Digital Commons Network^™

Whole Brain And Brain Regional Coexpression Network Interactions Associated With Predisposition To Alcohol Consumption, Lauren A. Vanderlinden, Laura M. Saba, Katerina Kechris, Michael F. Miles, Paula L. Hoffman, Boris Tabakoff

Study of Biological Complexity Publications

To identify brain transcriptional networks that may predispose an animal to consume alcohol, we used weighted gene coexpression network analysis (WGCNA). Candidate coexpression modules are those with an eigengene expression level that correlates significantly with the level of alcohol consumption across a panel of BXD recombinant inbred mouse strains, and that share a genomic region that regulates the module transcript expression levels (mQTL) with a genomic region that regulates alcohol consumption (bQTL). To address a controversy regarding utility of gene expression profiles from whole brain, vs specific brain regions, as indicators of the relationship of gene expression to phenotype, we …

Intracellular Function Of Interleukin-1 Receptor Antagonist In Ischemic Cardiomyocytes, Elena Vecile, Aldo Dobrina, Fadi N. Salloum, Benjamin W. Van Tassell, Antonella Falcione, Edorado Gustini, Samuele Secchiero, Sergio Crovella, Gianfranco Sinagra, Nicoletta Finato, Martin J. Nicklin, Antonio Abbate

VCU Health Publications

Background

Loss of cardiac myocytes due to apoptosis is a relevant feature of ischemic heart disease. It has been described in infarct and peri-infarct regions of the myocardium in coronary syndromes and in ischemia-linked heart remodeling. Previous studies have provided protection against ischemia-induced cardiomyocyte apoptosis by the anti-inflammatory cytokine interleukin-1 receptor-antagonist (IL-1Ra). Mitochondria triggering of caspases plays a central role in ischemia-induced apoptosis. We examined the production of IL-1Ra in the ischemic heart and, based on dual intra/extracellular function of some other interleukins, we hypothesized that IL-1Ra may also directly inhibit mitochondria-activated caspases and cardiomyocyte apoptosis.

Methodology/Principal Findings

Synthesis of …

Superlinear Increase Of Photoluminescence With Excitation Intensity In Zn-Doped Gan, Michael A. Reshchikov, Anita J. Olsen, Marilyn F. Bishop, Tom Mcmullen

Physics Publications

We have observed a superlinear increase of photoluminescence (PL) intensity in a narrow range of excitation intensities for Zn-doped GaN. The characteristic intensity at which the abrupt increase occurs increases with increasing temperature. This is unlike the usual observations for defects in semiconductors in which the PL intensity increases linearly with excitation intensity, saturating at high intensity because defects become saturated with photogenerated charge carriers. The observed phenomenon is attributed to a redirection of electron and hole flow from nonradiative centers at low excitation intensity to a recombination path via the Zn-Ga acceptor at high excitation intensity. This is the …

Subcutaneous Administration Of D-Luciferin Is An Effective Alternative To Intraperitoneal Injection In Bioluminescence Imaging Of Xenograft Tumors In Nude Mice, Ashraf A. Khalil, Mark J. Jameson, William C. Broaddus, Theodore D. Chung, Sarah E. Golding, Seth M. Dever, Elisabeth Rosenberg, Kristoffer Valerie

Otolaryngology Publications

Currently, intraperitoneal (IP) injection of D-luciferin is the preferred method of providing substrate for bioluminescence imaging (BLI); however it has a failure rate of 3–10% due to accidental intestinal injection. The present study evaluates the quality of BLI after subcutaneous (SC) injection of D-luciferin and demonstrates the effectiveness of SC injection in anatomically disparate tumor models. Mice bearing luciferase-expressing tumors underwent BLI after SC or IP injection of D-luciferin. The average time to maximal luminescence was 6 min (range 5–9 min) after SC injection and 8 min (range 5–8 min) after IP injection. Within 7 minutes of injection, SC and …

Partnering, Edward F. Ansello

Director's Editorials from Age in Action

Collaborative partnering has been a core value of Virginia Center on Aging. Several members are partnering with institutions of higher education, public schools, community businesses, and talented instructors.

