Genetics and Genomics Commons^™

The N-Glycan Structures Of The Antigenic Variants Of Chlorovirus Pbcv-1 Major Capsid Protein Help To Identify The Virus-Encoded Glycosyltransferases, Immacolata Speciale, Garry A. Duncan, Luca Unione, Irina Agarkova, Domenico Garozzo, Jesus Jimenez-Barbero, Sicheng Lin, Todd L. Lowary, Antonio Molinaro, Eric Noel, Maria Elena Laugieri, Michela Tonetti, James L. Van Etten, Cristina De Castro

James Van Etten Publications

The chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) is a large dsDNA virus that infects the microalga Chlorella variabilis NC64A. Unlike most other viruses, PBCV-1 encodes most, if not all, of the machinery required to glycosylate its major capsid protein (MCP). The structures of the four N-linked glycans from the PBCV-1 MCP consist of nonasaccharides, and similar glycans are not found elsewhere in the three domains of life. Here, we identified the roles of three virus-encoded glycosyltransferases (GTs) that have four distinct GT activities in glycan synthesis. Two of the three GTs were previously annotated as GTs but the third …

Design And Characterization Of A Consensus Hemagglutinin Vaccine Immunogen Against H3 Influenza A Viruses Of Swine, Haiyan Sun, Jung-Hyang Sur, Sarah Vitosh-Sillman, David J. Steffen, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The substantial genetic diversity exhibited by influenza A viruses of swine (IAV-S) represents the main challenge for the development of a broadly protective vaccine against this important pathogen. The consensus vaccine immunogen has proven an effective vaccinology approach to overcome the extraordinary genetic diversity of RNA viruses. In this project, we sought to determine if a consensus IAV-S hemagglutinin (HA) immunogen would elicit broadly protective immunity in pigs. To address this question, a consensus HA gene (designated H3-CON.1) was generated from a set of 1,112 H3 sequences of IAV-S recorded in GenBank from 2011 to 2015. The consensus HA gene …

Reverse Genetics Systems As Tools To Overcome The Genetic Diversity Of Lassa Virus, Brett Beitzel, Christine E. Hulseberg, Gustavo Palacios

United States Army: Publications

Lassa virus is endemic in a large area of sub-Saharan Africa, and exhibits a large amount of genetic diversity. Of the four currently recognized lineages, lineages I–III circulate in Nigeria, and lineage IV circulates in Sierra Leone, Guinea, and Liberia. However, several newly detected lineages have been proposed. LASV genetic diversity may result in differences in pathogenicity or response to medical countermeasures, necessitating the testing of multiple lineages during the development of countermeasures and diagnostics. Logistical and biosafety concerns can make it difficult to obtain representative collections of divergent LASV clades for comparison studies. For example, lack of a cold …

Overview Of Direct Thrombin Inhibitors For Use In Staphylococcus Aereus Infections, Joseph C. Risler

Honors Undergraduate Theses

The pathogenicity and intractable nature of the microorganism Staphylococcus aureus (SA) has been long documented and highlighted by many health care agencies, with emphasis on its ability to exploit the human coagulation system to deadly effect. Two drugs from a class of inhibitors known as Direct Thrombin Inhibitors (DTI) have been shown to have a substantial effect on the enzyme secreted by SA known as Staphylocoagulase (SC), but up until now the application of this potential treatment has been limited. This paper strives to supply an overview of these clinical studies and propose a novel protocol for testing DTI's on …

Single-Cell Glia And Neuron Gene Expression In The Central Amygdala In Opioid Withdrawal Suggests Inflammation With Correlated Gut Dysbiosis., Sean J O'Sullivan, Evangelia Malahias, James Park, Ankita Srivastava, Beverly A S Reyes, Jon Gorky, Rajanikanth Vadigepalli, Elisabeth J Van Bockstaele, James S Schwaber

Articles, Abstracts, and Reports

Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably

Vitamin D Receptor Gene Polymorphisms Knowledge And Breast Cancer In Texas, Ejike Roland Egwuekwe

