Genetics and Genomics Commons^™

Kaposi’S Sarcoma-Associated Herpesvirus Seropositivity Is Associated With Type 2 Diabetes Mellitus: A Case–Control Study In Xinjiang, China, Meng Cui, Qiwen Fang, Jun Zheng, Zhanjun Shu, Yin Chen, Yage Fan, Juan Zhao, Charles Wood, Tiejun Zhang, Yan Zeng

Nebraska Center for Virology: Faculty Publications

Objective: To assess the potential relationship between Kaposi’s sarcoma-associated herpesvirus (KSHV) infection and type 2 diabetes mellitus (DM-2) in Xinjiang, China.

Methods: A case–control study of consecutively included DM-2 patients and normal controls was conducted among the Uygur and Han populations in Xinjiang Uygur Autonomous Region, China. Blood samples were collected and KSHV seroprevalence, antibody titers, and viral load were investigated. Logistic regression analysis and multiple linear regression analysis were applied to explore determinants of the main outcome measures.

Results: A total of 324 patients with DM-2 and 376 normal controls were included. The seroprevalence of KSHV was 49.1% (95% …

Gene Gangs Of The Chloroviruses: Conserved Clusters Of Collinear Monocistronic Genes, Phillip Seitzer, Adrien Jeanniard, Fangrui Ma, James L. Van Etten, Marc T. Facciotti, David D. Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses (family Phycodnaviridae) are dsDNA viruses found throughout the world’s inland waters. The open reading frames in the genomes of 41 sequenced chloroviruses (330 + 40 kbp each) representing three virus types were analyzed for evidence of evolutionarily conserved local genomic “contexts”, the organization of biological information into units of a scale larger than a gene. Despite a general loss of synteny between virus types, we informatically detected a highly conserved genomic context defined by groups of three or more genes that we have termed “gene gangs”. Unlike previously described local genomic contexts, the definition of gene gangs requires only …

Susceptibility Genes To Plant Viruses, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Plant viruses use cellular factors and resources to replicate and move. Plants respond to viral infection by several mechanisms, including innate immunity, autophagy, and gene silencing, that viruses must evade or suppress. Thus, the establishment of infection is genetically determined by the availability of host factors necessary for virus replication and movement and by the balance between plant defense and viral suppression of defense responses. Host factors may have antiviral or proviral activities. Proviral factors condition susceptibility to viruses by participating in processes essential to the virus. Here, we review current advances in the identification and characterization of host factors …

Acute Exposure Of Primary Rat Soleus Muscle To Zilpaterol Hcl (Β2 Adrenergic Agonist), Tnfα, Or Il-6 In Culture Increases Glucose Oxidation Rates Independent Of The Impact On Insulin Signaling Or Glucose Uptake, Caitlin N. Cadaret, Kristin A. Beede, Hannah E. Riley, Dustin T. Yates

Department of Animal Science: Faculty Publications

Recent studies show that adrenergic agonists and inflammatory cytokines can stimulate skeletal muscle glucose uptake, but it is unclear if glucose oxidation is similarly increased. Thus, the objective of this study was to determine the effects of ractopamine HCl (β1 agonist), zilpaterol HCl (β2 agonist), TNFα, and IL-6 on glucose uptake and oxidation rates in unstimulated and insulin-stimulated soleus muscle strips from adult Sprague-Dawley rats. Effects on phosphorylation of Akt (phospho-Akt), p38 MAPK (phospho-p38), and p44/42 MAPK (phospho-p44/42) was also determined. Incubation with insulin increased (P < 0.05) glucose uptake by ~47%, glucose oxidation by ~32%, and phospho-Akt by ~238%. Insulin also increased (P < 0.05) phospho-p38, but only after 2 hours in incubation. Muscle incubated with β2 agonist alone exhibited ~20% less (P < 0.05) glucose uptake but ~32% greater (P < 0.05) glucose oxidation than unstimulated muscle. Moreover, co-incubation with insulin + β2 agonist increased (P < 0.05) glucose oxidation and phospho-Akt compared to insulin alone. Conversely, β1 agonist did not appear to affect basal or insulin-stimulated glucose metabolism, and neither β agonist affected phospho-p44/42. TNFα and IL-6 increased (P < 0.05) glucose oxidation by ~23% and ~33%, respectively, in the absence of insulin. This coincided with increased (P < 0.05) phospho-p38 and phospho-p44/42 but not phospho-Akt. Furthermore, co-incubation of muscle with insulin + either cytokine yielded glucose oxidation rates that were similar to insulin alone, despite lower (P < 0.05) phospho-Akt. Importantly, cytokine-mediated increases in glucose oxidation rates were not concomitant with greater glucose uptake. These results show that acute β2 adrenergic stimulation, but not β1 stimulation, directly increases fractional glucose oxidation in the absence of insulin and synergistically increases glucose oxidation when combined with insulin. The cytokines, TNFα and IL-6, likewise directly increased glucose oxidation in the absence of insulin, but were not additive in combination with insulin and in fact appeared to disrupt Akt-mediated insulin signaling. Rather, cytokines appear to be acting through MAPKs to elicit effects on glucose oxidation. Regardless, stimulation of glucose oxidation by these key stress factors did not rely upon greater glucose uptake, which may promote metabolic efficiency during acute stress by increasing fractional glucose oxidation without increasing total glucose consumption by muscle.

