Digital Commons Network^™

Cadherin-2 Is Required Cell Autonomously For Collective Migration Of Facial Branchiomotor Neurons, Jane K. Rebman, Kathryn E. Kirchoff, Gregory S. Walsh

Biology Publications

Collective migration depends on cell-cell interactions between neighbors that contribute to their overall directionality, yet the mechanisms that control the coordinated migration of neurons remains to be elucidated. During hindbrain development, facial branchiomotor neurons (FBMNs) undergo a stereotypic tangential caudal migration from their place of birth in rhombomere (r)4 to their final location in r6/7. FBMNs engage in collective cell migration that depends on neuron-to-neuron interactions to facilitate caudal directionality. Here, we demonstrate that Cadherin-2-mediated neuron-to-neuron adhesion is necessary for directional and collective migration of FBMNs. We generated stable transgenic zebrafish expressing dominant-negative Cadherin-2 (Cdh2ΔEC) driven by the islet1 promoter. …

Small Animal Thermal Support Device: Thermoregulation System For Scireq Flexivent Chamber, Alexander Dickey, Ashkhan Hojati, Matthew James, Kathleen Vermillera

Capstone Design Expo Posters

During ventilation induced lung injury (VILI) experiments, anesthetized mice lose the ability to regulate their core body temperature. Without maintaining homeostasis, the experimental data may be compromised due to changes in the rodent’s internal functions. Traditional heating techniques utilize a water circulation heating system that is unable to fit inside flexiVent ventilator testing chambers. The objective of this project is to design and build an automatic thermoregulatory feedback system to regulate the core body temperature of a mouse inside individual testing chambers throughout the duration of the experiment. The project deliverables include a functioning prototype that achieves safe and effective …

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …

Book Review: Built To Last, Melanie A. Kulesz

MGMT 641 Leadership Book Reviews

Book review of Built to Last: Successful Habits of Visionary Companies, by James C. Collins and Jerry I. Porras, written for the Spring 2016 Semester MGMT 641: Organizational Leadership and Project Team Management class.

Impaired Immunological Synapse In Sperm Associated Antigen 6 (Spag6) Deficient Mice, Lauren Folgosa Cooley, Mohey Eldin El Shikh, Wei Li, Rebecca C. Keim, Zhengang Zhang, Jerome F. Strauss, Zhibing Zhang, Daniel H. Conrad

Microbiology and Immunology Publications

Sperm associated antigen 6 (SPAG6), a component of the central apparatus of the “9 + 2” axoneme, plays a central role in ciliary and flagellar motility; but, its contribution to adaptive immunity and immune system development is completely unknown. While immune cells lack a cilium, the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. This prompted our hypothesis that SPAG6 critically regulates the formation and function of immunological synapses. Using bone marrow reconstitution studies of adult WT mice, we demonstrate that SPAG6 is expressed in primary …

The Prostaglandin E2-Ep3 Receptor Axis Regulates Anaplasma Phagocytophilum-Mediated Nlrc4 Inflammasome Activation, Xiaowei Wang, Dana K. Shaw, Holly L. Hammond, Fayyaz S. Sutterwala, Manira Rayamajhi, Kari Ann Shirey, Darren J. Perkins, Joseph V. Bonventre, Thangam S. Velayutham, Sean M. Evans, Kyle G. Rodino, Lauren Viebrock, Karen M. Scanlon, Nicholas H. Carbonetti, Jason A. Carlyon, Edward A. Miao, Jere W. Mcbride, Michail Kotsyfakis, Joao H. F. Pedra

Microbiology and Immunology Publications

Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads …

Tumor-Reactive Immune Cells Protect Against Metastatic Tumor And Induce Immunoediting Of Indolent But Not Quiescent Tumor Cells, Kyle K. Payne, Rebecca Keim, Laura Graham, Michael O. Idowu, Wen Wan, Xiang-Yang Wang, Amir A. Toor, Harry D. Bear, Masoud H. Manjili

Massey Comprehensive Cancer Center Publications

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25⁺ NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25⁺ NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor …

A Fluffy Friend Can Chase Stress Away, Jessica Mayfield

The Scope

With final exams looming, VCU students could play with friendly dogs at “Paws for Stress” events held by the Center for Human-Animal Interaction and University Counseling services. CHAI is studying whether interacting with therapy dogs really can lower your stress levels.