Walden Dissertations and Doctoral Studies

Breast cancer is a world health problem and is a leading cause of cancer-related death among women in the United States. However, breast cancer risks were reported to be reduced through exposure to Vitamin D through its Receptors identified as the p53 target gene. The purpose of this study was to assess the associations between VDR gene polymorphisms knowledge/awareness and decisions to reduce breast cancer risks and likelihood of mammogram screening among women in Texas. Data from survey were used. Roy adaptation model was the theoretical framework that guided this quasi- experimental, quantitative research. The dependent variables were decisions to …

An Inflammatory Landscape For Preoperative Neurologic Deficits In Glioblastoma., Amal Katrib, Hyun-Hwan Jeong, Nina L Fransen, Kristin S Henzel, Jeremy A Miller

Articles, Abstracts, and Reports

No abstract provided.

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

Chloroviruses Lure Hosts Through Long-Distance Chemical Signaling, David Dunigan, Maitham Ahmed Al-Sammak, Zeina Al-Ameeli, Irina Agarkova, John Delong, James L. Van Etten

James Van Etten Publications

Chloroviruses exist in aquatic systems around the planet where they infect certain eukaryotic green algae that are mutualistic endosymbionts in a variety of protists and metazoans. Natural chlorovirus populations are seasonally dynamic but the precise temporal changes in these populations and the mechanisms that underlie them have, heretofore, been unclear. We recently reported the novel concept that predator/prey-mediated virus activation regulates chlorovirus population dynamics, and in the current manuscript demonstrate virus packaged chemotactic modulation of prey behavior.

Viruses have not previously been reported to act as chemotactic/chemo-attractive agents. Rather, viruses as extracellular entities are generally viewed as non-metabolically active spore-like …

Conformational Flexibility In The Enterovirus Rna Replication Platform, Meghan S. Warden, Kai Cai, Gabriel Cornilescu, Jordan E. Burke, Komala Ponniah, Samuel E. Butcher, Steven M. Pascal

Chemistry & Biochemistry Faculty Publications

A presumed RNA cloverleaf (5′CL), located at the 5′-most end of the noncoding region of the enterovirus genome, is the primary established site for initiation of genomic replication. Stem–loop B (SLB) and stem–loop D (SLD), the two largest stem–loops within the 5′CL, serve as recognition sites for protein interactions that are essential for replication. Here we present the solution structure of rhinovirus serotype 14 5′CL using a combination of nuclear magnetic resonance spectroscopy and small-angle X-ray scattering. In the absence of magnesium, the structure adopts an open, somewhat extended conformation. In the presence of magnesium, the structure compacts, bringing SLB …

The Effect Of Maternal Dietary Habits During Pregnancy On Neonate Leptin Methylation Patterns And Gestational Age, Sean Fitzpatrick

Legacy Theses & Dissertations (2009 - 2024)

The health of a newborn baby is inextricably linked to the health status of its mother and in turn the mother’s diet during pregnancy. Leptin (LEP) is an adipokine hormone involved in metabolism regulation and has been linked fetal development through the hypothalamic-pituitary-adrenal axis (HPA). Prior work suggests that gestational epigenetic alterations the LEP gene may be sensitive to adverse exposures during pregnancy, which in turn could explain variation in neonate outcomes. However, no prior work has examined this possibility explicitly. The objective of this study was to investigate the association between dietary patterns of mothers during pregnancy and their …

Mechanisms Of Trinucleotide Repeat Instability During Dna Synthesis, Kara Y. Chan

Theses and Dissertations--Toxicology and Cancer Biology

Genomic instability, in the form of gene mutations, insertions/deletions, and gene amplifications, is one of the hallmarks in many types of cancers and other inheritable genetic disorders. Trinucleotide repeat (TNR) disorders, such as Huntington’s disease (HD) and Myotonic dystrophy (DM) can be inherited and repeats may be extended through subsequent generations. However, it is not clear how the CAG repeats expand through generations in HD. Two possible repeat expansion mechanisms include: 1) polymerase mediated repeat extension; 2) persistent TNR hairpin structure formation persisting in the genome resulting in expansion after subsequent cell division. Recent in vitro studies suggested that a …

The Effect Of Bovine Galectin-1, A Conceptus Secretory Protein, On The Endometrial Transcriptome, Lindsay Faye Grose