Genomic Investigation Of Beta Agonist Supplementation And Heat Stress In Livestock Species, Rachel Marie Kubik

College of Education and Human Sciences: Dissertations, Theses, and Student Research

β-adrenergic agonists (β-AA), commonly fed to cattle during the last 20-40 days of the finishing period, improve muscle growth by decreasing adipose deposition and increasing muscle accretion. In most cases, final live weights, hot carcass weight and average daily gain have all been shown to increase when β-AA are feed while fed intake, back fat, and marbling all decrease. Two β-AA, Ractopamine HCl (β1-AA) and Zilpaterol HCl (β2-AA) are currently approved for use in beef cattle in the United States. Converse to the beneficial effects of β-AA, heat stress in livestock decreases production efficiency and growth. There have also been …

The Effect Of Maoa And Stress Sensitivity On Crime And Delinquency: A Replication Study, Christa C. Christ, Joseph A. Schwartz, Scott F. Stoltenberg, Jonathan R. Brauer, Jukka Savolainen

Department of Psychology: Faculty Publications

Across several meta-analyses, MAOA-uVNTR genotype has been associated with an increased risk for antisocial behavior among males who experienced early life adversity. Subsequently, early life stress and genetic susceptibility may have long-term effects on stress sensitivity later in life. In support of this assumption, a recent study found evidence, in two independent samples, for a three-way interaction effect (cG × E × E) such that proximate stress was found to moderate the interactive effect of MAOA-uVNTR and distal stress on crime and delinquency among males. In light of recent developments in cG × E research, we attempted to …

Stability Of The Human Faecal Microbiome In A Cohort Of Adult Men, Raaj S. Mehta, David A. Drew, Jason Lloyd-Price, Ayshwarya Subramaian, Paul Lochhead, Amit D. Joshi, Kerry L. Ivey, Hamed Khalili, Gordon T. Brown, Casey Dulong, Mingyang Song, Long H. Nguyen, Himel Mallick, Eric B. Rimm, Jacques Izard, Curtis Huttenhower, Andrew T. Chan, Galeb S. Abu-Ali

Department of Food Science and Technology: Faculty Publications

Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples—one pair collected 24–72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such …

Recta: Regulon Identification Based On Comparative Genomics And Transcriptomics Analysis, Xin Chen, Anjun Ma, Adam Mcdermaid, Hanyuan Zhang, Chao Liu, Huansheng Cao, Qin Ma

School of Computing: Faculty Publications

Regulons, which serve as co-regulated gene groups contributing to the transcriptional regulation of microbial genomes, have the potential to aid in understanding of underlying regulatory mechanisms. In this study, we designed a novel computational pipeline, regulon identification based on comparative genomics and transcriptomics analysis (RECTA), for regulon prediction related to the gene regulatory network under certain conditions. To demonstrate the effectiveness of this tool, we implemented RECTA on Lactococcus lactis MG1363 data to elucidate acid-response regulons. A total of 51 regulons were identified, 14 of which have computational-verified significance. Among these 14 regulons, five of them were computationally predicted to …