On Applications And Limitations Of One-Dimensional Capillarity Formulations For Media With Heterogeneous Wettability, T. M. Bucher, H. Vahedi Tafreshi

Mechanical and Nuclear Engineering Publications

Force-balance-based one-dimensional algebraic formulations that are often used in characterizing the capillarity of a multi-component system (e.g., predicting capillary height rise inporous media) are discussed. It is shown that such formulations fail to provide accurate predictions when the distribution of wetting (or non-wetting) surfaces is not homogeneous. A more general mathematical formulation is suggested and used to demonstrate that for media with heterogeneous wettability, hydrophilic (or hydrophobic) surfaces clustered in groups will have less contribution to the overall capillarity of the system.

Genetic, Maternal And Placental Factors In The Association Between Birth Weight And Physical Fitness: A Longitudinal Twin Study, Robert N. H. Touwaslagar, Marji Gielen, Grans E. S. Tan, Antonius L. M. Mulder, Williem J. M. Gerver, Luc J. Zimmermann, Alfons J. H. M. Houben, Maurice P. Zeegers, Catherine Derom, Robert Vlietinck, Hermine Maes, Coen D. A. Stehouwer, Martine Thomis

Human and Molecular Genetics Publications

Background

Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design

Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey.

Results

We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, …

Increased Frequency Of Micronuclei In Adults With A History Of Childhood Sexual Abuse: A Discordant Monozygotic Twin Study, Timothy P. York, Jenni Brumelle, Jane Juusola, Kenneth S. Kendler, Lindon J. Eaves, Ananda B. Amstadler, Steven H. Aggen, Kimberly H. Jones, Andrea Ferreira-Gonzalez, Colleen Jackson-Cook

Human and Molecular Genetics Publications

Background

Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.

Methods

Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a …

The Role Of Tumor-Associated Macrophages In Tumor Vascularization, Chunqing Guo, Annicole Buranych, Devanand Sarkar, Paul B. Fisher, Xiang-Yang Wang

Human and Molecular Genetics Publications

Tumor vascularization is a highly complex process that involves the interaction between tumors and their surrounding stroma, as well as many distinct angiogenesis-regulating factors. Tumor associated macrophages (TAMs) represent one of the most abundant cell components in the tumor environment and key contributors to cancer-related inflammation. A large body of evidence supports the notion that TAMs play a critical role in promoting the formation of an abnormal tumor vascular network and subsequent tumor progression and invasion. Clinical and experimental evidence has shown that high levels of infiltrating TAMs are associated with poor patient prognosis and tumor resistance to therapies. In …

Identification Of Genes Potentially Regulated By Human Polynucleotide Phosphorylase (Hpnpaseold-35) Using Melanoma As A Model, Upneet K. Sokhi, Manny D. Bacolod, Santanu Dasgupta, Luni Emdad, Swadesh K. Das

Human and Molecular Genetics Publications

Human Polynucleotide Phosphorylase (hPNPaseold-35 or PNPT1) is an evolutionarily conserved 3′→5′ exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPaseold-35 in cellular physiology, we knocked-down and overexpressed hPNPaseold-35 in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPaseold-35 resulted in significant …

The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, Aditi R. Chiplunkar, Benjamin C. Curtis, Gabriel L. Eades, Megan S. Kane, Sean J. Fox, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.

Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single …

Krüppel-Like Factor 2 Is Required For Normal Mouse Cardiac Development, Aditi R. Chiplunkar, Tina K. Lung, Yousef Alhashem, Benjamin A. Koppenhaver, Fadi N. Salloum, Rakesh C. Kukreja, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2−/− embryos die earlier, by E11.5. E9.5 FVB/N KLF2−/− hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Targeted Apoptotic Effects Of Thymoquinone And Tamoxifen On Xiap Mediated Akt Regulation In Breast Cancer, Shashi Rajput, B. N. P. Kumar, Siddik Sarkar, Subhasis Das, Belal Azab, Prasanna K. Santhekadur, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher, Mahitosh Mandal

Human and Molecular Genetics Publications

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. …

Amelogenin Peptide Extract Increases Differentiation And Angiogenic And Local Factor Production And Inhibits Apoptosis In Human Osteoblasts, Rene Olivares-Navarrete, Sharon L. Hyzy, Argelia Almaguer-Flores, Corinna Mauth, Anja C. Gemperli, Barbara D. Boyan, Zvi Schwartz

Biomedical Engineering Publications

Enamel matrix derivative (EMD), a decellularized porcine extracellular matrix (ECM), is used clinically in periodontal tissue regeneration. Amelogenin, EMD’s principal component, spontaneously assembles into nanospheres in vivo, forming an ECM complex that releases proteolytically cleaved peptides. However, the role of amelogenin or amelogenin peptides in mediating osteoblast response to EMD is not clear. Human MG63 osteoblast-like cells or normal human osteoblasts were treated with recombinant human amelogenin or a 5 kDa tyrosine-rich amelogenin peptide (TRAP) isolated from EMD and the effect on osteogenesis, local factor production, and apoptosis assessed. Treated MG63 cells increased alkaline phosphatase specific activity and levels of …

Compression Of Multilayered Composite Electrospun Scaffolds: A Novel Strategy To Rapidly Enhance Mechanical Properties And Three Dimensionality Of Bone Scaffolds, Parthasarathy A. Madurantakam, Isaac A. Rodriguez, Koyal Garg, Jennifer M. Mccool, Peter C. Moon, Gary L. Bowlin

Biomedical Engineering Publications

One major limitation of electrospun scaffolds intended for bone tissue engineering is their inferior mechanical properties. The present study introduces a novel strategy to engineer stiffer scaffolds by stacking multiple layers and cold welding them under high pressure. Electrospun polydioxanone (PDO) and PDO:nanohydroxyapatite (PDO:nHA) scaffolds (1, 2, or 4 layered stacks) were compressed either before or after mineralizing treatment with simulated body fluid (SBF). After two weeks in SBF, scaffolds were analyzed for total mineral content and stiffness by Alizarin red S and uniaxial tensile testing, respectively. Scaffolds were also analyzed for permeability, pore size, and fiber diameter. Results indicated …

Correlation Between Si Doping And Stacking Fault Related Luminescence In Homoepitaxial M-Plane Gan, S. Khromov, B. Monemar, Vitaliy Avrutin, Hadis Morkoç, L. Hultman, G. Pozina

Electrical and Computer Engineering Publications

Si-doped GaN layers grown by metal organic vapor phase epitaxy on m-plane GaN substrates were investigated by low-temperature cathodoluminescence (CL). We have observed stacking fault (SF) related emission in the range of 3.29–3.42 eV for samples with moderate doping, while for the layers with high concentration of dopants, no CL lines related to SFs have been noted. Perturbation of the SF potential profile by neighboring impurity atoms can explain localization ofexcitons at SFs, while this effect would vanish at high doping levels due to screening.

Cam Use Among Overweight And Obese Persons With Radiographic Knee Osteoarthritis, Kate L. Lapane, Shibing Yang, Rachel Jawahar, Timothy Mcalindon, Charles B. Eaton

Family Medicine and Population Health Publications

Background

Obesity is associated with knee pain and is an independent predictor of incident knee osteoarthritis (OA); increased pain with movement often leads patients to adopt sedentary lifestyles to avoid pain. Detailed descriptions of pain management strategies by body mass index (BMI) level among OA patients are lacking. The objectives were to describe complementary and alternative medicine (CAM) and conventional medication use by BMI level and identify correlates of CAM use by BMI level.

Methods

Using Osteoarthritis Initiative baseline data, 2,675 patients with radiographic tibiofemoral OA in at least one knee were identified. Use of CAM therapies and conventional medications …

Association Between Adverse Childhood Experiences And Diagnosis Of Cancer, Monique J. Brown, Leroy R. Thacker, Steven A. Cohen

Family Medicine and Population Health Publications

Objective

Adverse childhood experiences (ACEs) are linked to multiple adverse health outcomes. This study examined the association between ACEs and cancer diagnosis.

Methods

Data from the 2010 Behavioral Risk Factor Surveillance System (BRFSS) survey were used. The BRFSS is the largest ongoing telephone health survey, conducted in all US states, the District of Columbia, Puerto Rico, Guam and the U.S. Virgin Islands, and provides data on a variety of health issues among the non-institutionalized adult population. Principal component analysis (PCA) was used to derive components for ACEs. Multivariable logistic regression models were used to provide adjusted odds ratios (OR) and …

Pre-Pregnancy Bmi And Weight Gain: Where Is The Tipping Point For Preterm Birth?, Saba W. Masho, Diane Bishop, Meaghan Munn

Family Medicine and Population Health Publications

Background

Obesity in pregnant women is a major problem affecting both the mother and her offspring. Literature on the effect of obesity on preterm birth is inconsistent and few studies have investigated the influence of weight gain during pregnancy. This study examined the effect of maternal pre-pregnancy BMI and weight gain during pregnancy on preterm birth.

