Medicine and Health Sciences Commons^™

Allosteric Mechanism Of The Circadian Protein Vivid Resolved Through Markov State Model And Machine Learning Analysis, Hongyu Zhou, Zheng Dong, Gennady M. Verkhivker, Brian D. Zoltowski, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The fungal circadian clock photoreceptor Vivid (VVD) contains a photosensitive allosteric light, oxygen, voltage (LOV) domain that undergoes a large N-terminal conformational change. The mechanism by which a blue-light driven covalent bond formation leads to a global conformational change remains unclear, which hinders the further development of VVD as an optogenetic tool. We answered this question through a novel computational platform integrating Markov state models, machine learning methods, and newly developed community analysis algorithms. Applying this new integrative approach, we provided a quantitative evaluation of the contribution from the covalent bond to the protein global conformational change, and proposed an …

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Synthesis, Biological Evaluation And Molecular Modeling Studies Of Novel Chromone/Aza-Chromone Fused Α-Aminophosphonates As Src Kinase Inhibitors, S. Bapat, N. Viswanadh, M. Mujahid, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, M. Karthikeyan, M. Muthukrishnan, Renu Vyas

Pharmacy Faculty Articles and Research

A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase …

The Influence Of Unpredictable, Fragmented Parental Signals On The Developing Brain, Laura M. Glynn, Tallie Z. Baram

Psychology Faculty Articles and Research

Mental illnesses originate early in life, governed by environmental and genetic factors. Because parents are a dominant source of signals to the developing child, parental signals - beginning with maternal signals in utero - are primary contributors to children’s mental health. Existing literature on maternal signals has focused almost exclusively on their quality and valence (e.g. maternal depression, sensitivity). Here we identify a novel dimension of maternal signals: their patterns and especially their predictability/unpredictability, as an important determinant of children’s neurodevelopment. We find that unpredictable maternal mood and behavior presage risk for child and adolescent psychopathology. In experimental models, fragmented/unpredictable …

Src Family Kinase Inhibitors Block Translation Of Alphavirus Subgenomic Mrnas, Rebecca Broeckel, Sanjay Sarkar, Nicholas A. May, Jennifer Totonchy, Craig N. Kreklywich, Patricia Smith, Lee Graves, Victor R. Defilippis, Mark T. Heise, Thomas E. Morrison, Nathaniel Moorman, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Alphaviruses are arthropod-transmitted RNA viruses that can cause arthralgia, myalgia, and encephalitis in humans. Since the role of cellular kinases in alphavirus replication is unknown, we profiled kinetic changes in host kinase abundance and phosphorylation following chikungunya virus (CHIKV) infection of fibroblasts. Based upon the results of this study, we treated CHIKV-infected cells with kinase inhibitors targeting the Src family kinase (SFK)–phosphatidylinositol 3-kinase (PI3K)–AKT–mTORC signaling pathways. Treatment of cells with SFK inhibitors blocked the replication of CHIKV as well as multiple other alphaviruses, including Mayaro virus, O’nyong-nyong virus, Ross River virus, and Venezuelan equine encephalitis virus. Dissecting the effect of …

A Child With Congenital Aglossia: A Narrative Review And Descriptive Case Study, Betty Mcmicken

Communication Sciences and Disorders Faculty Articles and Research

This article details an account of a young female with congenial aglossia. Because of the low incidence of this anatomical and physiological presentation, this narrative review includes a brief historical review of the disorder and a detailed description of: (1) reports in the literature of congenital hypoglossia and aglossia, (2) characteristics of speech in children with congenital aglossia below the age of 18 years, and (3) the medical history, speech acquisition, and course of intervention of a 5-year-old girl with congenital aglossia currently in speech treatment.