Asas-Ssr Triennnial Reproduction Symposium: Looking Back And Moving Forward—How Reproductive Physiology Has Evolved: Fetal Origins Of Impaired Muscle Growth And Metabolic Dysfunction: Lessons From The Heat-Stressed Pregnant Ewe, Dustin T. Yates, Jessica Lynn Petersen, Ty B. Schmidt, Caitlin N. Cadaret, Taylor L. Barnes, Robert J. Posont, Kristin A. Beede

Department of Animal Science: Faculty Publications

Intrauterine growth restriction (IUGR) is the second leading cause of perinatal mortality and predisposes offspring to metabolic disorders at all stages of life. Muscle-centric fetal adaptations reduce growth and yield metabolic parsimony, beneficial for IUGR fetal survival but detrimental to metabolic health after birth. Epidemiological studies have reported that IUGRborn children experience greater prevalence of insulin resistance and obesity, which progresses to diabetes, hypertension, and other metabolic disorders in adulthood that reduce quality of life. Similar adaptive programming in livestock results in decreased birth weights, reduced and inefficient growth, decreased carcass merit, and substantially greater mortality rates prior to maturation. …

Changes In Myoblast Responsiveness To Tnfα And Il-6 Contribute To Decreased Skeletal Muscle Mass In Intrauterine Growth Restricted Fetal Sheep, Robert J. Posont, Kristin A. Beede, Sean W. Limesand, Dustin T. Yates

Department of Animal Science: Faculty Publications

Intrauterine growth restriction (IUGR) is a leading cause of perinatal morbidity and mortality (Alisi et al., 2011). Skeletal muscle growth is disproportionately reduced in IUGR fetuses and offspring (Padoan et al. 2004; Yates et al. 2014). These individuals present with reduced muscle mass and increased risk for metabolic disorders at all stages of life (Godfrey and Barker, 2000; Yates et al. 2016.). Muscle growth requires proliferation, differentiation, and fusion of myoblasts (muscle stem cells) to form muscle fibers early in gestation and to increase myonuclear content of existing fibers during late gestation and after birth (Yates et al., 2014). These …

Impaired Muscle Stem Cell Function In Cows With High Concentrations Of Androstenedione In Their Follicular Fluid, Taylor L. Barnes, Kiristen A. Beede, Elena M. Merrick, Caitlin N. Cadaret, Andrea S. Cupp, Dustin T. Yates

Department of Animal Science: Faculty Publications

It is unclear whether androstenedione (A4) increases muscle mass and strength similar to testosterone or whether it produces primarily catabolic effects on muscle-like estrogen (Rasmussen et al., 2000). Summers et al. (2014) observed two populations of cows that exhibit either high (>40 ng/mL; High A4) or low (<20 ng/mL; Low A4) concentrations of A4 within the fluid of the dominant follicle just prior to ovulation. High A4 cows had decreased reproductive rates and shorter times before falling out of the herd, but those that did produce calves weaned them ~10-kg heavier than their low A4 counterparts (Summers et al., 2014). It appears that the difference in weights is due to faster growing and more efficient skeletal muscle. High A4 cows share many characteristics with women suffering from polycystic ovary syndrome (PCOS), whose high levels of circulating androgens are associated with changes in body composition (Kirchengast and Huber, 2001).

Performance And Carcass Characteristics Of Steers Fed With Two Levels Of Metabolizable Energy Intake During Summer And Winter Season, R A. Arias, J P. Keim, M Gandarillas, A Velasquez, C Alvarado-Gilis, T L. Mader

Department of Animal Science: Faculty Publications

Climate change is producing an increase on extreme weather events around the world such as flooding, drought and extreme ambient temperatures impacting animal production and animal welfare. At present, there is a lack of studies addressing the effects of climatic conditions associated with energy intake in finishing cattle in South American feed yards. Therefore, two experiments were conducted to assess the effects of environmental variables and level of metabolizable energy intake above maintenance requirements (MEI) on performance and carcass quality of steers. In each experiment (winter and summer), steers were fed with 1.85 or 2.72 times of their requirements of …