Methods

Data from the Collaborative Perinatal Project (CPP) on 45,824 pregnant women with singleton, live-born infants with no severe congenital anomalies was analyzed. Primary outcome variables included preterm (< 37 weeks of gestation), categorized into spontaneous preterm with and without premature rupture of membrane (PROM) and indicated preterm. Maternal BMI was categorized into underweight (BMI < 18.50), normal weight (BMI =1 8.50 – 24.99), overweight (BMI = 25.00 – 29.99), and obese (BMI ≥ 30.00). Multinomial regression analysis was conducted and OR and 95% CI were calculated.

Results

The rate of spontaneous preterm birth with PROM among overweight women decreased with increasing …

Fyn Kinase Is Required For Optimal Humoral Responses, Natalia S. Chaimowitz, Yves T. Falanga, John J. Ryan, Daniel H. Conrad

Microbiology and Immunology Publications

Abstract

The generation of antigen-specific antibodies and the development of immunological memory require collaboration between B and T cells. T cell-secreted IL-4 is important for B cell survival, isotype switch to IgG1 and IgE, affinity maturation, and the development of germinal centers (GC). Fyn, a member of the Src family tyrosine kinase, is widely expressed in many cell types, including lymphocytes. This kinase is known to interact with both the B cell and T cell receptor (BCR and TCR, respectively). While Fyn deletion does not impair the development of immature T cells and B cells, TCR signaling is altered in …

Hiv Protease Inhibitors Disrupt Lipid Metabolism By Activating Endoplasmic Reticulum Stress And Inhibiting Autophagy Activity In Adipocytes, Beth S. Zha, Xiaoshan Wan, Xiaoxuan Zhang, Weibin Zha, Jun Zhou, Martin Wabitsch, Guangji Wang, Vijay Lyall, Phillip B. Hylemon, Huiping Zhou

Microbiology and Immunology Publications

Background

HIV protease inhibitors (PI) are core components of Highly Active Antiretroviral Therapy (HAART), the most effective treatment for HIV infection currently available. However, HIV PIs have now been linked to lipodystrophy and dyslipidemia, which are major risk factors for cardiovascular disease and metabolic syndrome. Our previous studies have shown that HIV PIs activate endoplasmic reticulum (ER) stress and disrupt lipid metabolism in hepatocytes and macrophages. Yet, little is known on how HIV PIs disrupt lipid metabolism in adipocytes, a major cell type involved in the pathogenesis of metabolic syndrome.

Methodology and Principal Findings

Cultured and primary mouse adipocytes and …

Inhibition Of P-Glycoprotein By Hiv Protease Inhibitors Increases Intracellular Accumulation Of Berberine In Murine And Human Macrophages, Weibin Zha, Guangji Wang, Weiren Xu, Xuyuan Liu, Yun Wang, Beth S. Zha, Jian Shi, Qijin Zhao, Phillip M. Gerk, Elaine Studer, Phillip B. Hylemon, William M. Pandak Jr., Huiping Zhou

Microbiology and Immunology Publications

Background

HIV protease inhibitor (PI)-induced inflammatory response in macrophages is a major risk factor for cardiovascular diseases. We have previously reported that berberine (BBR), a traditional herbal medicine, prevents HIV PI-induced inflammatory response through inhibiting endoplasmic reticulum (ER) stress in macrophages. We also found that HIV PIs significantly increased the intracellular concentrations of BBR in macrophages. However, the underlying mechanisms of HIV PI-induced BBR accumulation are unknown. This study examined the role of P-glycoprotein (P-gp) in HIV PI-mediated accumulation of BBR in macrophages.

