Digital Commons Network^™

Building Kcnq1/Kcne1 Channel Models And Probing Their Interactions By Molecular-Dynamics Simulations, Yu Xu, Yuhong Wang, Xuan-Yu Meng, Mei Zhang, Min Jiang, Meng Cui, Gea-Ny Tseng

Physiology and Biophysics Publications and Presentations

The slow delayed rectifier (I_Ks) channel is composed of KCNQ1 (pore-forming) and KCNE1 (auxiliary) subunits, and functions as a repolarization reserve in the human heart. Design of I_Ks-targeting anti-arrhythmic drugs requires detailed three-dimensional structures of the KCNQ1/KCNE1 complex, a task made possible by Kv channel crystal structures (templates for KCNQ1 homology-modeling) and KCNE1 NMR structures. Our goal was to build KCNQ1/KCNE1 models and extract mechanistic information about their interactions by molecular-dynamics simulations in an explicit lipid/solvent environment. We validated our models by confirming two sets of model-generated predictions that were independent from the spatial restraints used …

S3-S4 Linker Length Modulates The Relaxed State Of A Voltage-Gated Potassium Channel, Michael F. Priest, Jérôme J. Lacroix, Carlos A. Villalba-Galea, Fancisco Bezanilla

Physiology and Biophysics Publications and Presentations

Abstract

Voltage-sensing domains (VSDs) are membrane protein modules found in ion channels and enzymes that are responsible for a large number of fundamental biological tasks, such as neuronal electrical activity. The VSDs switch from a resting to an active conformation upon membrane depolarization, altering the activity of the protein in response to voltage changes. Interestingly, numerous studies describe the existence of a third distinct state, called the relaxed state, also populated at positive potentials. Although some physiological roles for the relaxed state have been suggested, little is known about the molecular determinants responsible for the development and modulation of VSD …

Wicking: A Rapid Method For Manually Inserting Ion Channels Into Planar Lipid Bilayers, Justin A. Costa, Dac A. Nguyen, Egdar Leal-Pinto, Ronald E. Gordon, Basil Hanss

Physiology and Biophysics Publications and Presentations

The planar lipid bilayer technique has a distinguished history in electrophysiology but is arguably the most technically difficult and time-consuming method in the field. Behind this is a lack of experimental consistency between laboratories, the challenges associated with painting unilamellar bilayers, and the reconstitution of ion channels into them. While there has be a trend towards automation of this technique, there remain many instances where manual bilayer formation and subsequent membrane protein insertion is both required and advantageous. We have developed a comprehensive method, which we have termed “wicking”, that greatly simplifies many experimental aspects of the lipid bilayer system. …

Challenging Pre-Service Students' Teaching Perspectives In An Inquiry-Focused Program, J. L. Pecore, A. Shelton

Journal of Mathematics and Science: Collaborative Explorations

Inquiry teaching based on constructivist learning theory has been an emphasis in pre-service education for over a decade. In general, a developmental teaching perspective supports inquiry-based instruction where teachers view learners as constructors of knowledge and teaching as providing questions, problems, and challenges that form a bridge from the learners' prior knowledge to a new, more sophisticated form of reasoning. Since teaching perspectives influence student learning, teacher effectiveness, and teacher attrition, challenging pre-service teachers to overcome experience-based convictions of a transmission perspective is necessary in teacher education. In this study, we examined the teaching perspectives of secondary, pre-service methods students …

(Pre)Determined Occupations: The Post-Colonial Hybridizing Of Identity And Art Forms In Third World Spaces, Amanda Alexander, Manisha Sharma

Journal of Social Theory in Art Education

In this article, we present the effects of globalization on art forms in Peru and on teacher identity in India while exploring hybridization as an ongoing global paradigm in both contexts (Bhabha, 1994; Said, 1979). Peruvian art forms are continuously shifting as global cultures meld and become more technologically connected, which ultimately brings about questions of authenticity. The identities of Indian art educators are evolving, and shifting indicating an assemblage or structure containing many parts working together to perform a particular function. In realizing its function, the structure can be named or its form made visible (Deleuze & Guattari, 1987). …

Reviews And Responses: Brown And Spitzer’S Public Folklore, Kristin G. Congdon

Journal of Social Theory in Art Education

Book review for Public Folklore, Robert Baron and N. R. Spitzer (Editors), Smithsonian Institution, Washington, 1992.