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early embryonic loss in cattle is detrimental to reproduction thus, the profitability of both the beef and dairy industries. Therefore, an important aspect of study is to find techniques that beef or dairy producers could use to decrease early embryonic loss Galectin-1, the protein that was investigated in this research is important in modulating the maternal immune system in rodent and human early pregnancies by promoting fetomaternal immune tolerance. The role of galectin-1 within the reproductive tissues has not been thoroughly investigated in cattle. Galectin-1 is located in the caruncular and intercaruncular regions of the bovine endometrium, specifically the maternal …

Investigating Neurogenesis As A Veritable Epigenetic Endophenotype For Alzheimer's Disease, Layne Wells

Scripps Senior Theses

Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by progressive amyloid plaque aggregation, neurofibrillary tangles, and cortical tissue death. As the prevalence of AD is projected to climb in coming years, there is a vested interest in identifying endophenotypes by which to improve diagnostics and direct clinical interventions. The risk for complex disorders, such as AD, is influenced by multiple genetic, environmental, and lifestyle factors. Significant strides have been made in identifying genetic variants linked to AD through the genome-wide association study (GWAS). It has been estimated in more recent years, however, that GWAS-identified variants account for limited …

Mutations Of Fus Cause Aggregation Of Rna Binding Proteins, Disruptions In Protein Synthesis, And Dysregulation Of Nonsense Mediated Decay, Marisa Elizabeth Kamelgarn

Theses and Dissertations--Toxicology and Cancer Biology

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the …

Multigenerational Genomic And Epigenetic Effects Of Manufactured Silver Nanomaterials In Caenorhabditis Elegans, Anye Wamucho

Theses and Dissertations--Toxicology and Cancer Biology

There has been an increase in the incorporation of silver nanomaterials into consumer products due to their antimicrobial properties. Therefore there is potential for silver nanoparticles (Ag-NPs) to leach out into the environment during different life-cycle stages of these nanomaterial-containing products. Concern about the toxicity of Ag-NPs has led to investigations into their toxic effects on a variety of organisms mainly using acute and sub-chronic, single-generation exposures. The focus of this project was to understand the effects of long-term continuous multigenerational exposure to AgNO₃ and Ag-NPs in both pristine and environmentally transformed forms, on the model organism, Caenorhabditis elegans …

A Poxvirus Pseudokinase Represses Viral Dna Replication Via A Pathway Antagonized By Its Paralog Kinase, Annabel T. Olson, Zhigang Wang, Amber B. Rico, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Poxviruses employ sophisticated, but incompletely understood, signaling pathways that engage cellular defense mechanisms and simultaneously ensure viral factors are modulated properly. For example, the vaccinia B1 protein kinase plays a vital role in inactivating the cellular antiviral factor BAF, and likely orchestrates other pathways as well. In this study, we utilized experimental evolution of a B1 deletion virus to perform an unbiased search for suppressor mutations and identify novel pathways involving B1. After several passages of the ΔB1 virus we observed a robust increase in viral titer of the adapted virus. Interestingly, our characterization of the adapted viruses reveals that …

Persistent Viral Reservoirs In Lymphoid Tissues In Siv-Infected Rhesus Macaques Of Chinese-Origin On Suppressive Antiretroviral Therapy, Summer Siddiqui, Stefanie Perez, Yong Gao, Lara Doyle-Meyers, Brian T. Foley, Qingsheng Li, Binhua Ling

Nebraska Center for Virology: Faculty Publications

Understanding HIV latent reservoirs in tissues is essential for the development of new strategies targeting these sites for eradication. Here, we assessed the size of latent reservoirs and the source of residual viruses in multiple lymphoid tissues of SIV-infected and fully suppressed rhesus macaques of Chinese-origin (cRMs). Eight cRMs were infected with SIVmac251 and treated with tenofovir and emtricitabine daily for 24 weeks initiated 4 weeks post-infection. Four of the eight animals reached sustained full viral suppression with undetectable viremia. The levels of cell-associated SIV DNA varied in peripheral blood mononuclear cells (PBMCs) and multiple lymphoid tissues, but with higher …

