Digital Commons Network^™

Identification Of A Β-Arrestin-Biased Negative Allosteric Modulator For The Β2-Adrenergic Receptor, Michael Ippolito, Francesco De Pascali, Nathan Hopfinger, Konstantin E. Komolov, Daniela Laurinavichyute, Poli Adi Narayana Reddy, Leon A. Sakkal, Kyle Z. Rajkowski, Ajay P. Nayak, Justin Lee, Jordan Lee, Gaoyuan Cao, Preston S. Donover, Melvin Reichman, Stevens. An, Joseph M. Salvino, Raymond B. Penn, Roger S S. Armen, Charles P. Scott, Jeffrey L. Benovic

Department of Biochemistry and Molecular Biology Faculty Papers

Catecholamine-stimulated β2-adrenergic receptor (β2AR) signaling via the canonical Gs–adenylyl cyclase–cAMP–PKA pathway regulates numerous physiological functions, including the therapeutic effects of exogenous β-agonists in the treatment of airway disease. β2AR signaling is tightly regulated by GRKs and β-arrestins, which together promote β2AR desensitization and internalization as well as downstream signaling, often antithetical to the canonical pathway. Thus, the ability to bias β2AR signaling toward the Gs pathway while avoiding β-arrestin-mediated effects may provide a strategy to improve the functional consequences of β2AR activation. Since attempts to develop Gs-biased agonists and allosteric modulators for the β2AR have been largely unsuccessful, here we …

Far-Uvc: Technology Update With An Untapped Potential To Mitigate Airborne Infections, P. Jacob Bueno De Mesquita, Rosemary K. Sokas, Mary B. Rice, Edward A. Nardell

Arts & Sciences Faculty Publications

No abstract provided.

Deposited Cigarette Smoke As A Driver Of Oxidation And Partitioning Processes On Indoor Surfaces, April Hurlock

Honors Theses

Despite the large amount of time that individuals spend indoors during their lives, very little attention was paid to the chemistry that occurs on indoor surfaces until recently. Although not visible to the naked eye, physical and chemical processes, such as partitioning and oxidation, are occurring on virtually every indoor surface in a typical household. Indoor pollutants, ranging from skin oils to environmental cigarette smoke, drive a lot of these processes. The transformation of indoor surfaces by indoor pollutants can increase chemical exposure risks as new irritants or carcinogens can be introduced to the surfaces. In this thesis, I describe …

All In: How Colby Met Covid-19, Gerry Boyle

Colby Magazine

It was last August and first-years were arriving, unloading cars, lugging stuff into residence halls. President David A. Greene was on hand for the big day, meeting students, greeting parents, only to hear, “We expect to be back here within two weeks to a month to pick up our child.” It didn’t happen.

Development Of A Novel Vertebrate Pesticide For The Invasive Small Indian Mongoose, Carmen Antaky, Steven C. Hess, Israel Leinbach, Robert T. T. Sugihara, Emily W. Ruell, Shane Siers

USDA Wildlife Services: Staff Publications

Small Indian mongooses are detrimental introduced predators in the United States, where they depredate native species, serve as vector of disease, and threaten public safety. Due to the risk of accidental introduction to mongoose-free islands, high cost and limitations to trapping, and no national (Section 3) Environmental Protection Agency (EPA)-registered toxicants for mongoose control, there is a need for an efficacious toxic bait for mongooses for use in conservation areas and at points of entry in the United States. Over the last five years, the National Wildlife Research Center (NWRC) worked to develop a toxic bait for mongooses for registration …

Induction Of Antibiotic Activity Against Methicillin-Resistant Staphylococcus Aureus In Small Molecules Through Zinc Activation, Rachel Michaela Andrews

All ETDs from UAB

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious human pathogen with a staggering potential for multi-drug resistance. Because of this, the Centers for Disease Control and Prevention and the World Health Organization monitor the spread of MRSA and encourage antibiotic development efforts targeting this pathogen. Despite this, few antibiotics have been developed and brought to market in recent decades. To continue treating infections caused by this organism, we must identify novel antibiotic molecules with different mechanisms of action from known antibiotics. Bacterial copper-dependent inhibitors (CDIs), molecules that become antibacterial in the presence of copper (Cu), have been studied as a novel …