Discovering Protein Functions And Career Goals: The Suppressor Sike, Rebekah Rifareal

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Discovering IMSD was accidental. I was having a routine advising appointment and discussing future careers when the topic surfaced. At the time, I had no clue about what I wanted to do, so my advisor suggested that I explore research and encouraged me to apply for the program.

Inquiry Teaching: It Is Easier Than You Think!, S. Key, D. Owens

Journal of Mathematics and Science: Collaborative Explorations

This article is a survey of the literature on inquiry teaching. Many teachers do not participate in inquiry teaching for various reasons. The following are the main reasons: it takes too much time; students do not learn what they need for the state test; and, the teachers do not know how to grade projects and presentations. These reasons sound like rhetoric from long ago, but it is very current. In this article, research is used to show that students who participate in inquiry learning or any type of problem-based education do much better than students who do not have that …

Examining The Relationship Between Particulate Matter, Nitrogen Oxide, Carbon Oxides, Sulfur Dioxide And Hypertension In Urban Areas In India: A Review, Hiren Kolli

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

While blood pressure may be decreasing around the world, it has been on the rise in India (Kounteya, 2012). According to the World Health Organization, the average blood pressure went down by 2.7mm Hg among women globally, while increasing by 2.4mm Hg in India. In men, blood pressure decreased by 2.3mm Hg globally in the past three decades but increased by 2.2mm Hg in India (Kounteya, 2012). Almost three-quarters of people with hypertension live in developing countries with limited health resources where there is very low awareness of hypertension, and India is one of these countries. Hypertension is the leading …

Closing The Gap: A Research Agenda For The Study Of Health Needs Among American Indian/Native Hawaiian Transgender Individuals, Irene S. Vernon, Trudie Jackson

Ethnic Studies Review

Objectives: To explore health research needs of American Indian and Native Hawaiian (AIINH) transgender individuals. Methods: This qualitative study is composed of four focus groups and one informal meeting, totaling 42 AIINH transgender individuals in four major cities. The theoretical and methodological approaches combined grounded theory with the principles of community based participatory research. Results: Healthcare and resiliency are two main themes that emerged as research needs with important subcategories within them. Access to quality care from medical professionals and access to care that is unique to their trans gender status were subcategories within healthcare. Lived experiences, culture, and history …

Re:Creation, Heather Boone

Theses and Dissertations

This intent of this project is to explore the importance of handmade objects in the age of information.

Major Depressive Disorder And Measures Of Cellular Aging: An Integrative Review, Patricia Anne Kinser, Debra E. Lyon

School of Nursing Publications

Major depressive disorder (MDD) affects millions of individuals and causes significant suffering worldwide. It has been speculated that MDD is associated with accelerated aging-related biological and functional decline. To examine the accelerated aging hypothesis, one of the biomarkers under study is leukocyte telomeres, and specifically the measure of telomere length and telomerase activity. This review integrates findings from eleven human studies which evaluated telomere length and telomerase activity, in order to synthesize the state of the current science and to inform the development of new knowledge and enhance nursing research of depression using appropriate biobehavioral measures. Although preliminary, the findings …

Elucidation Of Mechanisms Generating 5-Hydroxymethylcytosine (5hmc) In Mammalian Mitochondria, Prashant Thakkar