Children Exposed To Intimate Partner Violence: Identifying Differential Effects Of Family Environment On Children's Trauma And Psychopathology Symptoms Through Regression Mixture Models, Shelby Elaine Mcdonald, Sunny Shin, Rosalie Corona, Anna Maternick, Sandra A. Graham-Bermann, Frank R. Ascione, James Herbert Williams

Social Work Publications

The majority of analytic approaches aimed at understanding the influence of environmental context on children's socioemotional adjustment assume comparable effects of contextual risk and protective factors for all children. Using self-reported data from 289 maternal caregiver-child dyads, we examined the degree to which there are differential effects of severity of intimate partner violence (IPV) exposure, yearly household income, and number of children in the family on posttraumatic stress symptoms (PTS) and psychopathology symptoms (i.e., internalizing and externalizing problems) among school-age children between the ages of 7–12 years. A regression mixture model identified three latent classes that were primarily distinguished by …

Development Of A Translational Model To Screen Medications For Cocaine Use Disorder I: Choice Between Cocaine And Food In Rhesus Monkeys, Amy R. Johnson

Pharmacology and Toxicology Publications

Background

Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper.

Methods

Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43 mg/kg/injection) and food (0, 1, 3, or 10 1 g banana-flavored food pellets). During daily 5 h sessions, a single cocaine dose and …

Poictesme: An Anthology Of Literature And Art (2016)

Pwatem (Poictesme), 2006-

Poictesme (now Pwatem) is an anthology of literature and art from undergraduate students at Virginia Commonwealth University. It publishes poetry, prose and art of all kinds from talented undergraduate students of all majors.

Empathy Activators: Teaching Tools For Enhancing Empathy Development In Service-Learning Classes, Robin Everhart, Katie Elliott, Lynn E. Pelco, Deborah Westin, Rowena Briones, Emily Peron

Division of Community Engagement Resources

On February 5, 2016, 25 educators from Virginia Commonwealth University (VCU) and the University of Richmond (UR) gathered in Richmond, Virginia, for an annual service-learning workshop. This year’s workshop featured Robin Everhart, PhD, VCU assistant professor of psychology, as keynote speaker. Jumpstarted by Everhart’s research on student empathy, workshop participants explored the concept of empathy and collaboratively developed strategies for integrating empathy into the service-learning experience. This document grows out of Everhart’s presentation and group discussions during that workshop and represents a collection of ideas generated.

Core Competencies For Undergraduate Community-Engaged Researchers, Grant Wolfe

Community-Engaged Research Resources

Undergraduate community-engaged research (UCEnR) is a growing trend which VCU has proactively pursued by providing grants for UCEnR projects and assimilating UCEnR into interdisciplinary curricula. However, a definitive sense of core competencies for undergraduate community-engaged researchers has not yet been established. To that end, this literature review answers the question, "What skills should UCEnR students have?"

Dna Methylation Of Regulatory Regions Of Imprinted Genes At Birth And Its Relation To Infant Temperament, Bernard F. Fuemmeler, Chien-Ti Lee, Adelheid Soubry, Edwin S. Iversen, Zhiqing Huang, Amy P. Murtha, Joellen M. Schildkraut, Randy L. Jirtle, Susan K. Murphy, Cathrine Hoyo

Health Policy Publications

Background: DNA methylation of the differentially methylated regions (DMRs) of imprinted genes is relevant to neurodevelopment.

Methods: DNA methylation status of the DMRs of nine imprinted genes in umbilical cord blood leukocytes was analyzed in relation to infant behaviors and temperament (n = 158).

Results: MEG3 DMR levels were positively associated with internalizing (β = 0.15, P = 0.044) and surgency (β = 0.19, P = 0.018) behaviors, after adjusting for birth weight, gender, gestational age at birth, maternal age at delivery, race/ethnicity, education level, smoking status, parity, and a history of anxiety or depression. Higher methylation levels at the …

James Branch Cabell's Library [Dataset Pdf], Maurice Duke

James Branch Cabell's Library, A Catalogue: Dissertation by Maurice Duke

The contents of James Branch Cabell's library, presented as a PDF file, derived from Maurice Duke's 1968 dissertation James Branch Cabell's library : a catalogue.

Identification Of The Metabolic Enzyme Involved Morusin Metabolism And Characterization Of Its Metabolites By Ultraperformance Liquid Chromatogaphy Quadrupole Time-Of-Flight Mass Spectrometry (Uplc/Q-Tof-Ms/Ms), Xianbao Shi, Brianna Mackie, Gang Zhang, Shuman Yang, Yonggui Song, Dan Su, Yali Liu, Lina Shan

Pharmacology and Toxicology Publications

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from …

Examining The Pieces: Usability Testing To Improve Outreach To Unaffiliated Health Professionals, Emily J. Hurst, Irene Lubker, Barbara A. Wright

VCU Libraries Faculty and Staff Presentations

Objectives: In order to better address the information needs of unaffiliated public health and primary care professionals, librarians undertook a project to strengthen usability and refine the content of a freely available website maintained by the library. Collaboration with an advisory committee of local and state health care professionals allowed librarians to schedule focus groups and usability testing with diverse groups.

