Digital Commons Network^™

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 …

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 …

Virginia Commonwealth University Courses [2015], Virginia Commonwealth University

VCU Bulletins

Listing of courses for the 2015-2016 academic year.

Decellularization Of Porcine Lung Tissue, Kirsten Hulbert, Linh Ta, Lumumba Reid, Mahir Dagra, Baltej Dhillon

Capstone Design Expo Posters

Our project aims to standardize the decellularization of a porcine lung by creating a bioreactor to house the lung, automating the decellularization process and developing a protocol that will increase the precision and the repeatability of the process. Our deliverables include a working prototype, an automated system that will inform the user when the decellularization process is complete, a pressure sensor to control perfusion, and automated pressurized pulses that will increase the rate of decellularization.

Our accomplishments thus far include: a design for a working prototype that will decellularize a porcine lung, determining the proper rate to perfuse the lung, …

Black Creek Baptist Church, Megan Mantlo

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.

Hindu Center Of Virginia, Daija Resurreccion

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.

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 …

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 …

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 …

Dpy-17 And Mua-3 Interact For Connective Tissue-Like Tissue Integrity In Caenorhabditis Elegans: A Model For Marfan Syndrome, Pauline Fotopoulos, Jeongho Kim, Moonjung Hyun, Waiss Qamari, Inhwan Lee, Young-Jai You

Biochemistry and Molecular Biology Publications

mua-3 is a Caenorhabditis elegans homolog of the mammalian fibrillin1, a monogenic cause of Marfan syndrome. We identified a new mutation of mua-3that carries an in-frame deletion of 131 amino acids in the extracellular domain, which allows the mutants to survive in a temperature-dependent manner; at the permissive temperature, the mutants grow normally without obvious phenotypes, but at the nonpermissive temperature, more than 90% die during the L4 molt due to internal organ detachment. Using the temperature-sensitive lethality, we performed unbiased genetic screens to isolate suppressors to find genetic interactors of MUA-3. From two independent screens, we isolated …

The Phosphorylated Prodrug Fty720 Is A Histone Deacetylase Inhibitor That Reactivates Erα Expression And Enhances Hormonal Therapy For Breast Cancer, Nitai C. Hait, Dorit Avni, Akimitsu Yamada, Masayuki Nagahashi, Tomoyoshi Aoyagi, Hiroaki Aoki, Catherine I. Dumur, Z Zelenko, E J. Gallagher, D Leroith, Sheldon Milstien, Kazuaki Takabe, Sarah Spiegel

Biochemistry and Molecular Biology Publications

Estrogen receptor-α (ERα)-negative breast cancer is clinically aggressive and does not respond to conventional hormonal therapies. Strategies that lead to re-expression of ERα could sensitize ERα-negative breast cancers to selective ER modulators. FTY720 (fingolimod, Gilenya), a sphingosine analog, is the Food and Drug Administration (FDA)-approved prodrug for treatment of multiple sclerosis that also has anticancer actions that are not yet well understood. We found that FTY720 is phosphorylated in breast cancer cells by nuclear sphingosine kinase 2 and accumulates there. Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of …

Understanding Host-Switching By Ecological Fitting, Sabrina B. L. Araujo, Mariana Pires Braga, Daniel R. Brooks, Salvatore J. Agosta, Eric P. Hoberg, Francisco W. Von Hartenthal, Walter A. Boeger

Biology Publications

Despite the fact that parasites are highly specialized with respect to their hosts, empirical evidence demonstrates that host switching rather than co-speciation is the dominant factor influencing the diversification of host-parasite associations. Ecological fitting in sloppy fitness space has been proposed as a mechanism allowing ecological specialists to host-switch readily. That proposal is tested herein using an individual-based model of host switching. The model considers a parasite species exposed to multiple host resources. Through time host range expansion can occur readily without the prior evolution of novel genetic capacities. It also produces non-linear variation in the size of the fitness …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin J. C. G. Van Den Oord

Biomarker Research and Personalized Medicine Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …

High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia And Renal Failure In Nephrectomized Ldl Receptor Knockout Mice: Role Of Intestine Derived Lipopolysaccharide, Siddhartha S. Ghosh, Samuel Righi, Richard Krieg, Le Kang, Daniel Carl, Jing Wang, H. Davis Massey, Domenic A. Sica, Todd W. B. Gehr, Shobha Ghosh