Unintended Consequences Of Air Cleaning Chemistry, Douglas B. Collins, Delphine K. Farmer

Faculty Journal Articles

Amplified interest in maintaining clean indoor air associated with the airborne transmission risks of SARS-CoV-2 have led to an expansion in the market for commercially available air cleaning systems. While the optimal way to mitigate indoor air pollutants or contaminants is to control (remove) the source, air cleaners are a tool for use when absolute source control is not possible. Interventions for indoor air quality management include physical removal of pollutants through ventilation or collection on filters and sorbent materials, along with chemically reactive processes that transform pollutants or seek to deactivate biological entities. This perspective intends to highlight the …

Zinc Finger Dna Repair Protein Targets Of Arsenite In The Nucleotide Excision Repair Pathway, Juliana M. Huestis

Biomedical Sciences ETDs

Environmental arsenic exposure affects around 100 million people worldwide. Recent evidence shows that arsenite, even at low concentrations, may act as a co-carcinogen, by displacing zinc from the zinc finger motifs of certain DNA repair proteins, leaving them vulnerable to redox modification and loss of protein function. This study probes the physical chemistry underlying arsenite and zinc binding to XPA and PARP1, in the hope of illuminating some of the aspects of protein structure that determine susceptibility to arsenite binding. In this study, dissociation constants are determined for zinc and arsenite binding to peptides corresponding to the C4 zinc finger …

Alternatives To Red Blood Cell Transfusions, Julia Prosser

Capstone Showcase

Abstract

Introduction: Allogenic red blood cell (RBC) transfusions are used for a number of different reasons. As with any medical procedure, allogenic RBC transfusions are not risk-free. Since the first recorded blood transfusion in 1655, the process has remained relatively unchanged. ABO incompatibility and contamination with infectious diseases are two major complications associated with RBC transfusions. Furthermore, traditional allogenic RBC transfusions have supply and demand issues. These issues, plus several more, could be alleviated with the use of artificial blood. This paper addresses the important clinical question: In patients who require RBC transfusions (P), is there a viable artificial blood …

Functional Magnetic Resonance Spectroscopy In First-Episode Schizophrenia: Measuring Glutamate And Glutathione Dynamics At 7-Tesla, Peter Jeon

Electronic Thesis and Dissertation Repository

Schizophrenia is a neuropsychiatric illness without known etiology or cure. Current efforts for symptom treatment still seem to leave a large portion of affected individuals without proper symptom management, with those experiencing symptom relief still having to wrestle with potential side-effects from medication trials. There has been growing evidence suggesting that glutamate and glutathione abnormalities hold major roles in development and manifestation of schizophrenia symptoms.

Magnetic resonance spectroscopy (MRS) provides a non-invasive means to observe in-vivo brain chemistry, including glutamate and glutathione. By adding a functional component to an MRS paradigm (fMRS), such as the color-word Stroop task, it is …

Preparation And Characterization Of Tio2-Sio2 Bioceramic Coating On Ti Alloy Via Electrochemical Anodization And Its Effect On Corrosion Resistance, Rasha Marzouk, Eatemad Shoreibah, Inas Motawae, Madiha Shoeib

Al-Azhar Journal of Dentistry

AbstractPurpose: The present study was carried out to study changing the anodization parameters and investigate the corrosion resistance of the ceramic coating that will be formed on the CP-Ti by anodization method. Materials and Methods: CP-Ti (10mm×10mm×2mm) were used for fabrication of bioceramic coating through anodization with different parameters using potassium silicate electrolyte. Samples were characterized using XRD, AT-FTIR. Surface roughness was measured using ESEM and surface topography was evaluated by SEM. Tafel polarization and electrochemical impedance spectroscopy were used to detect the change in the corrosion resistance after anodization. Results: XRD revealed that the anodized coated samples showed well …

Maternal Undernourishment In Guinea Pigs Leads To Fetal Growth Restriction With Increased Hypoxic Cells And Oxidative Stress In The Brain., Yohei Maki, Karen Nygard, Robert R Hammond, Timothy Regnault, Bryan S Richardson

Paediatrics Publications

BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress.

