Medicine and Health Sciences Commons^™

Targeting The Endocannabinoid System To Reduce Inflammatory Pain, Sudeshna Ghosh

Theses and Dissertations

The endogenous cannabinoids (endocannabinoids) anandamide (AEA) and 2-arachidonylglycerol (2-AG) exert their effects predominantly through cannabinoid CB1 and CB2 receptors, but these actions are short-lived because of rapid hydrolysis by fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), respectively. Selective inhibition of either enzyme elevates CNS levels of the appropriate endocannabinoid and produces analgesic effects with fewer psychomimetic side effects than Δ9-tetrahydrocannabinol (THC), the primary active constituent of marijuana. While cannabinoid receptor agonists and FAAH inhibitors reliably produce anti-inflammatory and anti-hyperalgesic effects in the carrageenan test and other inflammatory pain models, much less is known about the consequences of inhibiting …

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 …

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 …

Profiling Plasma Peptides For The Identification Of Potential Ageing Biomarkers In Chinese Han Adults, Jiapeng Lu, Yuqing Huang, Youxin Wang, Yan Li, Youjun Zhang, Jingjing Wu, Feifei Zhao, Shijiao Meng, Xinwei Yu, Qingwei Ma, Manshu Song, Naibai Chang, Alan H. Bittles, Wei Wang

Research outputs 2012

Advancing age is associated with cardiovascular disease, diabetes mellitus and cancer, and shows significant inter-individual variability. To identify ageing-related biomarkers we performed a proteomic analysis on 1890 Chinese Han individuals, 1136 males and 754 females, aged 18 to 82 years, using weak cation exchange magnetic bead based MALDI-TOF-MS analysis. The study identified 44 peptides which varied in concentration in different age groups. In particular, apolipoprotein A-I (ApoA1) concentration gradually increased between 18 to 50 years of age, the levels of fibrinogen alpha (FGA) decreased over the same age span, while albumin (ALB) was significantly degraded in middle-aged individuals. In addition, …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

Overt Cleft Palate Phenotype And Tbx1 Genotype Correlations In Velo-Cardio-Facial/Digeorge/22q11.2 Deletion Syndrome Patients, Sean Herman, Tingwei Guo, Donna M. Mcdonald Mcginn, Anna Blonska, Alan L. Shanske, Anne S. Bassett, Eva Chow, Mark Bowser, Molly Sheridan, Frits Beemer, Koen Devriendt, Ann Swillen, Jeroen Breckpot, Maria Christina Digilio, Bruno Marino, Bruno Dallapiccola, Courtney Carpenter, Xin Zheng, Jacob Johnson, Jonathan Chung, Anne Marie Higgins, Nicole Philip, Tony J. Simon, Karlene Coleman, Damian Heine Suñer, Jordi Rosell, Wendy R. Kates, Marcella Devoto, Elaine Zackai, Tao Wang, Robert J. Shprintzen, Beverly Emanuel, Bernice Morrow, International Chromosome 22q11.2 Consortium

Communication Disorders Faculty Publications

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000 – 1/4,000 live births. Approximately 9–11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown. The TBX1 gene, a member of the T-box transcription factor gene family, lies within the 22q11.2 region that is hemizygous in patients with 22q11DS. Inactivation of one allele of Tbx1 in the mouse does not result in CP, but inactivation of both alleles does. Based on these data, …

Msh2 Acts In Medium-Spiny Striatal Neurons As An Enhancer Of Cag Instability And Mutant Huntingtin Phenotypes In Huntington's Disease Knock-In Mice., Marina Kovalenko, Ella Dragileva, Jason St Claire, Tammy Gillis, Jolene R Guide, Jaclyn New, Hualing Dong, Raju Kucherlapati, Melanie H Kucherlapati, Michelle E Ehrlich, Jong-Min Lee, Vanessa C Wheeler

Farber Institute for Neuroscience Faculty Papers

The CAG trinucleotide repeat mutation in the Huntington's disease gene (HTT) exhibits age-dependent tissue-specific expansion that correlates with disease onset in patients, implicating somatic expansion as a disease modifier and potential therapeutic target. Somatic HTT CAG expansion is critically dependent on proteins in the mismatch repair (MMR) pathway. To gain further insight into mechanisms of somatic expansion and the relationship of somatic expansion to the disease process in selectively vulnerable MSNs we have crossed HTT CAG knock-in mice (HdhQ111) with mice carrying a conditional (floxed) Msh2 allele and D9-Cre transgenic mice, in which Cre recombinase is expressed specifically in MSNs …

A Novel Survival-Based Tissue Microarray Of Pancreatic Cancer Validates Muc1 And Mesothelin As Biomarkers., Jordan M Winter, Laura H Tang, David S Klimstra, Murray F Brennan, Jonathan R Brody, Flavio G Rocha, Xiaoyu Jia, Li-Xuan Qin, Michael I D'Angelica, Ronald P Dematteo, Yuman Fong, William R Jarnagin, Eileen M O'Reilly, Peter J Allen

Department of Surgery Faculty Papers

BACKGROUND: One-fifth of patients with seemingly 'curable' pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed 'unresectable' by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046).