Theses and Dissertations

DNA methylation plays a pivotal role in governing cellular processes including genomic imprinting, gene expression, and development. Recently, the Tet family of methylcytosine dioxygenases(Tet1, Tet2 and Tet3) was found to catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an intermediate in the pathway of DNA demethylation. Tet enzymes catalyze this hydroxylation in a 2-oxoglutarate and Fe2+ dependent manner. We have recently reported significant levels of 5mC and 5hmC modification in immunoprecipitates of mammalian mitochondrial DNA(mtDNA). We provide the first evidence that a DNA Methyltransferase-1 isoform (mtDNMT1) translocates to the mitochondria using an N-terminal mitochondrial targeting sequence. mtDNMT1 expression is …

Hormone Epimers Regulate Er Stress And Core Regulatory Genes: Network Analysis With Applications To Glioma And Chronic Pressure Ulcers, Thomas L. Shaak

Theses and Dissertations

DHEA has been determined to have medically significant activity and is the parent compound to the more active metabolites; 17α-AED, 17β-AED and 17β-AET, which exhibit strong biological activity that has been attributed to androgenic, estrogenic or anti-glucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED and 17β-AET for their ability to activate the human AR, ER and GR receptors and determine the relative androgenicity, estrogenicity and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, …

Assessment Of The Feasibility Of Co-Administration Of Phenolic Dietary Compounds With Phenylephrine To Increase Its Bioavailability, Zhenxian Zhang

Theses and Dissertations

R-(-)-Phenylephrine (PE) is the most commonly used nonprescription oral nasal decongestant in the United States. It is a selective α1-adrenergic receptor agonist and has many years of safe usage. However, the efficacy of PE is controversial, due to its extensive pre-systemic metabolism, which leads to low and variable oral bioavailability (38 ± 9%, mean ± SD). Sulfation plays a very important role in pre-systemic metabolism of PE. The sulfation of PE occurs at its phenolic group, which is the preferred structural feature of many sulfotransferase (SULT) substrates. Compounds with phenolic groups have similar structures to PE, which may share the …

In-Vitro Pk/Pd Profiling And Modeling Of The Anti-Sickling Agents, 5-Hydroxymethyl Furfural (5-Hmf) And Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) In Human Whole Blood, Apurvasena Parikh

Theses and Dissertations

Introduction. 5-HMF and novel INN-compounds are left-shifting AEH, shown to have anti-sickling action by forming transiently covalent Schiff-base adducts with hemoglobin (Hb), thereby increasing the Hb O2-affinity. They are hypothesized to be substrates for aldehyde dehydrogenase (ALDH) in the liver and red blood cells (RBC). Methods. Biopharmaceutical assessments were made for AEH, using calculated physicochemical properties. Their in-vitro hepatic metabolism (mediated by ALDH) was characterized using hepatic cytosol, and in-vitro-in-vivo extrapolations (IVIVE) were made. Inter-species differences in hepatic cytosolic ALDH activity were investigated using acetaldehyde as a model substrate in different mammalian species. Time- and concentration-dependent in-vitro disposition of 5-HMF …

Thc-Mediated Induction Of Δfosb And Its Modulation Of Cb1r Signaling And Adaptation, Lazenka Matthew

Theses and Dissertations

The main psychoactive and therapeutic effects of Δ9-tetrahydrocannabinol (THC) are mediated through cannabinoid type 1 receptors (CB1Rs). The therapeutic uses of THC are mitigated by the development of tolerance to these therapeutic effects, whereas tolerance does not readily develop to some of the side-effects of THC, like motor impairment and reward. The development of tolerance occurs through adaptations at CB1Rs, which include desensitization (G-protein uncoupling) and downregulation (receptor degradation). Brain region-dependent differences in THC-mediated adaptations are proposed to explain the differences in tolerance to various THC-mediated effects. These studies focused on whether ΔFosB, a stable transcription factor, could regulate CB1R …

Graphene-Supported Metal Nanoparticles For Applications In Heterogeneous Catalysis, Hany Elazab