Methodology and Principal Findings

Cultured mouse RAW264.7 macrophages, human THP-1-derived macrophages, Wild type MDCK (MDCK/WT) and human …

Virginia Commonwealth University Fall Commencement Program [Corrected Copy] [2013], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Menorah Review (No. 79, Summer/Fall, 2013)

Menorah Review

Authorities Without Power: The Jewish Council of Vienna During the Holocaust -- Books in Brief: New and Notable -- Cry and Wail: Jewish Suffering in Documents From Ukraine, 1918-1921 -- Moreshet: From the Sources -- Speaking of the Law -- The Jewish "Success" Story? -- The Power of the Word -- Two Poems by Richard Sherwin -- Unearthing Buried Treasures: Reading Leah Goldberg in Translation

Virginia Commonwealth University Undergraduate Bulletin Courses [2013], Virginia Commonwealth University

VCU Bulletins

Listing of undergraduate courses for 2013-2014.

Biological Characterization Of 3-(2-Amino-Ethyl)-5-[3-(4-Butoxyl-Phenyl)-Propylidene]-Thiazolidine-2,4-Dione (K145) As A Selective Sphingosine Kinase-2 Inhibitor And Anticancer Agent, Kai Liu, Tai L. Guo, Nitai C. Hait, Jeremy Allegood, Hardik I. Parikh, Wenfang Xu, Glen E. Kellogg, Steven Grant, Sarah Spiegel, Shijun Zhang

Medicinal Chemistry Publications

In our effort to develop selective sphingosine kinase-2 (SphK2) inhibitors as pharmacological tools, a thiazolidine-2,4-dione analogue, 3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione(K145), was synthesized and biologically characterized. Biochemical assay results indicate that K145 is a selective SphK2 inhibitor. Molecular modeling studies also support this notion. In vitro studies using human leukemia U937 cells demonstrated that K145 accumulates in U937 cells, suppresses the S1P level, and inhibits SphK2. K145 also exhibited inhibitory effects on the growth of U937 cells as well as apoptotic effects in U937 cells, and that these effects may be through the inhibition of down-stream ERK and Akt signaling pathways. K145 also significantly …

Predicting Dyspnea Inducers By Molecular Topology, María Gálvez-Llompart,, Jorge Gálvez, Ramón García-Domenech, Lemont B. Kier

Study of Biological Complexity Publications

QSAR based on molecular topology (MT) is an excellent methodology used in predicting physicochemical and biological properties of compounds. This approach is applied here for the development of a mathematical model capable to recognize drugs showing dyspnea as a side effect. Using linear discriminant analysis, it was found a four-variable regression equations enabling a predictive rate of about 81% and 73% in the training and test sets of compounds, respectively. These results demonstrate that QSAR-MT is an efficient tool to predict the appearance of dyspnea associated with drug consumption.

The Influence Of Hypoxia And Ph On Bioluminescence Imaging Of Luciferase-Transfected Tumor Cells And Xenografts, Ashraf A. Khalil, Mark J. Jameson, William C. Broaddus, Peck Sun Lin, Seth M. Dever, Sarah E. Golding, Elisabeth Rosenberg, Kristoffer Valerie, Theodore D. Chung

Neurosurgery Publications

Bioluminescence imaging (BLI) is a relatively new noninvasive technology used for quantitative assessment of tumor growth and therapeutic effect in living animal models. BLI involves the generation of light by luciferase-expressing cells following administration of the substrate luciferin in the presence of oxygen and ATP. In the present study, the effects of hypoxia, hypoperfusion, and pH on BLI signal (BLS) intensity were evaluated in vitro using cultured cells and in vivo using a xenograft model in nude mice. The intensity of the BLS was significantly reduced in the presence of acute and chronic hypoxia. Changes in cell density, viability, and …

Virginia Commonwealth University Fall Commencement Program [2013], Virginia Commonwealth University

VCU Commencement Programs

No abstract provided.

Dynamics At A Janus Interface, M. Von Domaros, D. Bratko, B. Kirchner, A. Luzar

Chemistry Publications

Electric field effects on water interfacial properties abound, ranging from electrochemical cells to nanofluidic devices to membrane ion channels. On the nanoscale, spontaneous orientational polarization of water couples with field alignment, resulting in an asymmetric wetting behavior of opposing surfacesa field-induced analogue of a chemically generated Janus interface. Using atomistic simulations, we uncover a new and significant field polarity (sign) dependence of the dipolar- orientation polarization dynamics in the hydration layer. Applying electric fields across a nanoparticle, or a nanopore, can lead to close to 2 orders of magnitude difference in response times of water polarization at opposite surfaces. Typical …