The Promises And Challenges Of Erythropoietin For Treatment Of Alzheimer's Disease, Jiahong Sun, Jan Michelle Martin, Victoria Vanderpoel, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder in the world, and intracellular neurofibrillary tangles and extracellular amyloid-beta protein deposits represent the major pathological hallmarks of the disease. Currently available treatments provide some symptomatic relief but fail to modify primary pathological processes that underlie the disease. Erythropoietin (EPO), a hematopoietic growth factor, acts primarily to stimulate erythroid cell production, and is clinically used to treat anemia. EPO has evolved as a therapeutic agent for neurodegeneration and has improved neurological outcomes and AD pathology in rodents. However, penetration of the blood–brain barrier (BBB) and negative hematopoietic effects are the two …

Exploring In Silence: Hearing And Deaf Infants Explore Objects Differently Before Cochlear Implantation, Mary K. Fagan

Communication Sciences and Disorders Faculty Articles and Research

Infant development has rarely been informed by the behavior of infants with sensory differences despite increasing recognition that infant behavior itself creates sensory learning opportunities. The purpose of this study of object exploration was to compare the behavior of hearing and deaf infants, with and without cochlear implants, in order to identify the effects of profound sensorineural hearing loss on infant exploration before cochlear implantation, the behavioral effects of access to auditory feedback after cochlear implantation, and the sensory motivation for exploration behaviors performed by hearing infants as well. The results showed that 9-month-old deaf infants explored objects as often …

Promoting Support For Public Health Policies Through Mediated Contact: Can Narrator Perspective And Self-Disclosure Curb In-Group Favoritism?, Riva Tukachinsky, Emily Brogan-Freitas, Tessa Urbanovich

Communication Faculty Articles and Research

An online 2 × 2 factorial experiment (N = 203) examined the effect of parasocial contact on support for public health policies in the context of opioid addiction. We hypothesize that because of an intergroup dynamic, individuals are less likely to engage with an outgroup character than an in-group character featured in a news magazine article. Results support the in-group favoritism hypothesis. The study examines two narrative devices for overcoming this tendency: the narrator’s perspective and amount of insight into the character’s inner world through character self-disclosure. We find support for the narrator perspective but not for the self-disclosure effect. …

Track 1.B Introduction: Re-Designing Health: Transforming Systems, Practices And Care, Aidan Rowe, Claudine Jaenichen, Gillian Harvey, Kate Sellen, Stephanie Vandenberg

Art Faculty Articles and Research

The Re-Designing Health: Transforming Systems, Practices and Care track explores the increasing role and possibility for a wide range of design practices and methods to contribute to health care products, provision, and systems.

There is growing recognition of the increasing complexity faced by healthcare systems; critical issues and challenges include ageing populations, chronic diseases, growing drug ineffectiveness, and lack of access to comprehensive services (to name only a few examples). Concurrently design thinking, methods and practices are increasingly recognized as means of addressing complex, multi-levelled and systemic problems.

The track session brought together design academics, researchers and practitioners that are …

Actionable Patient Safety Solutions (Apss) #3a: Medication Errors, Ron Jordan, Jerika Lam, Peter Antevy, Steven Barker, Linda Beneze, Michel Bennett, Laressa Bethishou, Jim Broselow, John Burnam, Mitchell Goldenstein, Kari Hamlin, Helen Haskell, Christopher Jerry, Edwin Loftin, Ariana Longley, Jacob Lopez, Anne Lyren, Brendan Miney, Sidney Morice, Steve Mullenix, Robert Nickell, Rochelle Sandell, David Shane Lowry, Robin Shannon, Deeba Siddiqui, Charles Simmons, Nat Sims, Robert Stein, Laura Townsend, Jason Yamaki, Sun Yang

Pharmacy Faculty Articles and Research

A medication error is a preventable event in any healthcare setting that may lead to inappropriate medication use while in the control of the healthcare professional or patient, ultimately leading to patient harm and/or death. Medication errors can be classified into five categories: 1) wrong drug, 2) wrong dose, 3) wrong route, 4) wrong frequency and/or 5) wrong patient.

Actionable Patient Safety Solutions (Apss) #6: Hand-Off Communications, Steven Barker, Nick Adams, Misti B. Baskett, Victoria Baskett, Michael Becker, Michel Bennett, Laressa Bethishou, Mike Ramsay, Jeff Dunn, Hisham El-Bayar, William Floyd, Frank Gencorelli, Christina Hazekamp, Kristy Blomquist, Edwin Loftin, Ariana Longley, Jacob Lopez, David Lubarsky, Pete Melrose, Brent Nibarger, Karen Rehling, Patricia Roth, Kris Stegner, Laura Townsend

Pharmacy Faculty Articles and Research

Hand-off communications, or hand-off processes, involve the transition of care as well as the transfer of patient-specific information by one healthcare professional to another with the purpose of providing a patient with safe, continuous care. A successful hand-off can only be achieved by effective communication.

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …