Medicine and Health Sciences Commons^™

(R)-Β-Lysine Modified Elongation Factor P Functions In Translation Elongation, Tammy J. Bullwinkle, S. Betty Zou, Andrei Rajkovic, Steven J. Hersch, Sara Elgamal, Nathaniel Robinson, David Smil, Yuri Bolshan, William Wiley Navarre, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Post-translational modification of bacterial elongation factor P (EF-P) with (R)-β-lysine at a conserved lysine residue activates the protein in vivo and increases puromycin reactivity of the ribosome in vitro. The additional hydroxylation of EF-P at the same lysine residue by the YfcM protein has also recently been described. The roles of modified and unmodified EF-P during different steps in translation, and how this correlates to its physiological role in the cell, have recently been linked to the synthesis of polyproline stretches in proteins. Polysome analysis indicated that EF-P functions in translation elongation, rather than initiation as proposed previously. This was …

Circularized Synthetic Oligodeoxynucleotides Serve As Promoterless Rna Polymerase Iii Templates For Small Rna Generation In Human Cells, Christine I. Seidl, Lodoe Lama, Kevin Ryan

Publications and Research

Synthetic RNA formulations and viral vectors are the two main approaches for delivering small therapeutic RNA to human cells. Here we report findings supporting an alternative strategy in which an endogenous human RNA polymerase (RNAP) is harnessed to make RNA hairpin-containing small RNA from synthetic single-stranded DNA oligonucleotides. We report that circularizing a DNA template strand encoding a pre-microRNA hairpin mimic can trigger its circumtranscription by human RNAP III in vitro and in human cells. Sequence and secondary structure preferences that appear to promote productive transcription are described. The circular topology of the template is required for productive transcription, at …

Selection Of Trna Charging Quality Control Mechanisms That Increase Mistranslation Of The Genetic Code, Srujana S. Yadavalli, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mistranslation can follow two events during protein synthesis: production of non-cognate amino acid:transfer RNA (tRNA) pairs by aminoacyl-tRNA synthetases (aaRSs) and inaccurate selection of aminoacyl-tRNAs by the ribosome. Many aaRSs actively edit non-cognate amino acids, but editing mechanisms are not evolutionarily conserved, and their physiological significance remains unclear. To address the connection between aaRSs and mistranslation, the evolutionary divergence of tyrosine editing by phenylalanyl-tRNA synthetase (PheRS) was used as a model. Certain PheRSs are naturally error prone, most notably a Mycoplasma example that displayed a low level of specificity consistent with elevated mistranslation of the proteome. Mycoplasma PheRS was found …

Neuroanatomical Substrates Of The Disruptive Effect Of Olanzapine On Rat Maternal Behavior As Revealed By C-Fos Immunoreactivity, Changjiu Zhao, Ming Li

Department of Psychology: Faculty Publications

Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0 mg/kg, sc). Maternal behavior was tested 2 h later, after which rats were sacrificed and brain tissues were collected. …

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

Transfusion Of Cxcr4-Primed Endothelial Progenitor Cells Reduces Cerebral Ischemic Damage And Promotes Repair In Db/Db Diabetic Mice, Ji Chen, Jianying Chen, Shuzhen Chen, Cheng Zhang, Liangqing Zhang, Xiang Xiao, Avik Das, Yuhui Zhao, Bin Yuan, Mariana Morris, Bin Zhao, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

This study investigated the role of stromal cell-derived factor-1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) axis in brain and endothelial progenitor cells (EPCs), and explored the efficacy of CXCR4 primed EPCs in treating ischemic stroke in diabetes. The db/db diabetic and db/+ mice were used in this study. Levels of plasma SDF-1α and circulating CD34+CXCR4+ cells were measured. Brain SDF-1α and CXCR4 expression were quantified at basal and after middle cerebral artery occlusion (MCAO). In in vitro study, EPCs were transfected with adenovirus carrying null (Ad-null) or CXCR4 (Ad-CXCR4) followed with high glucose (HG) treatment for 4 days. For pathway block …

Ambiguity, Ambivalence, And Apprehensions Of Taking Hiv-1 Pre-Exposure Prophylaxis Among Male Couples In San Francisco: A Mixed Methods Study, Parya Saberi, Kristine Elizabeth Gamarel, Torsten B. Neilands, Megan Comfort, Nicolas Sheon, Lynae A. Darbes, Mallory O. Johnson

Publications and Research

Objective: We conducted a mixed-methods study to examine serodiscordant and seroconcordant (HIV-positive/HIVpositive) male couples’ PrEP awareness, concerns regarding health care providers offering PrEP to the community, and correlates of PrEP uptake by the HIV-negative member of the couple.

Design: Qualitative sub-study included one-on-one interviews to gain a deeper understanding of participants’ awareness of and experiences with PrEP and concerns regarding health care providers offering PrEP to men who have sex with men (MSM). Quantitative analyses consisted of a cross-sectional study in which participants were asked about the likelihood of PrEP uptake by the HIV-negative member of the couple and level …

Reviewing The American University Law Review On Extraterritoriality: A Critical Response To Viki Economides, Note, Tianrui Group Co. V. Itc: The Dubious Status Of Extraterritoriality And The Domestic Industry Requirement Requirement Of Section 337(Link), Jonathan Stroud

Articles in Law Reviews & Other Academic Journals

Recently, the Federal Circuit upheld the Commission’s decision to exclude goods based on a trade secret violation that largely happened abroad. The American University Law Review critiqued that decision on two grounds: First, that a presumption against extraterritorial application of U.S. law applied; and second, that licensing alone could not establish a domestic industry. The American University Law Review's critique remains incomplete, however, as the Federal Circuit correctly decided the case for at least two reasons. first, the Federal Circuit correctly applied the “extraterritorial presumption” canon of construction; and second, the recent Federal Circuit decision in InterDigital Communications LLC v. …

Molecular Mechanism For Depolarization-Induced Modulation Of Kv Channel Closure, Alain J. Labro, Jerome J. Lacroix, Carlos A. Villalba-Galea, Dirk J. Snyders, Francisco Bezanilla

School of Pharmacy Faculty Articles

Voltage-dependent potassium (Kv) channels provide the repolarizing power that shapes the action potential duration and helps control the firing frequency of neurons. The K(+) permeation through the channel pore is controlled by an intracellularly located bundle-crossing (BC) gate that communicates with the voltage-sensing domains (VSDs). During prolonged membrane depolarizations, most Kv channels display C-type inactivation that halts K(+) conduction through constriction of the K(+) selectivity filter. Besides triggering C-type inactivation, we show that in Shaker and Kv1.2 channels (expressed in Xenopus laevis oocytes), prolonged membrane depolarizations also slow down the kinetics of VSD deactivation and BC gate closure during the …

Asthma Knowledge, Adherence, And Administration Techniques In Hispanic Caregivers Of Pediatrics, Joshua Arnold, Rachel Culp, Kyle Hultz, Benjamin Robertson, Jon Wilkie, Amy Wuobio, Marty L. Eng, Kelly J. Hiteshew

Pharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session

7.5% of Hispanics in the United States suffer from asthma-related diseases, and Latino children are not as likely to use preventative asthma medications as compared with Caucasians. Educational interventions may reduce the number of visits to emergency-care. The reasons for non-adherence are currently unknown, and discovering these reasons will help to address the problem.

Anabolic And Androgenic Effects Of Certain Atriplex Species Grown In Egypt, Dina M. El-Kersh, Fatma S. El-Sakhawy, Dina R. Abou-Hussein, Amany A. Sleem

Pharmacy

20-Hydroxyecdysone (20-HE) was detected by TLC in the ethyl acetate fraction of two Atriplex species grown in Egypt: A. lindleyi subsp. inflata and A. leucoclada. EIA quantification of 20-HE proved its presence in a concentration of 9.15 and 7.3 μg/g dried aerial parts in each of the two species, respectively. Significant anabolic and androgenic activities were demonstrated for 20-HE comparing to testosterone; the study also revealed that the total alcohol extract and the ethyl acetate fraction of A. lindleyi subsp. inflata exhibited greater activities than their analogues in A. leucoclada. Column chromatographic fractionation of the ethyl acetate fraction of the …

A Human Phospholipid Phosphatase Activated By A Transmembrane Control Module, Christian R. Halaszovich, Michael G. Leitner, Angeliki Mavrantoni, Audrey Le, Ludivine Frezza, Anja Feuer, Daniela N. Schreiber, Carlos A. Villalba-Galea, Dominik Oliver

School of Pharmacy Faculty Articles

In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P(2). In the chimera, enzymatic activity …

A Review Of Literature Regarding North American Parent’S Perceptions About The Hpv Vaccine And The Effect They Have On Vaccine Uptake In Their Adolescent Daughters Ages 9 To 26, Francesca Couser, Jessica Dahnke

Pharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session

A woman dies every 2 minutes due to HPV related illness. Cervical cancer is the 5th most common cancer worldwide, with approximately 471,000 new cases diagnosed each year. There is a decreased risk of HPV related illnesses with vaccine development. However, lack of uptake is suspected to be impacted by parental knowledge deficit. Previously, these illnesses received little attention by parents and healthcare providers, even with the very evident increase in newly diagnosed patients. Without education, rate of infection will continue to increase as vaccine uptake remains stagnant. The purpose of this study is to determine how education from healthcare …

A Comparison Of The Effect Of Intermittent And Continuous Infusion Of Meropenem On The Prevalence Of Nausea In Pediatric Cystic Fibrosis Patients, Marissa Cushing, Juanita A. Draime, Bao-Ngoc Ho, Jordan Nicholls, Bethany Sibbitt, Rebecca Widder, Rebecca J. Gryka, Denise S. Simpson

Pharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session

Cystic Fibrosis (CF) is a genetic disease, leading to changes of membrane secretions causing obstruction of smaller airways. CF patients often develop pulmonary infections and require antibiotic treatment. Meropenem is a broad spectrum beta lactam that acts by lysing microbes through interfering with bacterial cell wall synthesis. Although a safe and effective treatment, data on pediatric patients is limited.

The Effects Of Supplemental Fish Oil On Blood Pressure And Morning Cortisol In Normotensive Adults: A Pilot Study, Eric E. Noreen, Josef Brandauer

Health Sciences Faculty Publications

Purpose: To determine the effects of 6wk of supplementation with fish oil (FO) on blood pressure and the morning salivary cortisol concentration in normotensive adults.

Methods: Testing was performed following an overnight fast. Subjects (n=40; 35+/-13y, mean+/-SD) rested supine for 40 min, at which time blood pressure and heart rate were measured. Saliva was collected and analyzed for cortisol. Subjects were then randomly assigned to either: 4g/d of Safflower Oil (SO); pr 4g/d of FO supplying 1,600mg/d eicosapentaenoic acid and 800mg/d docosahexaenoic acid. Testing was repeated following 6wk treatment.

Results: Compared to SO, there was a significant decrease …

Edible Marijuana: A New Frontier In The Culinary World, Ariella H. Wolkowicz

Honors Theses - Providence Campus

Cannabis, commonly known as marijuana, has a rich history as a source of fiber, food and medicine (Li 437). Since 1785, physicians and scientists alike have worked to discover the active chemical components and medical effectiveness of this plant (Touw 2; Aldrich). Despite its complicated legal history, marijuana has retained a place culturally and, in some countries, scientifically as an effective medical agent. As a medically edible ingredient, cannabis has also been more recently heralded as a new, even cutting edge flavor, opening a new frontier to the culinary community.

After the isolation of the main active ingredient in cannabis, …

Pediatric Pharmacogenomics: A Systematic Assessment Of Ontogeny And Genetic Variation To Guide The Design Of Statin Studies In Children., Jonathan B. Wagner, J Steven Leeder

Manuscripts, Articles, Book Chapters and Other Papers

The dose-exposure-response relationship for drugs may differ in pediatric patients compared with adults. Many clinical studies have established drug dose-exposure relationships across the pediatric age spectrum; however, genetic variation was seldom included. This article applies a systematic approach to determine the relative contribution of development and genetic variation on drug disposition and response using HMG-CoA reductase inhibitors as a model. Application of the approach drives the collection of information relevant to understanding the potential contribution of ontogeny and genetic variation to statin dose-exposure-response in children, and identifies important knowledge deficits to be addressed through the design of future studies.

Drug–Drug Conditioning Between Citalopram And Haloperidol Or Olanzapine In A Conditioned Avoidance Response Model: Implications For Polypharmacy In Schizophrenia, Nathan L. Sparkman, Ming Li

Department of Psychology: Faculty Publications

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. …

Situation Analysis Of Child Labour In Karachi, Pakistan: A Qualitative Study, Asaad Ahmed Nafees, Kausar S. Khan, Zafar Fatmi, Mubashir Aslam

Community Health Sciences

In Karachi, large employment opportunities, burgeoning population and the availability of cheap labour might be the contributing factors for the increasing prevalence of child labour. A literature review was conducted in 2007 that included published and unpublished literature since 2000. Various organizations working in the field were also covered, while the perception of the child labourers was covered through three focus group discussions. Common health issues among the child labourers in Karachi included respiratory illnesses, fever and generalised pains, as well as drug and sexual abuse. Organisations working for child labour could be broadly categorised into those working for legal …

Voltage-Controlled Enzymes: The New Janus Bifrons, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The Ciona intestinalis voltage-sensitive phosphatase, Ci-VSP, was the first Voltage-controlled Enzyme (VEnz) proven to be under direct command of the membrane potential. The discovery of Ci-VSP conjugated voltage sensitivity and enzymatic activity in a single protein. These two facets of Ci-VSP activity have provided a unique model for studying how membrane potential is sensed by proteins and a novel mechanism for control of enzymatic activity. These facets make Ci-VSP a fascinating and versatile enzyme. Ci-VSP has a voltage sensing domain (VSD) that resembles those found in voltage-gated channels (VGC). The VSD resides in the N-terminus and is formed by four …

Borrelia Burgdorferi Cp32 Bpab Modulates Expression Of The Prophage Nucp Nuclease And Ssbp Single-Stranded Dna-Binding Protein, Alicia M. Chenail, Brandon L. Jutras, Claire A. Adams, Logan H. Burns, Amy Bowman, Ashutosh Verma, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Borrelia burgdorferi BpaB proteins of the spirochete's ubiquitous cp32 prophages are DNA-binding proteins, required both for maintenance of the bacteriophage episomes and for transcriptional regulation of the cp32 erp operons. Through use of DNase I footprinting, we demonstrate that BpaB binds the erp operator initially at the sequence 5′-TTATA-3′. Electrophoretic mobility shift assays indicated that BpaB also binds with high affinity to sites located in the 5′ noncoding regions of two additional cp32 genes. Characterization of the proteins encoded by those genes indicated that they are a single-stranded DNA-binding protein and a nuclease, which we named SsbP and NucP, …

Human Endometrial Stromal Stem Cells Differentiate Into Megakaryocytes With The Ability To Produce Functional Platelets, Jinju Wang, Shuzhen Chen, Cheng Zhang, Samantha Stegeman, Teresa Pfaff-Amesse, Ying Zhang, Wenfeng Zhang, Lawrence Amesse, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Human endometrium is a high dynamic tissue that contains endometrial stromal stem cells (hESSCs). The hESSCs have been differentiated into a number of cell lineages. However, differentiation of hESSCs into megakaryocytes (MKs) has not yet been investigated. The aim of this study was to investigate the feasibility of MK generation from hESSCs and subsequent production of functional platelets (PLTs). In our study, hESSCs were cultured from endometrial stromal cells as confirmed by positive stromal cell specific markers (CD90 and CD29) and negative hematopoietic stem cell markers (CD45 and CD34) expression. Then, hESSCs were differentiated in a medium supplemented with thrombopoietin …

Development Of A Men’S Preference For Testosterone Replacement Therapy (P-Trt) Instrument, Sheryl L. Szeinbach, Enrique Seoane-Vazquez, Kent H. Summers

Pharmacy Faculty Articles and Research

Background: This study used a standard research approach to create a final conceptual model and the Preference for the Testosterone Replacement Therapy (P-TRT) instrument.

Methods: A discussion guide was developed from a literature review and expert opinion to direct one-on-one interviews with participants who used testosterone replacement therapy and consented to participate in the study. Data from telephone interviews were transcribed for theme analysis using NVivo 9 qualitative analysis software, analyzed descriptively from a saturation grid, and used to evaluate men’s P-TRT. Data from cognitive debriefing for five participants were used to evaluate the final conceptual model and …

Identification Of The Functional Binding Pocket For Compounds Targeting Small-Conductance Ca2+-Activated Potassium Channels, Miao Zhang, John M. Pascal, Marcel Schumann, Roger S. Armen, Ji-Fang Zhang

Pharmacy Faculty Articles and Research

Small- and intermediate-conductance Ca2+-activated potassium channels, activated by Ca2+-bound calmodulin, play an important role in regulating membrane excitability. These channels are also linked to clinical abnormalities. A tremendous amount of effort has been devoted to developing small molecule compounds targeting these channels. However, these compounds often suffer from low potency and lack of selectivity, hindering their potentials for clinical use. A key contributing factor is the lack of knowledge of the binding site(s) for these compounds. Here we demonstrate by X-ray crystallography that the binding pocket for the compounds of the 1-EBIO class is located at the calmodulin-channel interface. We …

Taking Aim At The Start Of Translation, Medha Raina, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

No abstract provided.

Quantification And In Vitro Analysis Of Nanolipoproteins (Nlps) Containing Adjuvants, Purna Venkataraman, Craig Blanchette, Nicholas O. Fischer

STAR Program Research Presentations

Nanolipoprotein particles (NLPs) self-assemble into nanoscale structures that can be used as vaccines or drug delivery agents. Due to the nature of the NLPs, a variety of immune stimulating compounds or adjuvants can be readily incorporated into NLPs: a characteristic difficult to engineer into most other nanoscale platforms. In light of this, a method for quantifying the amount adjuvant actually incorporated into NLPs is a question of high importance. Through the use of reverse phase High-Performance Liquid Chromatography (HPLC) and an Evaporative Light Scattering Detector (ELSD), standard curves can be constructed by analyzing mixtures of NLP components of known concentration, …

Effects Of Pristane On Growth Of Pink Salmon (Oncorhynchus Gorbuscha), Brielle D. Kemis, Bonita Nelson

STAR Program Research Presentations

Pristane is a naturally occurring hydrocarbon that is generated by copepods in marine ecosystems. Organisms that eat copepods do not readily metabolize pristane, which causes it to accumulate throughout the marine food web. Understanding how pristane affects marine fish is essential because pristane is often used as a bioindicator in lab studies and may be influencing results in those studies. Also, this hydrocarbon may significantly reduce growth of marine fish in the wild. A previous study indicated that pristane is an appetite suppressant and growth retardant in fish. However, the study implemented a feeding regime with unnaturally high levels of …

Parametric Studies Of Antipsychotic-Induced Sensitization In The Conditioned Avoidance Response Model: Roles Of Number Of Drug Exposure, Drug Dose, And Test–Retest Interval, Natashia Swalve, Ming Li

Department of Psychology: Faculty Publications

Repeated haloperidol and olanzapine treatment produces an enhanced disruption of avoidance responding, a validated measure of antipsychotic activity. Experimental parameters affecting this sensitization-like effect have not been thoroughly examined. The present study investigated the role of three parameters (number of injections, dose, and interval between initial exposure and challenge) in antipsychotic sensitization in the conditioned avoidance response paradigm. Well-trained Sprague–Dawley rats received different numbers of drug treatment (1–5 days) or different doses of haloperidol (0.025–0.10 mg/kg, subcutaneously) or olanzapine (0.5–2.0 mg/kg, subcutaneously). After certain time intervals (4, 10 or 17 days), they were tested for the expression of haloperidol or …

Prolonged Intermediate Syndrome Pue To Prganophosphate Poisoning, Nadeem Ullah Khan, Muhammad Junaid Patel, M. N.M. Hifath, Saima Kamal, Syed Ather Hussain

Department of Emergency Medicine

Organophosphate poisoning can present as acute cholinergic syndrome, Intermediate syndrome and delayed neuropathy. Intermediate syndrome secondary to organophosphate poisoning is a serious health problem leading to increased morbidity and mortality. The incidence of problem varies and range from 8%-84% of organophosphate poisoning cases. The factors account for this difference is nature of organophosphate compound, severity of poisoning and inadequate Oxime therapy. The recognition of this syndrome is important as organophosphate poisoning is common in our country. We presented this case of organophosphate poisoning leading to prolonged intermediate syndrome. The muscle weakness associated with this syndrome generally resolves in 5-18 days …

The Effect Of Pre-Operative Coumadin Therapy On Patients Who Develop Hemorrhagic Events Post Bariatric Surgery, Richard Boorse Md, Peter J. Bechtel Md, Cathleen Webber Rn, Mshs, Suzanne L. Smith Mba, Rrt, Tas, Cathy Fuhrman Rn, Msn

Department of Surgery

No abstract provided.