Digital Commons Network^™

Turning Over A New Leaf: Cannabinoid And Endocannabinoid Modulation Of Immune Function, Guy A. Cabral, Thomas J. Rogers, Aron H. Lichtman

Microbiology and Immunology Publications

Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids. The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1 and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of synthetic cannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system. This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 receptors that they activate. Endocannabinoids have been …

Hiv Protease Inhibitors Sensitize Human Head And Neck Squamous Carcinoma Cells To Radiation By Activating Endoplasmic Reticulum Stress, Runping Liu, Luyong Zhang, Jing Yang, Xiaoxuan Zhang, Ross B. Mikkelsen, Shiyu Song, Huiping Zhou

Microbiology and Immunology Publications

Background

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that …

Widely Used Herpes Simplex Virus 1 Icp0 Deletion Mutant Strain Dl1403 And Its Derivative Viruses Do Not Express Glycoprotein C Due To A Secondary Mutation In The Gc Gene, Cristina W. Cunha, Kathryne E. Taylor, Suzanne M. Pritchard, Mark Delboy, Tri Komala Sari, Hector C. Aguilar, Karen L. Mossman, Anthony V. Nicola

Microbiology and Immunology Publications

Herpes simplex virus 1 (HSV-1) ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1 dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1 dl1403 gC gene is predicted to encode a polypeptide …

Epigenetic Modifications Of The Pgc-1Α Promoter During Exercise Induced Expression In Mice, Timothy L. Lochmann, Ravindar R. Thomas, James P. Bennett Jr., Shirley M. Taylor

Microbiology and Immunology Publications

The transcriptional coactivator, PGC-1α, is known for its role in mitochondrial biogenesis. Although originally thought to exist as a single protein isoform, recent studies have identified additional promoters which produce multiple mRNA transcripts. One of these promoters (promoter B), approximately 13.7kb upstream of the canonical PGC-1α promoter (promoter A), yields alternative transcripts present at levels much lower than the canonical PGC-1α mRNA transcript. In skeletal muscle, exercise resulted in a substantial, rapid increase of mRNA of these alternative PGC-1α transcripts. Although the β2-adrenergic receptor was identified as a signaling pathway that activates transcription from PGC-1α promoter B, it is not …

Essential Domains Of Anaplasma Phagocytophilum Invasins Utilized To Infect Mammalian Host Cells, David Seidman, Kathryn S. Hebert, Hilary K. Truchan, Daniel P. Miller, Brittney K. Tegels, Richard T. Marconi, Jason A. Carlyon

Microbiology and Immunology Publications

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Luen Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …

Intracellular Uropathogenic E. Coli Exploits Host Rab35 For Iron Acquisition And Survival Within Urinary Bladder Cells, Neha Dikshit, Pradeep Bist, Shannon N. Fenlon, Niyas Kudukkil Pulloor, Christelle En Lin Chua, Marci A. Scidmore, Jason A. Carlyon, Bor Len Tang, Swaine L. Chen, Bindu Sukumaran

Microbiology and Immunology Publications

Recurrent urinary tract infections (UTIs) caused by uropathogenic E. coli (UPEC) are common and morbid infections with limited therapeutic options. Previous studies have demonstrated that persistent intracellular infection of bladder epithelial cells (BEC) by UPEC contributes to recurrent UTI in mouse models of infection. However, the mechanisms employed by UPEC to survive within BEC are incompletely understood. In this study we aimed to understand the role of host vesicular trafficking proteins in the intracellular survival of UPEC. Using a cell culture model of intracellular UPEC infection, we found that the small GTPase Rab35 facilitates UPEC survival in UPEC-containing vacuoles …

Orientia Tsutsugamushi Ankyrin Repeat-Containing Protein Family Members Are Type 1 Secretion System Substrates That Traffic To The Host Cell Endoplasmic Reticulum, Lauren Viebrock, Sean M. Evans, Andrea R. Beyer, Charles L. Larson, Paul A. Beare, Hong Ge, Smita Singh, Kyle G. Rodino, Robert A. Heinzen, Allen L. Richards, Jason A. Carlyon