METHODS: Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR).

RESULTS: FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure …

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

General Chemistry Student Attitudes And Success With Use Of Online Homework: Traditional- Responsive Versus Adaptive-Responsive, Michelle Richards-Babb, Reagan Curtis, Betsy Ratcliff, Abhik Roy, Taylor Mikalik

Clinical and Translational Science Institute

We investigated whether use of an adaptive-responsive online homework system (OHS) that tailors homework to students’ prior knowledge and periodically reassesses students to promote learning through practice retrieval has inherent advantages over traditional-responsive online homework. A quasi-experimental cohort control post-test-only design with nonequivalent groups and propensity scores with nearest neighbor matching (n = 6,114 pairs) was used. The adaptive system was found to increase the odds of a higher final letter grade for average, below average, and failing students. However, despite the learning advantages, students self-reported less favorable attitudes toward adaptive-responsive (3.15 of 5) relative to traditional-responsive OHS (3.31). Specific …

Long-Term Safety And Efficacy Of Belimumab In Patients With Systemic Lupus Erythematosus A Continuation Of A Seventy-Six-Week Phase Iii Parent Study In The United States, R. A. Furie, D. J. Wallace, C. Aranow, J. Fettiplace, B. Wilson, P. Mistry, D. A. Roth, D. Gordon

Journal Articles

No abstract provided.

Oncology Of Different Populations And The Ethical Impact Of The Hela Cell Case And Physician Assisted Suicide On Patient Autonomy, Neha Bakshi

Senior Honors Theses and Projects

An in depth analysis of different types of cancers in various populations such as pediatrics, adults of all ages, and babies that are still in the womb. Discusses the importance of funding research and finding new methods of treatment. This explains the ethical impact of the Henrietta Lacks case and Physician Assisted Suicide (PAS) on patient autonomy and the importance of allowing patients to decide if they want to start or even continue cancer treatments.

Synthesis And Photophysical Studies Of Pyrrolocytosine Derivatives, Atefeh Rouhi

Electronic Thesis and Dissertation Repository

Pyrrolocytosine (pC) derivatives are used in the study of nucleic acid structure, function and in the design of the hybridization probes. They have unique properties including small size and Watson-Crick base pairing capability and impressive fluorescent properties. However, they exhibit variation in the fluorescence properties upon incorporation into single-stranded DNA and double-stranded DNA.

This study analyzes the effect of the nearest neighbours on the fluorescence properties of phenylpyrrolocytosine (PhpC) and provides a guide to the proper design of the PhpC containing fluorescent probes. Moreover, the possibility of photoinduced electron transfer (PET) as the underlying mechanism of the unusual photophysical behavior …

Pediatric Leukemia: Diagnosis To Treatment–A Review, Samantha C. Bernard, Ehab H. Abdelsamad, Paisley A. Johnson, Daniel L. Chapman, Madhukiran Parvathaneni

Faculty Works

Leukemia is cancer of the blood and bone marrow, it is the most common cancer found in children and is found to be more than one fourth of pediatric cancers. It causes white blood cells to become abnormal and the body to become weak. This deficiency in the immune system reduces the body's ability to fight infection or simple airborne illnesses, causing extensive treatment of common pathogens and cancer treatment. The present review covers all topics, from diagnosis to treatment of pediatric leukemia, as well as the stages of growth and physiological changes throughout the process. As leukemia has a …

Potential For Identifying Plant-Based Toxins On San Hunter-Gatherer Arrowheads, Madelien Wooding, Justin Bradfield, Vinesh Maharaj, Dwayne Koot, Lyn Wadley, Linda C. Prinsloo, Marlize Lombard

