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Bacterial Artificial Chromosome Clones Of Viruses Comprising The Towne Cytomegalovirus Vaccine, Xiaohong Cui, Stuart P. Adler, Andrew J. Davison, Larry Smith, El-Sayed E. Habib, Michael A. Mcvoy

Pediatrics Publications

Bacterial artificial chromosome (BAC) clones have proven invaluable for genetic manipulation of herpesvirus genomes. BAC cloning can also be useful for capturing representative genomes that comprise a viral stock or mixture. The Towne live attenuated cytomegalovirus vaccine was developed in the 1970s by serial passage in cultured fibroblasts. Although its safety, immunogenicity, and efficacy have been evaluated in nearly a thousand human subjects, the vaccine itself has been little studied. Instead, genetic composition and in vitro growth properties have been inferred from studies of laboratory stocks that may not always accurately represent the viruses that comprise the vaccine. Here we …

Hemorrhage Detection And Segmentation In Traumatic Pelvic Injuries, Pavani Davuluri, Jie Wu, Yang Tang, Charles H. Cockrell, Kevin R. Ward, Kayvan Najarian, Rosalyn H. Hargraves

Electrical and Computer Engineering Publications

Automated hemorrhage detection and segmentation in traumatic pelvic injuries is vital for fast and accurate treatment decision making. Hemorrhage is the main cause of deaths in patients within first 24 hours after the injury. It is very time consuming for physicians to analyze all Computed Tomography (CT) images manually. As time is crucial in emergence medicine, analyzing medical images manually delays the decision-making process. Automated hemorrhage detection and segmentation can significantly help physicians to analyze these images and make fast and accurate decisions. Hemorrhage segmentation is a crucial step in the accurate diagnosis and treatment decision-making process. This paper presents …

A Comparison Of Two Distinct Murine Macrophage Gene Expression Profiles In Response To Leishmania Amazonensis Infection, Christian M. Probst, Rodrigo A. Silva, Juliana P.B. Menezes, Tais F. Almeida, Ivana N. Gomes, Andréia C. Dallabona, Luiz S. Ozaki, Gregory A. Buck, Daniel P. Pavoni, Marco A. Krieger, Patrícia S.T. Veras

Study of Biological Complexity Publications

Background

The experimental murine model of leishmaniasis has been widely used to characterize the immune response against Leishmania. CBA mice develop severe lesions, while C57BL/6 present small chronic lesions under L. amazonensis infection. Employing a transcriptomic approach combined with biological network analysis, the gene expression profiles of C57BL/6 and CBA macrophages, before and after L. amazonensis infection in vitro, were compared. These strains were selected due to their different degrees of susceptibility to this parasite.

Results

The genes expressed by C57BL/6 and CBA macrophages, before and after infection, differ greatly, both with respect to absolute number as well as …

Genome-Wide Association Study Heterogeneous Cohort Homogenization Via Subject Weight Knock-Down, Andre X. C. N. Valente, Joseph Zischkau, Joo H. Shin, Yuan Gao, Abhijit Sarkar

Study of Biological Complexity Publications

Population structure can be a source of both false-positive and false-negative findings in a genome-wide association study. This article proposes an approach that helps to reduce the false-positives. It consists of homogenizing the diseased/healthy phenotype ratio across the cohort, by decreasing the statistical weight of selected individuals. After homogenization, the cohort is statistically handled as if originating from a single well-mixed population. The method was applied to homogenize a Parkinson's disease genome-wide association study cohort.

Nordp News 2.2, National Organization Of Research Development Professionals, Jeffrey M. Anderson (Ed.)

Research Development Repository

This is an upload of a past issue of the NORDP News Newsletter. The table of contents includes:

• New ERA of Transatlantic Research Collaborations

• President’s Corner

• Stay out of the Hazards: What do NIH and Golf have in Common?

• Social Scientists and Research Development

• What to Say—and Not Say—to Program Officers

• Upcoming Research Development Conferences

• Research Development Jobs Sampler

Pcr Detection Of Malaria Parasites In Desiccated Anopheles Mosquitoes Is Uninhibited By Storage Time And Temperature, Mark A. Rider, Brian D. Byrd, Joseph Keating, Dawn M. Wesson, Kevin A. Caillouet

Biostatistics Publications

Background

Reliable methods to preserve mosquito vectors for malaria studies are necessary for detectingPlasmodium parasites. In field settings, however, maintaining a cold chain of storage from the time of collection until laboratory processing, or accessing other reliable means of sample preservation is often logistically impractical or cost prohibitive. As the Plasmodium infection rate of Anophelesmosquitoes is a central component of the entomological inoculation rate and other indicators of transmission intensity, storage conditions that affect pathogen detection may bias malaria surveillance indicators. This study investigated the effect of storage time and temperature on the ability to detect Plasmodium parasites …