Microbiology and Immunology Publications

Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and …

Increased B Cell Adam10 In Allergic Patients And Th2 Prone Mice, Lauren Folgosa Cooley, Rebecca K. Martin, Hannah B. Zellner, Anne-Marie Irani, Cora Uram-Tuculescu, Mohey Eldin El Shikh, Daniel H. Conrad

Microbiology and Immunology Publications

ADAM10, as the sheddase of the low affinity IgE receptor (CD23), promotes IgE production and thus is a unique target for attenuating allergic disease. Herein, we describe that B cell levels of ADAM10, specifically, are increased in allergic patients and Th2 prone WT mouse strains (Balb/c and A/J). While T cell help augments ADAM10 expression, Balb WT B cells exhibit increased ADAM10 in the naïve state and even more dramatically increased ADAM10 after anti-CD40/IL4 stimulation compared C57 (Th1 prone) WT B cells. Furthermore, ADAM17 and TNF are reduced in allergic patients and Th2 prone mouse strains (Balb/c and A/J) compared …

Essential Domains Of Anaplasma Phagocytophilum Invasins Utilized To Infect Mammalian Host Cells, David Seidman, Kathryn S. Hebert, Hilary K. Truchan, Daniel P. Miller, Brittney K. Tegels, Richard T. Marconi, Jason A. Carlyon

Microbiology and Immunology Publications

Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x …

Phylogenetic And Syntenic Data Support A Single Horizontal Transference To Atrypanosoma Ancestor Of A Prokaryotic Proline Racemase Implicated In Parasite Evasion From Host Defences, Zuleima C. Caballero, Andre G. Costa-Martins, Robson C. Ferreira, João M P Alves, Myrna G. Serrano, Erney P. Camargo, Gregory A. Buck, Paola Minoprio, Marata M G Teixeira

Microbiology and Immunology Publications

Background

Proline racemase (PRAC) enzymes of Trypanosoma cruzi (TcPRAC), the agent of Chagas disease, and Trypanosoma vivax (TvPRAC), the agent of livestock trypanosomosis, have been implicated in the B-cells polyclonal activation contributing to immunosuppression and the evasion of host defences. The similarity to prokaryotic PRAC and the absence in Trypanosoma brucei andTrypanosoma congolense have raised many questions about the origin, evolution, and functions of trypanosome PRAC (TryPRAC) enzymes.

Findings

We identified TryPRAC homologs as single copy genes per haploid genome in 12 of 15Trypanosoma species, including T. cruzi and T. cruzi …

Hiv Protease Inhibitors Sensitize Human Head And Neck Squamous Carcinoma Cells To Radiation By Activating Endoplasmic Reticulum Stress, Runping Liu, Luyong Zhang, Jing Yang, Xiaoxuan Zhang, Ross Mikkelsen, Shiyu Song, Huiping Zhou

Microbiology and Immunology Publications

Background

Human head and neck squamous cell carcinoma (HNSCC) is the sixth most malignant cancer worldwide. Despite significant advances in the delivery of treatment and surgical reconstruction, there is no significant improvement of mortality rates for this disease in the past decades. Radiotherapy is the core component of the clinical combinational therapies for HNSCC. However, the tumor cells have a tendency to develop radiation resistance, which is a major barrier to effective treatment. HIV protease inhibitors (HIV PIs) have been reported with radiosensitizing activities in HNSCC cells, but the underlying cellular/molecular mechanisms remain unclear. Our previous study has shown that …

Mri Evaluation Of Lumbar Disc Degenerative Disease, Pokhraj Suthar, Rupal Patel, Chetan Mehta, Narrotam Patel

Orthopaedic Surgery Publications

Introduction:

Lower back pain secondary to degenerative disc disease is a condition that affects young to middle-aged persons with peak incidence at approximately 40 y. MRI is the standard imaging modality for detecting disc pathology due to its advantage of lack of radiation, multiplanar imaging capability, excellent spinal soft-tissue contrast and precise localization of intervertebral discs changes.

