the study. All participants underwent speech discrimination analyses …

Effects Of Di Erent Drug Treatments On The Proliferation Of Human Ovarian Carcinoma Cell Line Mdah-2774, Şule Ayla, Ayhan Bi̇li̇r, Ahmet Şenol Ertürkoğlu, Gamze Tanriverdi̇, Burak Cem Soner, Kenan Sofuoğlu, Laura Ghisolfi, Gülperi̇ Öktem

Turkish Journal of Medical Sciences

Background/aim: In this study, the e ects of resveratrol as a natural polyphenol compound, gemcitabine as an antimetabolite that has nucleoside structure analogous to deoxycytidine, and para-aminophenol-derived paracetamol were investigated with single and combined applications in monolayers of the MDAH-2774 human ovarian cancer cell line. Materials and methods: Drugs were evaluated in cell culture with respect to cell proliferation, cell cytotoxicity (trypan blue dye exclusion test), synthesis phase of cell cycle, and cell structure in 24, 48, 72, and 96 h. Result: Resveratrol and gemcitabine diminished both cell proliferation and cell cycle synthesis phase indication in monolayer cell cultures (P < 0.05). All combination groups showed similar e ects that were mainly more e ective in respect to single usage of resveratrol and gemcitabine in monolayer cell cultures. Conclusion: The effects of gemcitabine, resveratrol, and paracetamol were investigated in monolayers of the MDAH-2774 human ovarian cancer cell line and a decrease in cell number in cell cycle synthesis phase, prevention of cell proliferation, and destruction of cell structure were observed.

Visfatin Levels In Hormonally Inactive Adrenal Adenoma And Their Association Withmetabolic Parameters, Alp Atasoy, Evri̇m Çakir, Süleyman Ahbab, Yasemi̇n Erdoğan Döventaş, Maci̇t Koldaş, Hayri̇ye Esra Ataoğlu, Mustafa Yeni̇gün

Turkish Journal of Medical Sciences

Background/aim: In parallel with increased frequency and higher quality of imaging techniques, the prevalence of adrenal adenoma has gradually increased. However, despite the growing incidence, the metabolic and tumorigenesis processes involved in its etiology are still unclear. Although visfatin has been reported to be associated with inflammation and tumorigenesis, its role in adrenal adenoma has not yet been investigated. Therefore, the present study was performed with an aim to evaluate visfatin levels and cardiometabolic risk factors in patients with adrenal adenoma. Materials and methods: Thirty patients recently diagnosed with adrenal adenoma along with 30 healthy participants were studied in a …

Evaluation Of The Performance Of Maldi-Tof Ms And Dna Sequence Analysis In The Identification Of Mycobacteria Species, Işin Akyar, Cengi̇z Çavuşoğlu, Meltem Ayaş, Süheyla Sürücüoğlu, Zeynep Arzu İlki̇, Deni̇z Ece Kaya, Yeşi̇m Beşli̇

Turkish Journal of Medical Sciences

Background/aim: Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry is an alternative way of identifying mycobacteria via the analysis of biomolecules. It is being increasingly used in routine microbiology practice since it permits early, rapid, and cost-effective identification of pathogens of clinical importance. In this study, we aimed to evaluate the efficacy of phenotypic identification of mycobacteria by the MALDI-TOF MS MBT Mycobacteria Library (ML) 4.0 (Bruker, Daltonics) compared to standard sequence analysis. Materials and methods: A total of 155 Mycobacterium clinical and external quality control isolates, comprising nontuberculous mycobacteria (NTM) (n = 95) and the Mycobacterium tuberculosis complex (MTC) (n …

Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni

Bioelectrics Publications

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs …

Corrigendum: Identification Of The Cftr C.1666a > G Mutation In Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis, Yan Lu, Yu-Wei Da, Yong-Biao Zhang, Xin-Gang Li, Min Wang, Li Di, Mi Pang, Lin Lei

Research outputs 2014 to 2021

A Corrigendum on Identification of the CFTR c.1666A>G Mutation in Hereditary Inclusion Body Myopathy Using Next-Generation Sequencing Analysis

by Lu, Y., Da, Y.-W., Zhang, Y.-B., Li, X.-G., Wang, M., Di, L., et al. (2018). Front. Neurosci. 12:329. doi: 10.3389/fnins.2018.00329

An error was found in the first and second sentence of the original article's abstract.