Alternatives To Mixture Model Analysis Of Correlated Binomial Data, N. Rao Chaganty, Roy Sabo, Yihao Deng

Biostatistics Publications

While univariate instances of binomial data are readily handled with generalized linear models, cases of multivariate or repeated measure binomial data are complicated by the possibility of correlated responses. Likelihood-based estimation can be applied by using mixture distribution models, though this approach can present computational challenges. The logistic transformation can be used to bypass these concerns and allow for alternative estimating procedures. One popular alternative is the generalized estimating equation (GEE) method, though systematic errors can lead to infeasible correlation estimates or nonconvergence problems. Our approach is the coupling of quasileast squares (QLSs) method with a rarely used matrix factorization, …

Reduced Expression Of Inflammatory Genes In Deceased Donor Kidneys Undergoing Pulsatile Pump Preservation, Valeria Mas, Kellie J. Archer, Catherine I. Dumur, Mariano J. Scian, Jihee L. Suh, Anne L. King, Megan E. Wardius, Julie A. Straub, Marc P. Posner, Kenneth Brayman, Daniel Maluf

Biostatistics Publications

Background

The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys.

Methodology/Principal Findings

99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24–62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/−509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/−485 minutes) (P

Conclusions/Significance …

Molecular Profiles Of Hcv Cirrhotic Tissues Derived In A Panel Of Markers With Clinical Utility For Hepatocellular Carcinoma Surveillance, Ricardo Gehrau, Kellie Archer, Valeria Mas, Daniel Maluf

Biostatistics Publications

Background

Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome-wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures.

Methodology/Principal Findings

Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR<1% was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction model included 17 molecules demonstrated 98.6% of accuracy and correctly classified 6 out of 11 undiagnosed iHCC cases. The best model performed even better in the additional independent set.

Conclusions/Significances

The …

Biomarkers Of Disease Differentiation: Hcv Recurrence Versus Acute Cellular Rejection, Ricardo Gehrau, Valeria Mas, Kellie Archer, Daniel Maluf

Biostatistics Publications

The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis …

Virginia Dental Journal (Vol. 89, No. 2, 2012)

Virginia Dental Journal

No abstract provided.

Interaction Between Mu And Delta Opioid Receptor Agonists In An Assay Of Capsaicin-Induced Thermal Allodynia In Rhesus Monkeys, S. Stevens Negus, Ember Morrissey, John E. Folk, Kenner C. Rice

Pharmacology and Toxicology Publications

Delta opioid agonists enhance antinociceptive effects of mu-opioid agonists in many preclinical assays of acute nociception, but delta/mu interactions in preclinical models of inflammation-associated pain have not been examined. This study examined interactions between the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and the mu agonist analgesics methadone, morphine, and nalbuphine in an assay of capsaicin-induced thermal allodynia in rhesus monkeys. Thermal allodynia was produced by topical application of capsaicin to the tail. Antiallodynic effects of methadone, morphine, and nalbuphine were evaluated alone or in combination with fixed proportions of SNC80 identical to proportions previously shown to enhance acute thermal antinociceptive effects of …

Mdan-21: A Bivalent Opioid Ligand Containing Mu-Agonist And Delta-Antagonist Pharmacophores And Its Effects In Rhesus Monkeys, Mario D. Aceto, Louis S. Harris, S. Stevens Negus, Matthew L. Banks, Larry D. Hughes, Eyup Akgun, Philip S. Portoghese

Pharmacology and Toxicology Publications

MDAN-21, , a bivalent opioid ligand containing a mu-opioid receptor agonist (derived from oxymorphone) linked to the delta-opioid receptor antagonist (related to naltrindole) by a spacer of 21 atoms, was reported to have potent analgesic properties in mice. Tolerance, physical dependence, and conditioned place preference were not evident in that species. The finding that bivalent ligands in this series, with spacers 19 atoms or greater, were devoid of tolerance and dependence led to the proposal that MDAN-21 targets heteromeric mu-delta-opioid receptors. The present study focused on its effects in nonhuman primates (Macaca mulatta), a species with a physiology and behavioral …

Acid Sphingomyelinase Gene Knockout Ameliorates Hyperhomocysteinemic Glomerular Injury In Mice Lacking Cystathionine-Β-Synthase, Krishna M. Boini, Min Xia, Justine M. Abais, Ming Xu, Cai-Xia Li, Pin-Lan Li