Faculty of Science, Medicine and Health - Papers: part A

The antiquity of the use of hunting poisons has received much attention in recent years. In this paper we present the results of a pilot study designed to detect the presence of organic compounds, typically of less than 1200 Da, from poisonous plants that may have been used as hunting poisons in the past. We used ultra-performance liquid chromatography connected to a Synapt G2 high-resolution MS-QTOF mass spectrometer (UPLC-QTOF-MS) to provisionally identify plant-based toxins present in (1) extracts of fresh plant material, (2) a blind control recipe consisting of three plant ingredients and (3) a Hei||om arrow poison of unknown …

Differences In Survival Times, By Gender, Among Those Diagnosed With Necrotizing Fasciitis, Ashley Elizabeth Hill

Walden Dissertations and Doctoral Studies

Necrotizing fasciitis infections have high mortality rates especially when treatment is delayed. Despite the abundance of research in many areas of necrotizing fasciitis infection, there are limited and conflicting studies focusing on gender-related outcomes for those diagnosed and died with necrotizing fasciitis infection. The purpose of this study was to determine the association that gender plays on survival time of patients who have been diagnosed with necrotizing fasciitis using a cross-sectional study design. Succeeding the conceptual design of the life course model, the research question tested whether there was a significant difference in survival time between the genders while in …

Predicting Academic Success Of Health Science Students For First Year Anatomy And Physiology, R Anderton, P Chivers

Paola Chivers

Students commencing tertiary education enter through a number of traditional and alternative academic pathways. As a result, tertiary institutions encounter a broad range of students, varying in demographic, previous education, characteristics and academic achievement. In recent years, the relatively constant increase in tertiary applications in Australia has not translated to an increase in student retention or graduate numbers. The Health Sciences discipline typically falls within this paradigm, prompting various approaches to promote academic success and overall student retention. In this study, the demographic and previous education of health science students at an Australian University, were analysed along with first year …

Predicting Academic Success Of Health Science Students For First Year Anatomy And Physiology, R Anderton, P Chivers

Health Sciences Papers and Journal Articles

Students commencing tertiary education enter through a number of traditional and alternative academic pathways. As a result, tertiary institutions encounter a broad range of students, varying in demographic, previous education, characteristics and academic achievement. In recent years, the relatively constant increase in tertiary applications in Australia has not translated to an increase in student retention or graduate numbers. The Health Sciences discipline typically falls within this paradigm, prompting various approaches to promote academic success and overall student retention. In this study, the demographic and previous education of health science students at an Australian University, were analysed along with first year …

Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale

Theses & Dissertations

Combination chemotherapy is commonly used to treat cancer, because such a therapy regimens usually involve sequential administration of multiple drugs and allow targeting different cell signaling pathway. The co-delivery of drug combination at a controlled ratio via the same vehicle is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and suppression of drug resistance. Undoubtedly, there are several molecular and pharmacological factors that determine the effectiveness of drug combinations. A rationally designed drug combination is required since certain drug ratios and the definitive exposure to the targets of interest can only be synergistic while others …

Elucidating The Role Of Injury-Induced Electric Fields (Efs) In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer, Scott C. Henderson, Raymond J. Colello

Anatomy and Neurobiology Publications

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Neuroinflammation And Neurologic Deficits In Diabetes Linked To Brain Accumulation Of Amylin, Sarah Srodulski, Savita Sharma, Adam B. Bachstetter, Jennifer M. Brelsfoard, Conrado Pascual, Xinmin Simon Xie, Kathryn E. Saatman, Linda J. Van Eldik, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

BACKGROUND: We recently found that brain tissue from patients with type-2 diabetes (T2D) and cognitive impairment contains deposits of amylin, an amyloidogenic hormone synthesized and co-secreted with insulin by pancreatic β-cells. Amylin deposition is promoted by chronic hypersecretion of amylin (hyperamylinemia), which is common in humans with obesity or pre-diabetic insulin resistance. Human amylin oligomerizes quickly when oversecreted, which is toxic, induces inflammation in pancreatic islets and contributes to the development of T2D. Here, we tested the hypothesis that accumulation of oligomerized amylin affects brain function.