METHODS AND FINDINGS: Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term …

Stroke Rehabilitation, Length-Of-Stay, And Re-Admission Rates: A Literature Review, Morgen Hagedorn

All Graduate Theses, Dissertations, and Other Capstone Projects

Stroke is shown to be a significant U.S. health problem with a profound impact on the nation’s rising healthcare costs (Hall, Levant, & DeFrances, 2012). Longer patient length-of-stay [LOS] and higher re-admission rates have brought consequences to healthcare systems as institutional budgets are unable to reconcile the additional services and the influx of healthcare demands. Through a comprehensive literature review, the author illustrates the general knowledge available on the stroke experience, on stroke care and rehabilitation, and on patient LOS and re-admission rates. The literature review is based on general medical research with a focus on the stroke population. The …

Insight Into Animal Cloning And The Food Chain: A Qualitative Examination Of Key Opinion Leaders And A Cross Section Of The Irish Public., Cathal Murphy

Masters

The ability to clone elite breeding animals, aimed at addressing the needs of modern food production, had been earmarked as a possibility for the agricultural sector since the birth of Dolly the sheep in 1996. A ruling by the Food and Drug Administration in the United States in 2008 that permits under-license, the commercial cloning of agricultural animals has seen this possibility realised. No such ruling exists here in Europe, but the FDA policy not to label cloned-derived products, and a history of wariness to food biotechnology in Europe may expedite this debate. With the plethora of issues that cloning …

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

Microrna-145 Protects Cardiomyocytes Against Hydrogen Peroxide (H₂O₂)-Induced Apoptosis Through Targeting The Mitochondria Apoptotic Pathway., Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu

Center for Translational Medicine Faculty Papers

MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-145 in either ischemia/reperfused mice myocardial tissues or H₂O₂-treated neonatal rat ventricle myocytes (NRVMs) was markedly down-regulated. Over-expression of miR-145 significantly inhibited the H₂O₂-induced cellular apoptosis, ROS production, mitochondrial structure disruption as well as the …

Is Etanercept A Safe And Effective Treatment For Ankylosing Spondylitis?, Robyn M. Albert

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not etanercept is a safe and effective treatment for ankylosing spondylitis (AS).

Study Design: Review of three English language randomized control trials published in 2007, 2008, and 2010.

Data Sources: Two double-blind placebo-controlled randomized controlled trials and one placebo-controlled randomized control trial comparing etanercept to placebo were found using PubMed.

Outcomes Measured: Work instability was measured through the Ankylosing Spondylitis Work Instability Scale (AS-WIS) based on scores of 1-20. Quality of life was measured through the EuroQOL-5D (EQ-5D), which assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. …

Is Dabigatran Non-Inferior To Warfarin For The Prevention Of Stroke In Those With Atrial Fibrillation?, Brittany Burlakoff

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not dabigatran 150 mg twice daily is non-inferior to warfarin for the prevention of stroke in those with atrial fibrillation with similar rates of bleeding events.

STUDY DESIGN: Review of 3 English language primary studies. All three trials were randomized controlled trials which were blinded for those receiving dabigatran and un-blinded for those receiving warfarin.

DATA SOURCES: Articles were found using PUBMED and COCHRANE databases.

OUTCOME MEASURED: The primary outcomes of these studies were either incidence of stroke or systemic embolism and/or major bleeding events.

RESULTS:The RE-LY …

Is 1.25 Mg Oral Fingolimod Effective In Reducing Relapses In Adults With Relapsing Multiple Sclerosis?, Caitlin M. Cook

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not is 1.25 mg oral fingolimod effective in reducing relapses in adults with relapsing multiple sclerosis.

STUDY DESIGN: Review of three English language primary studies published between 2006 and 2010.

DATA SOURCES: Randomized, double-blind, controlled clinical trials comparing daily 1.25 mg oral fingolimod to either identical placebo capsules or weekly intramuscular interferon beta-1a therapy were found using Pubmed and Cochrane Databases.

OUTCOMES MEASURED: Annualized relapse rate was assessed in all studies. Relapses were confirmed by neurologists and assessed using the Expanded Disability Status Scale (EDSS) to evaluate worsening …

Is Methylphenidate Transdermal System (Daytrana®) Safe And Effective For Managing Attention Deficit Hyperactivity Disorder Symptoms In Children?, Pamela Cassidy

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not methylphenidate transdermal system (Daytrana®) is safe and effective for managing attention deficit hyperactivity disorder symptoms in children.