The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome

Wayne State University Dissertations

The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …

Characterization Of Cdk(5) Inhibitor, 20-223 (Aka Cp668863) For Colorectal Cancer Therapy, Caroline M. Robb, Smit Kour, Jacob I. Contreras, Ekta Agarwal, Carter J. Barger, Sandeep Rana, Yogesh Sonawane, Beth K. Neilsen, Margaret Taylor, Smitha Kizhake, Rhishikesh N. Thakare, Sanjib Chowdhury, Jing Wang, Jennifer D. Black, Michael A. Hollingsworth, Michael G. Brattain, Amarnath Natarajan

Journal Articles: Biochemistry & Molecular Biology

Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers. Our lab synthesized and characterized CP668863 – now called 20-223. In our established colorectal cancer xenograft model, 20-223 reduced …

Pancreatic Cancer Associated With Obesity And Diabetes: An Alternative Approach For Its Targeting, Ramesh Pothuraju, Satyanarayana Rachagani, Wade M. Junker, Sanjib Chaudhary, Saraswathi Viswanathan, Sukhwinder Kaur, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Pancreatic cancer (PC) is among foremost causes of cancer related deaths worldwide due to generic symptoms, lack of effective screening strategies and resistance to chemo- and radiotherapies. The risk factors associated with PC include several metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (T2DM). Studies have shown that obesity and T2DM are associated with PC pathogenesis; however, their role in PC initiation and development remains obscure.

MAIN BODY: Several biochemical and physiological factors associated with obesity and/or T2DM including adipokines, inflammatory mediators, and altered microbiome are involved in PC progression and metastasis albeit by different …

Optimisation Of Ion Exchange Chromatography Purification Protocols For A Staphylococcal Peptidoglycan Degrading Hydrolase Enzyme, Fiona Maher

Theses

Bacteriophage (phage) are the most abundant biological entities on earth and were first discovered by d’Herelle in 1917. They are found wherever their hosts live and, like all viruses they do not have the ability to make their own protein. Therefore, in order to reproduce, phage must invade and infect bacterial cells. This project focused on the optimisation of Ion Exchange Chromatography purification protocols for a staphylococcal peptidoglycan degrading hydrolase enzyme (CHAPk). The project objective was to obtain the greatest yield of enzyme from the growth of the E.coU XL 1-Blue expression system into which the vector pQE60 was previously …

Takayasu Arteritis: An Update, Gökhan Keser, Kenan Aksu, Rafi̇ Haner Di̇reskeneli̇

Turkish Journal of Medical Sciences

Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel systemic vasculitis, mostly due to difficulties in early diagnosis and assessing actual disease activity. Since there are no specific diagnostic laboratory tests, biomarkers, or autoantibodies, many patients experience considerable delay in diagnosis. Remembering the possibility of TAK together with the use of acute phase responses and appropriate imaging studies may be helpful for early diagnosis. Since there may be discrepancies between systemic and vascular wall inflammation, using only acute phase responses is not reliable in assessing current disease activity. Therefore, physical examination and new imaging findings should also be used to …

The In Vitro Effect Of Antimicrobial Photodynamic Therapy Oncandida And Staphylococcus Biofilms, Özlem Güzel Tunçcan, Ayşe Kalkanci, Eli̇f Ayça Ünal, Olkar Abdulmajed, Merve Erdoğan, Murat Di̇zbay, Kayhan Çağlar

Turkish Journal of Medical Sciences

Background/aim: This study was designed to evaluate the effect of antimicrobial photodynamic treatment (APDT) in a biofilm model using combinations of various dyes (rose bengal, riboflavin, and methylene blue) as photosensitizers and light sources (LED and UVA) against staphylococcal and candidal biofilms. Materials and methods: Sterile microtiter plates were used for the development and quantification of the biofilms. APDT was carried out using combinations of the light sources and dyes. The percentage of the growth inhibition was then calculated using a spectrophotometer. The broth media in the wells were aspirated, wells were stained with crystal violet, and optical density values …

Gene Knockout Of Prfa And The Arginine Deiminase Pathway In Listeria Monocytogenes, Kearstin Edmonds

Online Theses and Dissertations

Listeria monocytogenes is a Gram-positive facultative intracellular pathogen. This species is a common cause of food-borne illness outbreaks with high fatality rates. L. monocytogenes is known to produce a number of virulence factors, including enzymes and toxins, which are involved in the disease process. The arginine deiminase pathway has the ability to regulate acidic environments by converting arginine to ammonia, ornithine, and ATP. With the help of a membrane-bound antiporter, the ornithine is transported out of the cell while the ammonia is converted to ammonium. The ATP by-product can also be used with the F0F1-ATPase system to help maintain homeostasis. …

Precise And Efficient Nucleotide Substitution Near Genomic Nick Via Noncanonical Homology-Directed Repair, Kazuhiro Nakajima, Yue Zhou, Akiko Tomita, Yoshihiro Hirade, Channabasavaiah B. Gurumurthy, Shinichiro Nakada