Relationship Between The Cervical Microbiome, Hiv Status, And Precancerous Lesions, Cameron Klein, Daniela Gonzalez, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Nirosh Aluthge, Samodha Fernando, John T. West, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Nearly all cervical cancers are causally associated with human papillomavirus (HPV). The burden of HPV-associated dysplasias in sub-Saharan Africa is influenced by HIV. To investigate the role of the bacterial microbiome in cervical dysplasia, cytobrush samples were collected directly from cervical lesions of 144 Tanzanian women. The V4 hypervariable region of the 16S rRNA gene was amplified and deep sequenced. Alpha diversity metrics (Chao1, PD whole tree, and operational taxonomic unit [OTU] estimates) displayed significantly higher bacterial richness in HIV-positive patients (P = 0.01) than in HIV-negative patients. In HIV-positive patients, there was higher bacterial richness in patients with …

Near-Atomic Structure Of A Giant Virus, Qianglin Fang, Dongjie Zhu, Irina Agarkova, Jagat Adhikari, Thomas Klose, Yue Liu, Zhenguo Chen, Yingyuan Sun, Michael L. Gross, James L. Van Etten, Xinzheng Zhang, Michael G. Rossmann

Nebraska Center for Virology: Faculty Publications

Although the nucleocytoplasmic large DNA viruses (NCLDVs) are one of the largest group of viruses that infect many eukaryotic hosts, the near-atomic resolution structures of these viruses have remained unknown. Here we describe a 3.5 Å resolution icosahedrally averaged capsid structure of Paramecium bursaria chlorella virus 1 (PBCV-1). This structure consists of 5040 copies of the major capsid protein, 60 copies of the penton protein and 1800 minor capsid proteins of which there are 13 different types. The minor capsid proteins form a hexagonal network below the outer capsid shell, stabilizing the capsid by binding neighboring capsomers together. The size …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

A Double Humanized Blt-Mice Model Featuring A Stable Human-Like Gut Microbiome And Human Immune System, Lance Daharsh, Jianshui Zhang, Amanda E. Ramer-Tait, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Humanized mice (hu-mice) that feature a functional human immune system have fundamentally changed the study of human pathogens and disease. They can be used to model diseases that are otherwise difficult or impossible to study in humans or other animal models. The gut microbiome can have a profound impact on human health and disease. However, the murine gut microbiome is very different than the one found in humans. There is a need for improved pre-clinical hu-mice models that have an engrafted human gut microbiome. Therefore, we created double hu-mice that feature both a human immune system and stable human-like gut …

The Vaccinia Virus (Vacv) B1 And Cellular Vrk2 Kinases Promote Vacv Replication Factory Formation Through Phosphorylation-Dependent Inhibition Of Vacv B12, Annabel T. Olson, Zhigang Wang, Annabel Olson, Alexandria C. Linville, Brianna L. Bullard, Eric A. Weaver, Clinton Jones, Matthew S. Wiebe

Nebraska Center for Virology: Faculty Publications

Comparative examination of viral and host protein homologs reveals novel mechanisms governing downstream signaling effectors of both cellular and vi- ral origin. The vaccinia virus B1 protein kinase is involved in promoting multiple facets of the virus life cycle and is a homolog of three conserved cellular enzymes called vaccinia virus-related kinases (VRKs). Recent evidence indicates that B1 and VRK2 mediate a com- mon pathway that is largely uncharacterized but appears independent of previous VRK substrates. Interestingly, separate studies described a novel role for B1 in inhibiting vac- cinia virus protein B12, which otherwise impedes an early event in the …

Harnessing Population Genetics For Pest Management: Theory And Application For Urban Rats, Matthew Combs, Kaylee Byers, Chelsea Himsworth, Jason Munshi-South

Human–Wildlife Interactions

Effective management of rodent pests requires an ecological understanding of how they move through their environment and how those movements influence the invasion, persistence, or reinvasion of problematic colonies. Traditional methodologies used to describe rodent movement patterns, such as mark-recapture, are hindered by their time-consuming nature and limited geographic scope. As such, our understanding of how rodents interact with urban environments remains limited. Population genetic principles and tools have the capacity to greatly increase our understanding of rodent population dynamics, ecological relationships, and movements across space, but this field is often unapproachable to non-scientist pest management professionals (PMPs). In this …