Aims and Objective:

To evaluate the characterization, extent, and changes associated with the degenerative lumbar disc disease by Magnetic Resonance Imaging.

Study Design:

Cross-sectional and observational study.

Materials and Methods:

A total 109 patients of the lumbar disc degeneration with age group between …

Role Of Nitric Oxide In The Radiation-Induced Bystander Effect, Vasily A. Yakovlev

Radiation Oncology Publications

Cells that are not irradiated but are affected by “stress signal factors” released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role …

Virginia Commonwealth University Professional Bulletin [2015], Virginia Commonwealth University

VCU Bulletins

Professional programs bulletin for Virginia Commonwealth University for the academic year 2015-2016. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for graduate programs.

Annual Higher Ground Women's Leadership Conference 2015, The Grace E. Harris Leadership Institute At Virginia Commonwealth University

The Grace E. Harris Leadership Institute Publications

No abstract provided.

Virginia Commonwealth University Courses [2015], Virginia Commonwealth University

VCU Bulletins

Listing of courses for the 2015-2016 academic year.

Prehospital Use Of Plasma In Traumatic Hemorrhage (The Pupth Trial): Study Protocol For A Randomised Controlled Trial, Penny S. Reynolds, Mary Jane Michael, Emily D. Cochran, Jacob A. Wegelin, Bruce D. Spiess

Anesthesiology Publications

Background

Severe traumatic injury and haemorrhagic shock are frequently associated with disruptions of coagulation function (such as trauma-induced coagulopathy TIC) and activation of inflammatory cascades. These pathologies may be exacerbated by current standard of care resuscitation protocols. Observational studies suggest early administration of plasma to severely-injured haemorrhaging patients may correct TIC, minimise inflammation, and improve survival. The proposed randomised clinical trial will evaluate the clinical effectiveness of pre-hospital plasma administration compared with standard- of-care crystalloid resuscitation in severely-injured patients with major traumatic haemorrhage.

Methods/design

This is a prospective, randomized, open-label, non-blinded trial to determine the effect of pre-hospital administration of …

Building Community-Engagement Infrastructure At Warp Speed: Leveraging Enterprise Data And Partnerships, Valerie Holton, Kathleen Shaw

Division of Community Engagement Resources

This was presented at the pre-conference workshop on November 16, 2015 at the annual meeting of IARSLCE in Boston, Massachusetts.

Burr Hole Washout Versus Craniotomy For Chronic Subdural Hematoma: Patient Outcome And Cost Analysis, Jacqueline M. Regan, Emmagene Worley, Christopher Shelburne, Ranjit Pullarkat, Joseph C. Watson

Neurosurgery Publications

Chronic subdural hematomas (CSDH), which are frequently encountered in neurosurgical practice, are, in the majority of cases, ideally treated with surgical drainage. Despite this common practice, there is still controversy surrounding the best surgical procedure. With lack of clear evidence of a superior technique, surgeons are free to base the decision on other factors that are not related to patient care. A retrospective chart review of 119 patients requiring surgical drainage of CSDH was conducted at a large tertiary care center over a three-year period. Of the cases reviewed, 58 patients underwent craniotomy, while 61 patients underwent burr hole washout. …

Metagenomic Analysis Of Planktonic Microbial Consortia From A Non-Tidal Urban-Impacted Segment Of James River, Bonnie L. Brown, Rebecca V. Leprell, Rima B. Franklin, Maria C. Rivera, Francine M. Cabral, Hugh L. Eaves, Vicki Gardiakos, Kevin P. Keegan, Timothy L. King