STUDY DESIGN: A review of three English language studies published from 2006-2010. Includes two randomized, double-blind, controlled trials and one randomized, controlled crossover study.

DATA SOURCES: Randomized, placebo-controlled studies evaluating the effectiveness and safety of methylphenidate transdermal system (MTS) for managing attention deficit hyperactivity disorder (ADHD) symptoms in children were located using the PubMed, CINAHL, and Cochrane Library databases.

OUTCOMES MEASURED: The primary measures of effectiveness used were the …

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

Predicting Vision Loss In Healthy Aging With Manganese-Enhanced Mri Of The Rat Eye, David Bissig

Wayne State University Dissertations

In healthy aging, visual function declines throughout adulthood. Age-related changes in neuronal ion homeostasis -- specifically, increased Ca2+ influx through L-type voltage gated calcium channels (L-VGCCs) -- are believed to contribute to certain functional declines, but this possibility has not yet been tested in the neural retina. In young, mid- and old adult Long-Evans rats, we compared visual function (optokinetic tracking), as well as retinal physiology and eye morphology (Mn2+-enhanced MRI (MEMRI), which uses neuronal Mn2+ uptake as a marker of Ca2+ influx). We documented significant age-related decreases in visual performance and increases in retinal ion influx. We confirmed that …

Proteasome Regulation Of Caspase-8: Significance In Cancer, Michael Vincent Fiandalo

Theses and Dissertations--Molecular and Cellular Biochemistry

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin …

Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important …

Evidence That The Density Of Self Peptide-Mhc Ligands Regulates T-Cell Receptor Signaling., Nadia Anikeeva, Dimitry Gakamsky, Jørgen Schøller, Yuri Sykulev

Department of Microbiology and Immunology Faculty Papers

Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into oligomers that mimic pMHC clustering and examined how multivalency and density of the pMHCs in model clusters influences the binding to live CD8 T cells and the kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I proteins promotes their interaction with CD8 co-receptor, which plays a critical role …

Cns Neural/Glial Progenitors As Targets Of Hiv-1 And Opiates: Effects On Proliferation And Population Dynamics May Alter Behavior Outcomes., Yun Kyung Hahn

Theses and Dissertations

Human immunodeficiency virus (HIV) infected patients with a history of injection opiate abuse have higher incidences of acquired immunodeficiency syndrome (AIDS) and neurological dysfunction. The use of combined anti-retroviral therapy has significantly reduced the prevalence of mortality and progression to AIDS. Due to extended life expectancy, these patients are still at a great risk for HIV-associated neurological disorders and impairment in their later life. Neural progenitor cells (NPCs) play critical roles in brain growth and repair after injury and insult. Pediatric HIV patients whose glial populations are still developing are especially at risk for central nervous system (CNS) damage. Our …

Efficient And Robust Rna-Seq Process For Cultured Bacteria And Complex Community Transcriptomes, Georgia Giannoukos, Dawn M. Ciulla, Katherine Huang, Brian J. Haas, Jacques Izard, Joshua Z. Levin, Jonathan Livny, Ashlee M. Earl, Dirk Gevers, Doyle V. Ward, Chad Nusbaum, Bruce W. Birren, Andreas Gnirke

Department of Food Science and Technology: Faculty Publications

We have developed a process for transcriptome analysis of bacterial communities that accommodates both intact and fragmented starting RNA and combines efficient rRNA removal with strand-specific RNA-seq. We applied this approach to an RNA mixture derived from three diverse cultured bacterial species and to RNA isolated from clinical stool samples. The resulting expression profiles were highly reproducible, enriched up to 40-fold for non-rRNA transcripts, and correlated well with profiles representing undepleted total RNA.

Chloroviruses: Not Your Everyday Plant Virus, James L. Van Etten, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Viruses infecting higher plants are among the smallest viruses known and typically have four to ten protein-encoding genes. By contrast, many viruses that infect algae (classified in the virus family Phycodnaviridae) are among the largest viruses found to date and have up to 600 protein- encoding genes. This brief review focuses on one group of plaque-forming phycodnaviruses that infect unicellular chlorella-like green algae. The prototype chlorovirus PBCV-1 has more than 400 protein-encoding genes and 11 tRNA genes. About 40% of the PBCV-1 encoded proteins resemble proteins of known function including many that are completely unexpected for a virus. In many …

Molecular Genetic And Biochemical Characterization Of The Vaccinia Virus I3 Protein, The Replicative Single-Stranded Dna Binding Protein, Matthew D. Greseth, Kathleen A. Boyle, Matthew S. Bluma, Bethany Unger, Matthew S. Wiebe, Jamaria A. Soares-Martins, Nadi T. Wickramasekera, James Wahlberg, Paula Traktman