Anatomy and Neurobiology Publications

A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham …

Elucidating The Role Of Injury-Induced Electric Fields (Efs) In Regulating The Astrocytic Response To Injury In The Mammalian Central Nervous System, Matthew L. Baer, Scott C. Henderson, Raymond J. Colello

Anatomy and Neurobiology Publications

Injury to the vertebrate central nervous system (CNS) induces astrocytes to change their morphology, to increase their rate of proliferation, and to display directional migration to the injury site, all to facilitate repair. These astrocytic responses to injury occur in a clear temporal sequence and, by their intensity and duration, can have both beneficial and detrimental effects on the repair of damaged CNS tissue. Studies on highly regenerative tissues in non-mammalian vertebrates have demonstrated that the intensity of direct-current extracellular electric fields (EFs) at the injury site, which are 50–100 fold greater than in uninjured tissue, represent a potent signal …

Menorah Review (No. 83, Summer/Fall, 2015)

Menorah Review

L’hitraot... -- A Model of Courage -- Books in Brief -- Compassion and Truth Meet (Psalm 85.11) -- Four Poems -- From the Classics -- Judaism and a Heliocentric Universe -- Two Essays by Peter Haas -- Zachor

Γ-Secretase Inhibitor Alleviates Acute Airway Inflammation Of Allergic Asthma In Mice By Downregulating Th17 Cell Differentiation, Weixi Zhang, Xueya Zhang, Anqun Sheng, Cuiye Weng, Tingting Zhu, Wei Zhao, Changchong Li

Pediatrics Publications

T helper 17 (Th17) cells play an important role in the pathogenesis of allergic asthma. Th17 cell differentiation requires Notch signaling. γ-Secretase inhibitor (GSI) blocks Notch signaling; thus, it may be considered as a potential treatment for allergic asthma. The aim of this study was to evaluate the effect of GSI on Th17 cell differentiation in a mouse model of allergic asthma. OVA was used to induce mouse asthma model in the presence and absence of GSI. GSI ameliorated the development of OVA-induced asthma, including suppressing airway inflammation responses and reducing the severity of clinical signs. GSI also significantly …

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

Medicinal Chemistry 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 …

Liver X Receptor-Dependent Inhibition Of Microglial Nitric Oxide Synthase 2, Julie R Secor Mcvoy, Hanadi Ajam Oughli, Unsong Oh

Neurology Publications

Background

The nuclear receptor liver X receptor (LXR) exerts transcriptional control over lipid metabolism and inflammatory response in cells of the myeloid lineage, suggesting that LXR may be a potential target in a number of chronic neuroinflammatory and neurodegenerative diseases where persistent microglial activation has been implicated in the pathogenesis.

Methods

The effect of LXR activation on microglia and central nervous system (CNS) inflammation was studied using a synthetic LXR agonist in cultured microglia, a microglial cell line and experimental allergic encephalomyelitis (EAE), an animal model of CNS inflammation.

Results

LXR activation inhibited nitric oxide synthase 2, inducible (Nos2 …

Risk Assessment Based On Indirect Predation Cues: Revisiting Fine-Grained Variation, Michael W. Mccoy, Stefan K. Wheat, Karen M. Warkentin, James R. Vonesh

Biology Publications

To adaptively express inducible defenses, prey must gauge risk based on indirect cues of predation. However, the information contained in indirect cues that enable prey to fine-tune their phenotypes to variation in risk is still unclear. In aquatic systems, research has focused on cue concentration as the key variable driving threat-sensitive responses to risk. However, while risk is measured as individuals killed per time, cue concentration may vary with either the number or biomass killed. Alternatively, fine-grained variation in cue, that is, frequency of cue pulses irrespective of concentration, may provide a more reliable signal of risk. Here, we present …

Interrogating The Venom Of The Viperid Snake Sistrurus Catenatus Edwardsii By A Combined Approach Of Electrospray And Maldi Mass Spectrometry, Alex Chapeaurouge, Md Abu Reza, Stephen P. Mackessy, Paulo C. Carvalho, Richard H. Valente, André Teixeira-Ferreira, Jonas Perales, Qingsong Lin, R. Manjunatha Kini