Biology Publications

Knowledge of the diversity and ecological function of the microbial consortia of James River in Virginia, USA, is essential to developing a more complete understanding of the ecology of this model river system. Metagenomic analysis of James River's planktonic microbial community was performed for the first time using an unamplified genomic library and a 16S rDNA amplicon library prepared and sequenced by Ion PGM and MiSeq, respectively. From the 0.46-Gb WGS library (GenBank:SRR1146621; MG-RAST:4532156.3), 4 × 10 ⁶ reads revealed >3 × 10 ⁶ genes, 240 families of prokaryotes, and 155 families of eukaryotes. From the 0.68-Gb 16S library (GenBank:SRR2124995; …

Wat Yarn Rangsee, Chantana Moapichai

RELS 108 Human Spirituality: Student Perspectives

Student perspectives on worship services from Instructor Jennifer Garvin-Sanchez's Religious Studies 108 Human Spirituality course at Virginia Commonwealth University.

Outcomes For Implementation Science: An Enhanced Systematic Review Of Instruments Using Evidence-Based Rating Criteria, Cara C. Lewis, Sarah Fischer, Bryan J. Weiner, Cameo Stanick, Mimi Kim, Ruben G. Martinez

Psychology Publications

Background

High-quality measurement is critical to advancing knowledge in any field. New fields, such as implementation science, are often beset with measurement gaps and poor quality instruments, a weakness that can be more easily addressed in light of systematic review findings. Although several reviews of quantitative instruments used in implementation science have been published, no studies have focused on instruments that measure implementation outcomes. Proctor and colleagues established a core set of implementation outcomes including: acceptability, adoption,appropriateness, cost, feasibility, fidelity, penetration, sustainability (Adm Policy Ment Health Ment Health Serv Res 36:24–34, …

A Simple Method For Discovering Druggable, Specific Glycosaminoglycan-Protein Systems. Elucidation Of Key Principles From Heparin/Heparan Sulfate-Binding Proteins, Aurijit Sarkar, Umesh R. Desai

Psychology Publications

Glycosaminoglycans (GAGs) affect human physiology and pathology by modulating more than 500 proteins. GAG-protein interactions are generally assumed to be ionic and nonspecific, but specific interactions do exist. Here, we present a simple method to identify the GAG-binding site (GBS) on proteins that in turn helps predict high specific GAG–protein systems. Contrary to contemporary thinking, we found that the electrostatic potential at basic arginine and lysine residues neither identifies the GBS consistently, nor its specificity. GBSs are better identified by considering the potential at neutral hydrogen bond donors such as asparagine or glutamine sidechains. Our studies also reveal that an …

Virginia Commonwealth University Undergraduate Bulletin [2015], Virginia Commonwealth University

VCU Bulletins

Undergraduate bulletin for Virginia Commonwealth University for the academic year 2015-2016. It includes information on academic regulations, degree requirements, course offerings, faculty, academic calendar, and tuition and expenses for undergraduate programs.

Virginia Commonwealth University Graduate Bulletin [2015], Virginia Commonwealth University

VCU Bulletins

No abstract provided.

Children's Experiences Of Companion Animal Maltreatment In Households Characterized By Intimate Partner Violence, Shelby Elaine Mcdonald, Elizabeth A. Collins, Nicole Nicotera, Tina O. Hageman, Frank R. Ascione, James Herbert Williams, Sandra A. Graham-Bermann

Social Work Publications

Cruelty toward companion animals is a well-documented, coercive tactic used by abusive partners to intimidate and control their intimate partners. Experiences of co-occurring violence are common for children living in families with intimate partner violence (IPV) and surveys show that more than half are also exposed to abuse of their pets. Given children's relationships with their pets, witnessing such abuse may be traumatic for them. Yet little is known about the prevalence and significance of this issue for children. The present study examines the experiences of children in families with co-occurring pet abuse and IPV. Using qualitative methods, 58 children …