Theses and Dissertations

Due to its unique properties and high surface area, Graphene has become a good candidate as an effective solid support for metal catalysts. The Nobel Prize in Physics for 2010 was awarded to Andre Geim and Konstantin Novoselov "for groundbreaking experiments regarding the two-dimensional material graphene". Microwave-assisted synthesis of various metallic nanostructured materials was investigated for CO oxidation applications. These metallic nanostructured materials were used to convert CO to CO2 as an effective approach for carbon monoxide elimination due to its harmful effect on health and environment. In particular, this dissertation is focusing on palladium as a transition metal that …

Incorporating Patient And Family Preferences Into Evidence-Based Medicine, Laura A. Siminoff

Social and Behavioral Sciences Publications

Background Clinicians are encouraged to practice evidence-based medicine (EBM) as well as patient-centered medicine. At times, these paradigms seem to be mutually exclusive and difficult to reconcile. It can become even more challenging when trying to include the preferences of the patient’s family members. This paper discusses the basis for this quandary, providing examples of the real-world impact it has on diagnosis-seeking and treatment decision-making behaviors and how it might inform implementation of EBM practices.

Analysis To further explore the role of friends and family in health-care decision making and to understand how patients and families introduce other considerations that …

Virginia Dental Journal (Vol. 90, No. 4, 2013)

Virginia Dental Journal

No abstract provided.

Association Between Concomitant Use Of Bisphosphonates And Serotonin Reuptake Inhibitors And Increased Risk Of Osteoporotic-Related Fractures: Among Community-Dwelling Postmenopausal Women, Abner Nyandege

Theses and Dissertations

Osteoporosis and depression are prevalent among older postmenopausal women 65 years or older. Bisphosphonates (BPs) and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) are commonly used medications to treat these conditions. Inhibitory effects of BPs on osteoclasts are responsible for the reduction in fracture risk. SSRIs, however, are associated with increased fracture risk through decreasing osteoblasts and increasing osteoclastic activity. These effects of SSRIs could attenuate the beneficial effects of BPs. This dissertation describes the concomitant use of BPs and SSRIs among postmeopausa women and reports findings from examining the association between concomitant use of BPs …

Autonomous Systems, Karolis Kosas

Theses and Dissertations

The ubiquity of digital media provides an unprecedented possibility to redefine the process and methods of design. Through experience from a series of creative projects, I investigate how certain aspects of the web allow for design to attain a degree of autonomy, thus producing results that go beyond anticipation and expertise of the author. Utilizing an unlimited capacity to store the content and retrieve immediate feedback, the designer’s role can be shifted to that of an initiator defining rules and boundaries, from which the process can evolve independently based on the input of users and data. The design output in …

A Review Of Literature On Teaching Evaluation, Martin Reardon

MERC Publications

The members of MERC’s Policy and Planning Council are well aware of the challenges that school divisions are facing as they conscientiously endeavor to honor the stipulations of the Guidelines (2011) in a loosely coupled system. In keeping with the context out of which the request for this literature review arose, a sense of the literature invoked in the Research Base (2011) has been taken for granted. The focus of this document, then, is on literature—predominantly recent literature—that addresses issues associated with the implementation of teacher evaluation. This emphasis on implementation is in keeping with MERC’s mission to engage in …

Multi-Culturalism & Alzheimer’S Disease: Patient-Centered Design As A New Care Model For Multi-Cultural Patients With Alzheimer’S Disease, Sang Ryu

Theses and Dissertations

The multi-cultural demographics of those who are diagnosed with Alzheimer’s disease should be closely examined. From a designer’s standpoint, its cultural traits can foster positive behaviors that lead to better quality of life for patients and caregivers. A patient-centered approach in design was explored in order to shape community-based care that empowers (1) individuality in care services, (2) interpersonal connection in caregiver–patient activities, and (3) a communal culture of being valued via humanitarian approaches.