Biochemistry and Molecular Biology Publications

The complete sequence characterization of snake venom proteins by mass spectrometry is rather challenging due to the presence of multiple isoforms from different protein families. In the present study, we investigated the tryptic digest of the venom of the viperid snake Sistrurus catenatus edwardsii by a combined approach of liquid chromatography coupled to either electrospray (online) or MALDI (offline) mass spectrometry. These different ionization techniques proved to be complementary allowing the identification a great variety of isoforms of diverse snake venom protein families, as evidenced by the detection of the corresponding unique peptides. For example, ten out of eleven predicted …

Consequences Of Life History Switch Point Plasticity For Juvenile Morphology And Locomotion In The Túngara Frog, Julie Charbonnier, James R. Vonesh

Biology Publications

Many animals with complex life cycles can cope with environmental uncertainty by altering the timing of life history switch points through plasticity. Pond hydroperiod has important consequences for the fitness of aquatic organisms and many taxa alter the timing of life history switch points in response to habitat desiccation. For example, larval amphibians can metamorphose early to escape drying ponds. Such plasticity may induce variation in size and morphology of juveniles which can result in carry-over effects on jumping performance. To investigate the carry-over effects of metamorphic plasticity to pond drying, we studied the Túngara frog,Physalaemus pustulosus, a …

Progressive Cognitive Deficit, Motor Impairment And Striatal Pathology In A Transgenic Huntington Disease Monkey Model From Infancy To Adulthood, Anthony W. S. Chan, Jie Jiang, Yiju Chen, Chunxia Li, Melinda S. Prucha, Yijuan Hu, Tim Chi, Sean Moran, Tayeb Rahim, Shihua Li, Xiaojiang Li, Stuart M. Zola, Claudia M. Testa, Hui Mao, Rosa Villalba, Yoland Smith, Xiaodong Zhang, Jocelyne Bachevalier

Neurology Publications

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in …

Virginia Dental Journal (Vol. 92, No. 4, 2015)

Virginia Dental Journal

No abstract provided.

Comparison Of Effectiveness Of Cefovecin, Doxycycline, And Amoxicillin For The Treatment Of Experimentally Induced Early Lyme Borreliosis In Dogs, Bettina Wagner, John Johnson, David Garcia-Tapia, Nicole Honsberger, Vickie King, Catherine Strietzel, John M. Hardham, Thomas J. Heinz, Richard T. Marconi, Patrick F.M. Meeus

Microbiology and Immunology Publications

Background

While Koch’s postulates have been fulfilled for Lyme disease; causing transient fever, anorexia and arthritis in young dogs; treatment of sero-positive dogs, especially asymptomatic animals, remains a topic of debate. To complicate this matter the currently recommended antibiotic treatments of Lyme Disease in dogs caused by Borrelia burgdorferi require daily oral administrations for 31 days or longer, which makes non-compliance a concern. Additionally, there is no approved veterinary antimicrobial for the treatment of Lyme Disease in dogs in the USA and few recommended treatments have been robustly tested.

In vitro testing of cefovecin, a novel extended-spectrum cephalosporin, demonstrated inhibition …

Hindu Center Of Virginia, Janel Boyles De Rondon

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.

Cathedral Of The Sacred Heart, Emilie Urquidi

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.

Behavioral Observations: Foraging And Aggression Of Neotropical Migrants And Resident Birds In Panama, Jessica M. Johnston, Samuel B. King, Ryan A. Levering

Rice Rivers Center Research Symposium

Lyons suggests that foraging data in songbirds can be an indicator of food abundance, with higher attack rate= higher habitat quality; higher foraging speed= lower habitat quality (2005). Territorial behavior such as interspecific aggression among songbirds may also be related to food availability. Previous studies have documented variation in the extent of territorial and aggressive behaviors among resident and Neotropical migratory species on tropical wintering grounds. This research gathered foraging and aggression data at two coastal angroves sites in central Panama, one on the Caribbean Coast (Galeta) and one on the Pacific Coast (Juan Diaz-East). Foraging data was used an …