Nebraska Center for Virology: Faculty Publications

Vaccinia virus, the prototypic poxvirus, efficiently and faithfully replicates its approximately 200-kb DNA genome within the cytoplasm of infected cells. This intracellular localization dictates that vaccinia virus encodes most, if not all, of its own DNA replication machinery. Included in the repertoire of viral replication proteins is the I3 protein, which binds to single-stranded DNA (ssDNA) with great specificity and stability and has been presumed to be the replicative ssDNA binding protein (SSB). We substantiate here that I3 colocalizes with bromodeoxyuridine (BrdU)-labeled nascent viral genomes and that these genomes accumulate in cytoplasmic factories that are delimited by membranes derived from …

Lineage-Specific Differences Between Human And Simian Immunodeficiency Virus Regulation Of Gp120 Trimer Association And Cd4 Binding, Andrés Finzi, Beatriz Pacheco, Shi-Hua Xiang, Marie Pancera, Alon Herschhorn, Liping Wang, Xing Zeng, Anik Desormeaux, Peter D. Kwong, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both …

Subunit Organization Of The Membrane-Bound Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Liping Wang, Christopher Gu, Alon Herschhorn, Shi-Hua Xiang, Hillel Haim, Xinzhen Yang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The trimeric human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) spike is a molecular machine that mediates virus entry into host cells and is the sole target for virus-neutralizing antibodies. The mature Env spike results from cleavage of a trimeric gp160 precursor into three gp120 and three gp41 subunits. Here we describe an ~11-Å cryo-EM structure of the trimeric HIV-1 Env precursor in its unliganded state. The three gp120 and three gp41 subunits form a cage-like structure with an interior void surrounding the trimer axis. Interprotomer contacts are limited to the gp41 transmembrane region, the torus-like gp41 ectodomain, and …

Comparative Analysis Of The Fusion Efficiency Elicited By The Envelope Glycoprotein V1–V5 Regions Derived From Human Immunodeficiency Virus Type 1 Transmitted Perinatally, Hongyan Guo, Levon Abrahamyan, Chang Liu, Mackenzie Waltke, Yunqi Geng, Qimin Chen, Charles Wood, Xiaohong Kong

Nebraska Center for Virology: Faculty Publications

Understanding the properties of viruses preferentially establishing infection during perinatal transmission of human immunodeficiency virus type 1 (HIV-1) is critical for the development of effective measures to prevent transmission. A previous study demonstrated that the newly transmitted viruses (in infants) of chronically infected mother–infant pairs (MIPs) were fitter in terms of growth, which was imparted by their envelope (Env) glycoprotein V1–V5 regions, than those in the corresponding chronically infected mothers. In order to investigate whether the higher fitness of transmitted viruses was conferred by their higher entry efficiency directed by the V1–V5 regions during perinatal transmission, the fusogenicity of Env …

Antibody Responses To Lytic And Latent Human Herpesvirus 8 Antigens Among Hiv-Infected Patients In Central China, Tiejun Zhang, Na He, Yingying Ding, Qingwu Jiang, Charles Wood

Nebraska Center for Virology: Faculty Publications

Human herpesvirus 8 (HHV8) is an important opportunistic infection of HIV/AIDS. However, very little is known about antibody seropositivities to HHV8 lytic and latent antigens among HIVinfected patients in China. Therefore, a cross-sectional study was conducted to explore HHV8 serostatus among 316 HIV-infected patients in a rural area of central China. The antibody seropositivity to HHV8 ORF65 (lytic) and LANA (latent) antigens was 12.7% and 10.4%, respectively. Patients who were naïve to antiretroviral therapy (ART) were more likely to be seropositive for antibodies to ORF65 (OR: 3.79; 95% CI: 1.71–8.42) and LANA (OR: 3.77; 95% CI: 1.55–9.14) than patients receiving …

Heme Oxygenase-1 Regulates The Immune Response To Influenza Virus Infection And Vaccination In Aged Mice, Nathan W. Cummins, Eric A. Weaver, Shannon M. May, Anthony J. Croatt, Oded Foreman, Richard B. Kennedy, Gregory A. Polan, Michael A. Barry, Karl A. Nath, Andrew D. Badley

Nebraska Center for Virology: Faculty Publications

Underlying mechanisms of individual variation in severity of influenza infection and response to vaccination are poorly understood. We investigated the effect of reduced heme oxygenase-1 (HO-1) expression on vaccine response and outcome of influenza infection. HO-1-deficient and wild-type (WT) mice (kingdom, Animalia; phylum, Chordata; genus/species, Mus musculus) were infected with influenza virus A/PR/8/34 with or without prior vaccination with an adenoviral-based influenza vaccine. A genome-wide association study evaluated the expression of single-nucleotide polymorphisms (SNPs) in the HO-1 gene and the response to influenza vaccination in healthy humans. HO-1-deficient mice had decreased survival after influenza infection compared to WT mice (median …