Pharmacology and Toxicology Publications

Acid sphingomyelinase (ASM) has been implicated in the development of hyperhomocysteinemia (hHcys)-induced glomerular oxidative stress and injury. However, it remains unknown whether genetically engineering of ASM gene produces beneficial or detrimental action on hHcys-induced glomerular injury. The present study generated and characterized the mice lacking cystathionine β-synthase (Cbs) and Asm mouse gene by cross breeding Cbs+/− and Asm+/− mice. Given that the homozygotes of Cbs−/−/Asm−/− mice could not survive for 3 weeks. Cbs+/−/Asm+/+, Cbs+/−/Asm+/− and Cbs+/−/Asm−/− as well as their Cbs wild type littermates were used to study the role of Asm−/− under a background of Cbs+/− with hHcys. HPLC …

Free Your Mind: Contemporary Racial Attitudes And Post Racial Theory, Lakeyta M. Bonnette, Sarah M. Gershon, Precious D. Hall

Ethnic Studies Review

The inauguration of the United States first Black President has prompted mass discussions of race relations in America. It is often articulated that America is now in a post-racial society. However, the question still remains: does the election of a Black president demonstrate that America is now a "color-blind" society? To answer this question, we rely on data collected by PEW (2007). Our results suggest that white and African Americans differ significantly in the extent to which they express post-racial attitudes. Specifically, we find that whites more commonly express post-racial attitudes, claiming that racism and discrimination are rare, in opposition …

Predicting Protein Interactions By Brownian Dynamics Simulations, Xuan-Yu Meng, Yu Xu, Hong Zhang, Mihaly Mezei, Meng Cui

Physiology and Biophysics Publications and Presentations

We present a newly adapted Brownian-Dynamics (BD)-based protein docking method for predicting native protein complexes. The approach includes global BD conformational sampling, compact complex selection, and local energy minimization. In order to reduce the computational costs for energy evaluations, a shell-based grid force field was developed to represent the receptor protein and solvation effects. The performance of this BD protein docking approach has been evaluated on a test set of 24 crystal protein complexes. Reproduction of experimental structures in the test set indicates the adequate conformational sampling and accurate scoring of this BD protein docking approach. Furthermore, we have developed …

The Molecular Mechanism By Which Pip2 Opens The Intracellular G-Loop Gate Of A Kir3.1 Channel, Xuan-Yu Meng, Hong-Xing Zhang, Diomedes E. Logothetis, Meng Cui

Physiology and Biophysics Publications and Presentations

Abstract

Inwardly rectifying potassium (Kir) channels are characterized by a long pore comprised of continuous transmembrane and cytosolic portions. A high-resolution structure of a Kir3.1 chimera revealed the presence of the cytosolic (G-loop) gate captured in the closed or open conformations. Here, we conducted molecular-dynamics simulations of these two channel states in the presence and absence of phosphatidylinositol bisphosphate (PIP₂), a phospholipid that is known to gate Kir channels. Simulations of the closed state with PIP₂ revealed an intermediate state between the closed and open conformations involving direct transient interactions with PIP₂, as well as …

Normal-Mode-Analysis-Guided Investigation Of Crucial Intersubunit Contacts In The Camp-Dependent Gating In Hcn Channels, Farzana Marni, Shengjun Wu, Gaurav M. Shah, Xin-Ping Xu, Amber R. Hackett, Changan Xie, Sabisha Shrestha, Lin Liu, Qinglian Liu, Lei Zhou

Physiology and Biophysics Publications and Presentations

Abstract

Protein structures define a complex network of atomic interactions in three dimensions. Direct visualization of the structure and analysis of the interaction potential energy are not straightforward approaches to pinpoint the atomic contacts that are crucial for protein function. We used the tetrameric hyperpolarization-activated cAMP-regulated (HCN) channel as a model system to study the intersubunit contacts in cAMP-dependent gating. To obtain a systematic survey of the contacts between each pair of residues, we used normal-mode analysis, a computational approach for studying protein dynamics, and constructed the covariance matrix for C-α atoms. The significant contacts revealed by covariance analysis …

Profiles In Science: John Bennett Fenn, Kimberly Brady, Roy Brown, Emily Johnson, Shannon D. Jones, Margaret Henderson, Dana Ladd, Irene Lubker, Jennifer A. Mcdaniel

VCU Libraries Faculty and Staff Publications

“Don’t ever try to be a scientist or engineer!” Had John Bennett Fenn listened to this advice given by his ninth grade teacher, he might not have gone on to pursue a career in analytical chemistry which would culminate in the attainment of the Nobel Prize in 2002. Gathered from interviews, publication analyses, glowing tributes, and his reminiscences, this paper outlines the academic and professional life of John Fenn from childhood through the end of his career in 2010.