The Glucagon-Like Peptide-1 Receptor As A Potential Treatment Target In Alcohol Use Disorder: Evidence From Human Genetic Association Studies And A Mouse Model Of Alcohol Dependence, P. Suchankova, J. Yan, M. L. Schwandt, B. L. Stangl, E. C. Caparelli, R. Momenan, E. Jerlhag, J. A. Engel, C. A. Hodgkinson, M. Egli, M. F. Lopez, H. C. Becker, D. Goldman, M. Heilig, V. A. Ramchandani, L. Leggio

Psychiatry Publications

The hormone glucagon-like peptide-1 (GLP-1) regulates appetite and food intake. GLP-1 receptor (GLP-1R) activation also attenuates the reinforcing properties of alcohol in rodents. The present translational study is based on four human genetic association studies and one preclinical study providing data that support the hypothesis that GLP-1R may have a role in the pathophysiology of alcohol use disorder (AUD). Case–control analysis (N=908) was performed on a sample of individuals enrolled in the National Institute on Alcohol Abuse and Alcoholism (NIAAA) intramural research program. The Study of Addiction: Genetics and Environment (SAGE) sample (N=3803) was used for …

Qtc Prolongation In Veterans With Heroin Dependence On Methadone Maintenance Treatment, Sameer Hassamal, Antony Fernandez, Hossein Moradi Rekabdarkolaee, Ananda Pandurangi

Psychiatry Publications

Background:

QTc prolongation and Torsade de Ppointes have been reported in patients on methadone maintenance.

Objectives:

In this study, QTc was compared before and after the veteran (n = 49) was on a stable dosage of methadone for 8.72 ± 4.50 years to treat heroin dependence. Risk factors were correlated with the QTc once the veteran was on a stable dose of methadone. Differences in the clinical risk factors in subgroups of veterans with below and above mean QTc change was compared.

Patients and Methods:

ECG data was obtained from a 12-lead electrocardiogram (pre-methadone and on methadone) on 49 veterans. …

Molecular Signatures Of Major Depression, Na Cai, Simon Chang, Yihan Li, Qiban Li, Jingchu Hu, Jieqin Liang, Li Song, Warren Kretzschmar, Xiangchao Gan, Jerome Nicod, Margarita Rivera, Hong Deng, Bo Du, Keqing Li, Wenhu Sang, Jingfang Gao, Shugui Gao, Baowei Ha, Hung-Yao Ho, Chunmei Hu, Jian Hu, Zhenfei Hu, Guoping Huang, Guoqing Jiang, Tao Jiang, Wei Jin, Gongying Li, Kan Li, Yi Li, Yingrui Li, Youhui Li, Yu-Ting Lin, Lanfen Liu, Tiebang Liu, Ying Liu, Yuan Liu, Yao Lu, Luxian Lv, Huaqing Meng, Puyi Qian, Hong Sang, Jianhua Shen, Jianguo Shi, Jing Sun, Ming Tao, Gang Wang, Guangbiao Wang, Jian Wang, Linmao Wang, Xueyi Wang, Xumei Wang, Huanming Yang, Lijun Yang, Ye Yin, Jinbei Zhang, Kerang Zhang, Ning Sun, Wei Zhang, Xiuqing Zhang, Zhen Zhang, Hui Zhong, Gerome Breen, Jun Wang, Jonathan Marchini, Yiping Chen, Qi Xu, Xun Xu, Richard Mott, Guo-Jen Huang, Kenneth S. Kendler, Jonathan Flint

Psychiatry Publications

Adversity, particularly in early life, can cause illness. Clues to the responsible mechanisms may lie with the discovery of molecular signatures of stress, some of which include alterations to an individual’s somatic genome. Here, using genome sequences from 11,670 women, we observed a highly significant association between a stress-related disease, major depression, and the amount of mtDNA (p = 9.00 × 10−42, odds ratio 1.33 [95% confidence interval [CI] = 1.29–1.37]) and telomere length (p = 2.84 × 10−14, odds ratio 0.85 [95% CI = 0.81–0.89]). While both telomere length and mtDNA amount were associated with adverse life events, conditional …