Methods: While a freely available, library maintained website had a long history, usability testing had not been done after a platform upgrade. Outside funding provided library staff with resources to engage with community groups focused on supporting public health …

Songbird’S Winter Grounds Face Environmental Threats, Kirby Farineau

The Scope

VCU graduate biology student Jessica Reese has documented the environmental threats facing the prothonotary warbler. Development has depleted the mangrove forests of Panama and Colombia where these gray and yellow songbirds spend the winter months.

Meditation On A Cat Picture And A Flamingo Statue, Lucas Alexander

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

I am a very visual person. As a student studying cinema, I’m interested in creating stories that can be woven together into a film. Even when something isn’t “supposed to” contain elements of narrative and fiction as defined by its medium, I do my very best to put them in there anyway. I want to make my own unique stories, in pictures and in words. Optimally, they end up being amusing.

When making anything, I tend to hack a jagged path through the whole mess as fast as possible, and have something technically defined as a finished product as soon …

Homo Heidelbergensis: The Tool To Our Success, Alexander Burkard

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Homo heidelbergensis, a physiological variant of the species Homo sapien, is an extinct species that existed in both Europe and parts of Asia from 700,000 years ago to roughly 300,000 years ago (carbon dating). This “subspecies” of Homo sapiens, as it is formally classified, is a direct ancestor of anatomically modern humans, and is understood to have many of the same physiological characteristics as those of anatomically modern humans while still expressing many of the same physiological attributes of Homo erectus, an earlier human ancestor. Since Homo heidelbergensis represents attributes of both species, it has therefore earned the classification as …

Prenatal Nicotine Exposure As A Teratogen In Neurological Pathways, Monica Grover

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Attention-deficit/hyperactivity disorder (ADHD) is the most heritable and commonly diagnosed childhood psychiatric disorder with 4% of all children being diagnosed with this disorder. Prenatal smoking has been found to be a risk factor for ADHD, a disorder that has been believed to be linked to the fluctuation of dopamine levels. Prenatal nicotine exposure in the second trimester influences dopaminergic neurological pathways by altering dopamine release levels. The altered dopamine levels make the fetus brain more sensitive to the nicotine, causing the nicotine exposure to be more dangerous in causing ADHD symptoms. Prenatal nicotine exposure alters the neurological pathway of the …

Exploring Pharmacological And Behavioral Mechanisms Involved In Alcohol Dependence During Adolescence, Rabha Mousa Younis

Theses and Dissertations

Alcoholism is a serious illness that is marked by uncontrollable drinking and physical dependence to alcohol. Long-term alcoholism has been linked to many health concerns such as cirrhosis of the liver and cardiovascular disease. Alcohol is one of the most commonly used drugs among adolescent populations. Given that adolescence is a unique developmental stage during which alcohol has long-term effects on future drug-taking behavior; it is essential to understand how early exposure to alcohol during adolescence may affect the abuse liability of the drug later in life. Indeed, most alcohol users start during adolescence suggesting that exposure to alcohol during …

Using Semiphysiologically-Based Pharmacokinetic (Semi-Pbpk) Modeling To Explore The Impact Of Differences Between The Intravenous (Iv) And Oral (Po) Route Of Administration On The Magnitude And Time Course Of Cyp3a-Mediated Metabolic Drug-Drug Interactions (Ddi) Using Midazolam (Mdz) As Prototypical Substrate And Fluconazole (Flz) And Erythromycin (Ery) As Prototypical Inhibitors, Mengyao Li

Theses and Dissertations

The purpose of the project was to investigate the impact of IV and PO routes difference for MDZ, a prototypical CYP3A substrate, and two CYP3A inhibitors (CYP3AI) -FLZ and ERY-, on the magnitude and time course of their inhibitory metabolic DDI.