Using Coaching As A Professional Development Modality To Train Teachers In The Use Of Evidence-Based Practices For Students With Autism Spectrum Disorders., Samantha Hollins

Theses and Dissertations

Professional development for teachers currently working in the classroom is an important focus of educational programs and school systems. Continuous professional development is especially important for special education teachers to maintain current information related to strategies and supports that are effective in educating students with disabilities. The increase in identification of students with autism has forced many teachers to quickly adapt to working with a population of students they have limited experience in teaching through preservice education and previous classroom experience. Coaching is a popular method for professional development delivery to special education teachers currently working in the classroom. This …

The Impact Of Imprecision In Hcv Viral Load Test Results On Clinicians’ Therapeutic Management Decisions And On The Economic Value Of The Test, Roberta M. Madej

Theses and Dissertations

Clinical laboratory test results are integral to patient management. Important aspects of laboratory tests’ contributions are the use of the test information and the role they have in facilitating efficient and effective use of healthcare resources. Methods of measuring those contributions were examined using quantitative HCV RNA test results (HCV VL) in therapeutic management decisions as a model. Test precision is important in those decisions; therefore, the clinical use was evaluated by studying the impact that knowledge of inherent assay imprecision had on clinicians’ decisions. A survey describing a simulated patient at a decision point for HCV triple-combination therapy management …

The Ticking Of The “Biological Clock”: Worry About Future Fertility In Nulliparous Women, Karen E. Kersting

Theses and Dissertations

Abstract

Title: The Ticking of the “Biological Clock”: Worry about Future Fertility in Nulliparous Women

By: Karen Kersting, M.A., M.S.

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2013.

Major Director: Kathleen M. Ingram, J.D., Ph.D.

Associate Professor of Psychology

Department of Psychology

Modern women are waiting until later in their lives to have children than women of previous generations, a trend influenced by a number of factors including financial stability, dating norms, and career goals and responsibilities. As women age, their fertility may decline …

Analysis Of Polyethylene Glycol In The Α-Hemolysin Nanopore, David M. Dancho

Theses and Dissertations

Nanopores have been shown to be a useful analytical tool for single molecule detection. They have been used to study the composition of DNA and other molecules of interest. These pores are usually α-hemolysin which is a toxin from Staphylococcus aureus or more recently nanoscale synthetic solid state pores. Now we are beginning to look at other molecules or proteins by sending them into the nanopores and measuring a characteristic partial current blockade. In this thesis we look at polyethylene glycol (PEG) as it enters and blocks current through a single alpha hemolysin pore. We report the effects of ionic …

Early Adolescent Nicotine Exposure Has Long-Lasting Effects On Cocaine-Induced Behaviors In Mice, Mai Alajaji

Theses and Dissertations

Nicotine is one of the most commonly used drugs among adolescent populations. Given the fact that adolescence is a unique developmental stage, during which nicotine has long-term effects on future drug-taking behavior, it is essential to understand how early exposure to nicotine during adolescence may affect the abuse liability of other drugs. We hypothesize that repeated exposure to low doses of nicotine in adolescence induce age-specific enhancement of the rewarding effects of several drugs of abuse in the conditioned place preference (CPP) test. Furthermore, we predict that these changes in behavioral responses are mediated by nicotine-induced brain region-specific increases in …

Kinetics And Mechanisms Of Accumulation For Liposomal Ciprofloxacin Into Rat Alveolar Macrophages, Sayeed Mossadeq

Theses and Dissertations

The kinetics and mechanism of accumulation for liposomal ciprofloxacin (Lipo-CPFX) into the rat alveolar macrophage NR8383 cells were studied in vitro, in comparison to unformulated ciprofloxacin (CPFX). Upon incubation with CPFX or Lipo-CPFX, cellular drug accumulation was determined from the cell lysates or efflux was from the extracellular media by fluorescence-HPLC. The accumulation for Lipo-CPFX reached the asymptotic values at ≥ 2 hours, which was a result of uptake and efflux. The uptake appeared to be due to liposomes, mediated via cellular energy-independent mechanism like lipid fusion. In contrast, the efflux appeared to be due to ciprofloxacin, partly cellular energy-dependent, …