A Blue Native-Page Analysis Of Membrane Protein Complexes In Clostridium Thermocellum, Yanfeng Peng, Yuanming Luo, Tingting Yu, Xinping Xu, Keqiang Fan, Youbao Zhao, Kequian Yang

Physiology and Biophysics Publications and Presentations

Background Clostridium thermocellum is a Gram-positive thermophilic anaerobic bacterium with the unusual capacity to convert cellulosic biomass into ethanol and hydrogen. Identification and characterization of protein complexes in C. thermocellum are important toward understanding its metabolism and physiology.

Results A two dimensional blue native/SDS-PAGE procedure was developed to separate membrane protein complexes of C. thermocellum. Proteins spots were identified by MALDI-TOF/TOF Mass spectrometry. 24 proteins were identified representing 13 distinct protein complexes, including several putative intact complexes. Interestingly, subunits of both the F1-F0-ATP synthase and the V1-V0-ATP synthase were detected in the membrane sample, indicating C. thermocellum may use alternative …

Staphylococcus Aureus And Escherichia Coli Have Disparate Dependences On Ksga For Growth And Ribosome Biogenesis, Heather Colleen O'Farrell, Jason P. Rife

Physiology and Biophysics Publications and Presentations

Background The KsgA methyltransferase has been conserved throughout evolution, methylating two adenosines in the small subunit rRNA in all three domains of life as well as in eukaryotic organelles that contain ribosomes. Understanding of KsgA’s important role in ribosome biogenesis has been recently expanded in Escherichia coli; these studies help explain why KsgA is so highly conserved and also suggest KsgA’s potential as an antimicrobial drug target.

Results We have analyzed KsgA’s contribution to ribosome biogenesis and cell growth in Staphylococcus aureus. We found that deletion of ksgA in S. aureus led to a cold-sensitive growth phenotype, although KsgA was …

The Interdomain Linker Of Aav-2 Rep68 Is An Integral Part Of Its Oligomerization Domain: Role Of A Conserved Sf3 Helicase Residue In Oligomerization, Francisco Zarate-Perez, Martino Bardelli, John W. Burgner Ii, Maria Villamil-Jarauta, Kanni Das, Demet Kekilli, Jorge Mansilla-Soto, R. Michael Linden, Carlos R. Escalante

Physiology and Biophysics Publications and Presentations

The four Rep proteins of adeno-associated virus (AAV) orchestrate all aspects of its viral life cycle, including transcription regulation, DNA replication, virus assembly, and site-specific integration of the viral genome into the human chromosome 19. All Rep proteins share a central SF3 superfamily helicase domain. In other SF3 members this domain is sufficient to induce oligomerization. However, the helicase domain in AAV Rep proteins (i.e. Rep40/Rep52) as shown by its monomeric characteristic, is not able to mediate stable oligomerization. This observation led us to hypothesize the existence of an as yet undefined structural determinant that regulates Rep oligomerization. In this …

Hyphenated Artists: A Body Of Potential, Laura Reeder

Journal of Social Theory in Art Education

The author of this article, an art teacher, arts education advocate, teaching artist, pre-service art teacher supervisor and instructor confronts “either/or” professional identities in arts education. Multi-faceted artist/scholar/educator/ learner/advocate/personas are “unfenced” in order to navigate spaces of artistic, educational, and cultural production without having to pause for identification at borders. In this form, pedagogies for inventive social change emerge. Dialogue among fields of artists and educators links either/or, artist/teacher qualities in holistic and interdisciplinary descriptions such as artist-teacher, teaching-artist, etc. The hyphenated association has become postmodern shorthand for inclusive “both/and” professional identities that in the 21st century may be limiting …

Ethnicity And Impressions Of Personality Using The Five-Factor Model: Stereotyping Or Cultural Sensitivity?, Andrea Kay Cooper, David Chin Evans

Ethnic Studies Review

The current research investigates whether communities use ethnicity as a cue when forming personality impressions of others. Past research has shown that dress, smiling, hairstyle, and even facial symmetry of targets produce systematic differences in personality impressions across the domains of the Five Factor model of personality. We investigated whether the stated or apparent ethnicity of groups and individuals also produce stereotypic impressions of personality. This study compared impressions across members and non-members of the target groups and examined "cue utility" i.e. whether impressions of the groups agreed with aggregated self-impressions by group members. In all, the results clearly suggest …