Individual semi-PBPK models for MDZ, FLZ and ERY were developed and validated separately, using pharmacokinetic (PK) parameters from clinical/in-vitro studies and published physiological parameters. Subsequently, DDI sub-models between MDZ and CYP3AIs incorporated non-competitive and mechanism-based inhibition (MBI) for FLZ and ERY, respectively, on hepatic and gut wall (GW) CYP3A metabolism of MDZ, using available in-vitro/in-vivo information. Model-simulated MDZ …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Potential Treatments For Malformation Associated Epilepsy, Olivia M. Bowles

Theses and Dissertations

Epilepsy has been previously attributed to either increased excitation or decreased inhibition. With this closed frame of mind, modern medicine has been unable to develop a permanent treatment against the mechanisms of epilepsy. In order to treat patients with intractable seizures, especially those caused by developmental malformations, it is essential to understand the entirety of mechanisms that could possibly play a role in the abnormal cortical function. One such developmental malformation is known as polymicrogyria. Epileptogenesis occurs in an area laterally adjacent to this malformation known as the paramicrogyral region (PMR). Past studies have narrowed down the potential cause of …

Understanding And Targeting The C-Terminal Binding Protein (Ctbp) Substrate-Binding Domain For Cancer Therapeutic Development, Benjamin L. Morris

Theses and Dissertations

Cancer involves the dysregulated proliferation and growth of cells throughout the body. C-terminal binding proteins (CtBP) 1 and 2 are transcriptional co-regulators upregulated in several cancers, including breast, colorectal, and ovarian tumors. CtBPs drive oncogenic properties, including migration, invasion, proliferation, and survival, in part through repression of tumor suppressor genes. CtBPs encode an intrinsic dehydrogenase activity, utilizing intracellular NADH concentrations and the substrate 4-methylthio-2-oxobutyric acid (MTOB), to regulate the recruitment of transcriptional regulatory complexes. High levels of MTOB inhibit CtBP dehydrogenase function and induce cytotoxicity among cancer cells in a CtBP-dependent manner. While encouraging, a good therapeutic would utilize >100-fold …

Effects Of Olfactory Cues On The Movement Behavior Of The Predatory Beetle Calosoma Wilcoxi, Kennesha Myrick-Bragg

Theses and Dissertations

Arthropod predators often use prey and conspecific cues to make foraging decisions. Calosoma wilcoxi (Leconte) is a voracious predatory beetle that specializes on lepidopteran larvae often found in the forest canopy, including the fall cankerworm. This study tested the hypothesis that C. wilcoxi uses olfactory cues to detect prey and conspecifics. A Y-tube olfactometer was used to test attractiveness to larvae, larval frass, conspecific cues, and volatiles from herbivore-damaged white oak leaves. C. wilcoxi did not preferentially choose the treatment in any of the experiments. There was no difference in mean time spent in the treatment or control arm for …

Development And Characterization Of Lung Derived Extracellular Matrix Hydrogels, Robert A. Pouliot

Theses and Dissertations

Chronic obstructive pulmonary disease (COPD) including emphysema is a devastating condition, increasing in prevalence in the US and worldwide. There remains no cure for COPD, rather only symptomatic treatments. Due to unique challenges of the lung, translation of therapies for acute lung injury to target chronic lung diseases like COPD has not been successful. We have been investigating lung derived extracellular matrix (ECM) hydrogels as a novel approach for delivery of cellular therapies to the pulmonary system.

During the course of this work we have developed and characterized a lug derived ECM hydrogel that exhibits “injectability,” allowing cells or dugs …

An Injectable Stem Cell Delivery System For Treatment Of Musculoskeletal Defects, Shirae Leslie

Theses and Dissertations

The goal of this research was to develop a system of injectable hydrogels to deliver stem cells to musculoskeletal defects, thereby allowing cells to remain at the treatment site and secrete soluble factors that will facilitate tissue regeneration. First, production parameters for encapsulating cells in microbeads were determined. This involved investigating the effects of osmolytes on alginate microbead properties, and the effects of alginate microbead cell density, alginate microbead density, and effects of osteogenic media on microencapsulated cells. Although cells remained viable in the microbeads, alginate does not readily degrade in vivo for six months. Therefore, a method to incorporate …

Stains Induce Apoptosis And Autophagy In Primary And Transformed Mast Cells, Patrick A. Paez

Theses and Dissertations

Statin drugs are widely employed in the clinic to reduce serum low density lipoproteins (LDLs) in patients with hypocholesteremia. In addition to their cholesterol-lowering effects through HMG CoA reductase antagonism, isoprenyl lipids necessary for membrane anchorage and signaling of small G-proteins are abrogated. We previously found that statins suppress mast cell activation in murine and human cells, suggesting these drugs might be useful in treating allergic disease. While mast cell function is critical to allergic inflammation, mast cell hyperplasia and survival also impact these diseases, and were not studied in our previous work. In this study, we describe Fluvastatin-mediated apoptosis …