Journal Articles: Munroe-Meyer Institute

CRISPR/Cas9, which generates DNA double-strand breaks (DSBs) at target loci, is a powerful tool for editing genomes when codelivered with a donor DNA template. However, DSBs, which are the most deleterious type of DNA damage, often result in unintended nucleotide insertions/deletions (indels) via mutagenic nonhomologous end joining. We developed a strategy for precise gene editing that does not generate DSBs. We show that a combination of single nicks in the target gene and donor plasmid (SNGD) using Cas9D10A nickase promotes efficient nucleotide substitution by gene editing. Nicking the target gene alone did not facilitate efficient gene editing. However, an additional …

The Function Of Erbin, A Scaffold Protein, As A Tumor Suppressor In Colon Cancer, Payton D. Stevens

Theses and Dissertations--Molecular and Cellular Biochemistry

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that play important roles in orchestrating cell signaling. Here, we show that Erbin functions as a tumor suppressor in colon cancer. Analysis of Erbin expression in patient specimens reveals that Erbin is downregulated at both mRNA and protein levels in tumor tissues. Functionally, knockdown of Erbin disrupts epithelial cell polarity and increases cell proliferation in 3D culture. In addition, silencing Erbin results in an increase in the amplitude and duration of signaling through Akt and RAS/RAF pathways. Moreover, Erbin-loss induces epithelial-mesenchymal transition (EMT), which coincides with …

Workplace Standing Desks And Arterial Stiffness, Ian Greenlund

Dissertations, Master's Theses and Master's Reports

Many jobs in today’s society require sitting at a desk with little physical activity. Individuals who engage in ten hours of sedentary behavior per day double their CVD risk. Standing desks are thought to decrease sedentary time and improve cardiovascular health. Acute use of standing desks is shown to lower PWV. However, chronic effects remain unknown. Forty eight participants qualified as seated (19 females, 5 males: age 41 ± 2 years, BMI 25 ± 1 kg/m²) or standing (21 females, 3 males: age 45 ± 2 years, BMI 25 ± 1 kg/m²) groups based on habitual …

The Meiosis-Specific Cdc20 Family-Member Ama1 Promotes Binding Of The Ssp2 Activator To The Smk1 Map Kinase., Gregory Omerza, Chong Wai Tio, Timothy Philips, Aviva Diamond, Aaron M. Neiman, Edward Winter

Department of Biochemistry and Molecular Biology Faculty Papers

Smk1 is a meiosis-specific MAP kinase (MAPK) in budding yeast that is required for spore formation. It is localized to prospore membranes (PSMs), the structures that engulf haploid cells during meiosis II (MII). Similar to canonically activated MAPKs, Smk1 is controlled by phosphorylation of its activation-loop threonine (T) and tyrosine (Y). However, activation loop phosphorylation occurs via a noncanonical two-step mechanism in which 1) the cyclin-dependent kinase activating kinase Cak1 phosphorylaytes T207 during MI, and 2) Smk1 autophosphorylates Y209 as MII draws to a close. Autophosphorylation of Y209 and catalytic activity for substrates require Ssp2, a meiosis-specific protein that is …

Regulation Of Prostaglandin D2 And Angiogenesis-Related Factors From Human Skin Mast Cells By Interleukin-6 And Resveratrol, Cody Cody Mchale

Theses and Dissertations

Mast cells are classically recognized as the effector cells of Immunoglobulin E (IgE)-mediated hypersensitivity reactions (i.e. allergic reactions). Mast cells also play an important role in the innate immune response to parasitic helminth infection. Allergic disease including allergic rhinitis, asthma, atopic dermatitis, and anaphylaxis, is a major health concern in the United States with greater than 60 million Americans suffering from allergy and asthma. In addition, mast cells have more recently been implicated in non-allergic disease including various human cancers, which will affect approximately 39.6% of U.S. men and women. Therefore, understanding the immunological and molecular mechanisms that regulate mast …

Role Of Cox2 In Cellular Senescence, Mingxiao Feng

Theses and Dissertations

The survivors of childhood cancers are often associated with adverse late effects including hypoplasia, fatigue, and infertility, which are characteristics of aging. However, the underlying mechanisms of the late effects of chemotherapy are still elusive. We have found that transgenic cyclooxygenase-2 (COX2) expression causes premature aging phenotypes. Since COX2 expression is highly induced by various chemotherapeutic agents, we further investigated the possible link between COX2 and the late effects of chemotherapy. Treatment of juvenile wild-type mice with doxorubicin (DOX), an anthracycline-based chemotherapeutic agent, resulted in premature aging phenotypes and escalated cellular senescence level in various tissues. We found that tissue …