Opposing Roles Of The Μ-Opioid And Nociceptin/Orphanin Fq Receptors In Oligodendrocyte Development And Myelination, Allison Vestal-Laborde

Theses and Dissertations

While the classical function of myelin is to facilitate saltatory conduction, this membrane and the myelin-making oligodendrocytes (OLGs) are now recognized as regulators of plasticity and remodeling in the central nervous system (CNS). Thus, OLG maturation and myelination are highly vulnerable processes along CNS development. We previously showed that rat brain myelination is altered by perinatal exposure to buprenorphine, an opioid analogue in clinical trials for the treatment of pregnant opioid addicts. We now found that the in vivo effects on myelination could result from direct alteration in the balance between μ-opioid receptor (MOR) and nociceptin/orphanin FQ receptor (NOPR) activities …

Artemis And Metnase Mediated Processing Of 3΄-Blocked Dna Lesions: Role In Radio/Chemoresistance And Dna Repair, Susovan Mohapatra

Theses and Dissertations

DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the resolution of terminally blocked DNA DSBs is the biologically relevant function of Artemis, Artemis deficient fibroblasts were stably complemented with wild type or an endonuclease deficient D165N mutant Artemis. Physiological levels of wild type (WT) Artemis completely restored DSB repair proficiency and resistance to γ-radiation, bleomycin, and neocarzinostatin. Cells expressing the D165N mutants remained as chemo/radiosensitive and as repair deficient …

Biobehavioral Correlates In Fibromyalgia, Ann Trivigno Mcnallen

Theses and Dissertations

Introduction: Fibromyalgia (FMS) is a chronic pain syndrome characterized by non-restorative sleep, and fatigue. Over 75% of individuals with FMS complain of poor sleep quality and fatigue. These have been ranked by patients with FMS as having great impact on quality of life. A literature review suggested that poor sleep quality may be a predictor of increased stress and FMS symptom onset in those affected. However, no experimental studies have demonstrated a causal relationship between poor sleep and stress in people with FMS. Methods: Using a single stage cross-sectional design, the primary study aim was to compare 25 women with …

The Role Of Fyn And B-Cell Expressed Adam10 In Early B Cell Development, Germinal Center Formation And Terminal B Cell Differentiation, Natalia Chaimowitz

Theses and Dissertations

In these studies we sought to determine the role of Fyn kinase and ADAM10 in B cell biology. A disintegrin and metalloproteinase 10 (ADAM10) is a zinc dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. In particular, ADAM10 has been identified as a key regulator of lymphocyte development. Here we report that ADAM10 is dispensable for early B cell development within the bone marrow. However, deletion of ADAM10 from all peripheral B cells or in post-switch cells leads to severe …

The Role Of High Affinity Nicotinic Acetylcholine Receptors On Anxiety-Like Behavior: A Study In Female Mice, Jessicka Hall

Theses and Dissertations

Tobacco dependence is high in women who suffer from anxiety disorders yet little is known about the contributions of nicotinic acetylcholine receptors (nAChRs) on anxiety-like behavior. β2*nAChRs (*denotes assembly with other subunits) are the most abundantly expressed nAChRs in the brain yet little is known about the contributions of β2*nAChRs on anxiety-like behavior in female mice. In this study, antagonism and nicotine effects on anxiety-like behavior was investigated across the life span in 6, 12 and 24-month-old drug-naïve knockout (KO), heterozygous (HET) and a gain of function α6L9S mice and wild type (WT). HET mice showed increased sensitivity to di-hydrobeta-erythroidine …

Non-Canonical Roles For Stat1 And Stat2 In Mitochondrial Biogenesis And Fasting Homeostasis., Jennifer Sisler

Theses and Dissertations

The signal transducer and activator of transcription 1 (STAT1) and 2 (STAT2) are primarily activated by interferons and play a central role in orchestrating responses to a variety of pathogens by activating the transcription of nuclear encoded genes that mediate antiviral, antigrowth and immune surveillance responses. In addition to their nuclear effects, we report that STAT1 and STAT2 inhibit the expression of mitochondrial encoded mRNAs by activating type I interferons (IFNβ) under basal conditions. STAT1-/- livers also exhibit elevated levels of nuclear encoded components of the electron transport chain (ETC). Treatment of wild-type mice with IFNβ inhibits both mitochondrial and …