METHODS: In contrast to amylin from humans, rodent amylin is neither amyloidogenic nor cytotoxic. …

Enhancing The Secondary-Tertiary Transition In Chemistry Through Formative Assessment And Self-Regulated Learning Environments, Gwen Lawrie, Chantal Bailey, Aaron Micallef, A R. Wright, Timothy Dargaville, Madeleine Schultz, Roy Tasker, Mark Williams, Simon B. Bedford, Glennys A. O'Brien

Faculty of Science, Medicine and Health - Papers: part A

It is desirable to enhance student learning trajectories between their secondary and tertiary studies while simultaneously encouraging them to take responsibility for their learning early in their tertiary studies. Their preparedness for tertiary studies in their discipline can be measured using diagnostic tests and this enables standards-based benchmarking as students progress through their tertiary program. Concept inventories have been used extensively for this purpose. A more desirable goal, however, is to use the outcomes of diagnostic testing to provide students with opportunities to improve their learning through formative feedback and self-regulated learning activities. We aim to design and implement modular, …

Allied Health Students’ Perceptions Of Class Difficulty: The Case Of Undergraduate Human Anatomy And Physiology Classes, Diana Sturges, Trent Mauner

Internet Journal of Allied Health Sciences and Practice

Purpose: The Human Anatomy and Physiology (HAP) course is required of all allied health majors. Students need to earn a grade of “C” or better, and many students find this class academically challenging. This study investigated allied health students’ perceptions of what makes the undergraduate class difficult. Methods: A 28-question survey targeted 403 students enrolled in three HAP sections taught by the same instructor. Results: Students returned 279 surveys (68% return rate). Qualitative and quantitative data supported a three factor model in making this class difficult: discipline, student, and teaching related factors. Students consider that discipline factors are more important …

Erosive Arthritis And Hepatic Granuloma Formation Induced By Peptidoglycan Polysaccharide In Rats Is Aggravated By Prasugrel Treatment., Analia E Garcia, Mario C Rico, Elisabetta Liverani, Raul A Dela Cadena, Paul F. Bray, Satya P Kunapuli

Cardeza Foundation for Hematologic Research

Administration of the thienopyridine P2Y12 receptor antagonist, clopidogrel, increased the erosive arthritis induced by peptidoglycan polysaccharide (PG-PS) in rats or by injection of the arthritogenic K/BxN serum in mice. To determine if the detrimental effects are caused exclusively by clopidogrel, we evaluated prasugrel, a third-generation thienopyridine pro-drug, that contrary to clopidogrel is mostly metabolized into its active metabolite in the intestine. Prasugrel effects were examined on the PG-PS-induced arthritis rat model. Erosive arthritis was induced in Lewis rats followed by treatment with prasugrel for 21 days. Prasugrel treated arthritic animals showed a significant increase in the inflammatory response, compared with …

Rapid Cascade Synthesis Of Poly-Heterocyclic Architectures From Indigo, Alireza Shakoori Ghasabi, John Bremner, Anthony C. Willis, Rachada Haritakun, Paul A. Keller

Faculty of Science, Medicine and Health - Papers: part A

The base-induced propargylation of the dye indigo results in the rapid and unprecedented one-pot synthesis of highly functionalized representatives of the pyrazino[1,2-a:4,3-a′]diindole, pyrido[1,2-a:3,4-b′]diindole and benzo[b]indolo[1,2-h]naphthyridine heterocyclic systems, with the last two reflecting the core skeleton of the anticancer/antiplasmodial marine natural products fascaplysin and homofascaplysins and a ring B-homologue, respectively. The polycyclic compounds 6–8, whose structures were confirmed through single-crystal X-ray crystallographic analysis, arise from sequential inter/intramolecular substitution–addition reactions, and in some cases, ring rearrangement reactions. Preliminary studies on controlling the reaction path selectivity, and the potential reaction mechanisms, are also described. Initial biological activity studies with these new heterocyclic derivatives …