Evidence-Based Practice Self-Study Education Program For Staff Nurses On Genomics, Nancy L. Norman-Marzella

Walden Dissertations and Doctoral Studies

Nurses routinely obtain genomic data when collecting family health histories. However, they report low confidence in their knowledge and understanding of genomics and the genetically engineered medications prescribed for their patients. The purpose of this project was the development and implementation of an evidence-based online education program about genetics and genomics to increase the nurses' understanding and ability to provide competent care for their patients receiving treatments based on the science of genomics. Knowles's principles of adult learning theory guided the development and delivery of the online education project to 12 medical-surgical registered nurses employed in a hospital in the …

Clonally Expanded Alpha-Chain T-Cell Receptor (Tcr) Transcripts Are Present In Aneurysmal Lesions Of Patients With Abdominal Aortic Aneurysm (Aaa), Song Lu, John V. White, Raquel I. Judy, Lisa L. Merritt, Wan Lu Lin, Xiaoying Zhang, Charalambos Solomides, Ifeyinwa Nwaneshiudu, John Gaughan, Dimitri S. Monos, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts. The amplified transcripts were cloned and sequenced. Substantial proportions …

Translational Insights Into The Genetic Etiology Of Mental Health Disorders: Examining Risk Factor Models, Neuroimaging, And Current Dissemination Practices, Jessica L. Bourdon

Theses and Dissertations

Psychiatric genetics is a basic science field that has potential for practical application and effective translation. To date, translational frameworks utilized by this field have been linear (e.g., sequential) in nature, focusing on molecular genetic information. It is proposed that non-linear (e.g., socio-ecological) frameworks are a better way to immediately translate non-molecular genetic information. This dissertation explored the translation of psychiatric genetic information in two ways. First, a survey was sent to academic stakeholders to assess the state of the science regarding the translation of genetic information to the clinical care of mental health disorders. Findings from this indicate a …

Genome-Wide Systems Genetics Of Alcohol Consumption And Dependence, Kristin Mignogna

Theses and Dissertations

Widely effective treatment for alcohol use disorder is not yet available, because the exact biological mechanisms that underlie this disorder are not completely understood. One way to gain a better understanding of these mechanisms is to examine the genetic frameworks that contribute to the risk for developing this disorder. This dissertation examines genetic association data in combination with gene expression networks in the brain to identify functional groups of genes associated with alcohol consumption and dependence.

The first study took advantage of the behavioral complexity of human samples, and experimental capabilities provided by mouse models, by co-analyzing gene expression networks …

Efficient Region-Based Test Strategy Uncovers Genetic Risk Factors For Functional Outcome In Bipolar Disorder, Monika Budde, Stefanie Friedrichs, Ney Alliey-Rodriguez, Seth Ament, Judith A. Badner

School of Medicine Publications

Genome-wide association studies of case-control status have advanced the understanding of the genetic basis of psychiatric disorders. Further progress may be gained by increasing sample size but also by new analysis strategies that advance the exploitation of existing data, especially for clinically important quantitative phenotypes. The functionally-informed efficient region-based test strategy (FIERS) introduced herein uses prior knowledge on biological function and dependence of genotypes within a powerful statistical framework with improved sensitivity and specificity for detecting consistent genetic effects across studies. As proof of concept, FIERS was used for the first genome-wide single nucleotide polymorphism (SNP)-based investigation on bipolar disorder …

Efficacy Of A T Cell-Biased Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, Matthew J. Gorman, Michael S. Diamond, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) is a major public health concern due to the risk of congenital Zika syndrome in developing fetuses and Guillain-Barre syndrome in adults. Currently, there are no approved vaccines available to protect against infection. Adenoviruses are safe and highly immunogenic vaccine vectors capable of inducing lasting humoral and cellular immune responses. Here, we developed two Adenovirus (Ad) vectored Zika virus vaccines by inserting a ZIKV prM-E gene expression cassette into human Ad types 4 (Ad4-prM-E) and 5 (Ad5-prM-E). Immune correlates indicate that Ad5-prM-E vaccination induces both an anti-ZIKV antibody and T-cell responses whereas Ad4-prM-E vaccination only induces a …