Sustained Maternal Inflammation During The Early Third Trimester Yields Fetal Adaptations That Impair Subsequent Skeletal Muscle Growth And Glucose Metabolism In Sheep, Cailtin N. Cadaret, Elena M. Merrick, Taylor L. Barnes, Kristin A. Beede, Robert J. Posont, Jessica Lynn Petersen, Dustin T. Yates

Department of Animal Science: Faculty Publications

Intrauterine growth restriction (IUGR) is linked to metabolic dysfunction in offspring, but the mediating mechanisms are still under investigation (Barker et al., 1993). IUGR fetuses adapt to their poor intrauterine environment by repartitioning nutrients to organs critical for survival (i.e., brain, heart) at the expense of tissues such as muscle (Yates et al., 2012c). These developmental adaptations help the fetus to survive in utero but have lifelong consequences in offspring; persistent reduction of highly metabolic muscle mass is detrimental to glucose homeostasis (DeFronzo et al., 1981). Glucose metabolism is regulated primarily by insulin, and nutrient depravation is associated with impaired …

Breeding For Resistance In California Strawberry To Verticillium Dahliae, Zachary Christman

Department of Agronomy and Horticulture: Dissertations, Theses, and Student Research

This article focuses on breeding resistant strawberries to the fungus Verticillium dahliae, common name Verticillium wilt. This is a serious fungal disease that can result in a loss of 50% or more of a strawberry harvest when grown in infested soil. The main goal is to provide an example of how a cultivar can be made more resistant to a plant pathogen with the use of plant breeding methods.

Since 1930 the University of California, Davis, has been developing strawberry cultivars that are adapted to the agricultural industry and regional farms. Developing cultivars that require fewer inputs are of …

Copy Number Variation In The Porcine Genome Detected From Whole-Genome Sequence, Rebecca Anderson

Honors Program: Senior Projects (Public)

Copy number variations (CNVs) are large insertions, deletions, and duplications in the genome that vary between individuals in a species. These variations are known to impact a broad range of phenotypes from molecular-level traits to higher-order clinical phenotypes. CNVs have been linked to complex traits in humans such as autism, attention deficit hyperactivity disorder, nervous system disorders, and early-onset extreme obesity. In this study, whole-genome sequence was obtained from 72 founders of an intensely phenotyped experimental swine herd at the U.S. Meat Animal Research Center (USMARC) in Clay Center, Nebraska. This included 24 boars (12 Duroc and 12 Landrace) and …

Genetic Diversity And Distinctness Of Wild Nebraska Hops And Hop Cultivars (Humulus Lupulus L.), Megan Franklin

Honors Program: Senior Projects (Public)

Background Commercial hop (Humulus lupulus) cultivars that are being grown in the Midwest are not performing as successfully as when they are grown in the Pacific Northwest, the region to which they are adapted. To increase adaptation to the Midwest environment, one strategy is to draw from the genetic pool of wild native Midwest hops, which have developed genes that allow them to grow successfully in this environment. Wild hop plants that are genetically distinct from commercial cultivars are likely to have more adaptations, such as pest/disease resistance and drought tolerance, which can be bred into commercial lines. The …

Investigation Of Cry3bb1 Resistance And Intoxication In Western Corn Rootworm By Rna Sequencing, Leslie Catherine Rault, Blair D. Siegfried, Aaron J. Gassmann, Haichuan Wang, Gary J. Brewer, Nicholas J. Miller

Department of Entomology: Faculty Publications

The western corn rootworm (WCR) Diabrotica virgifera virgifera LeConte is a major pest of corn that has evolved resistance to transgenic maize that produces insecticidal Cry toxins. The specific mode of action of Cry3Bb1 and mechanism of resistance in WCR are unknown. This study compared gene expression between Cry3Bb1-susceptible and Cry3Bb1-resistant WCR neonates, in the presence and absence of Cry3Bb1. RNA-Seq data were analyzed to identify differentially expressed transcripts between strains of WCR, providing candidate transcripts for resistance to Cry3Bb1. Constitutive and Cry3Bb1-induced differences between strains caused the differential expression of 608 transcripts after 8 hr. Differentially expressed transcripts between …

Eight-Legged Encounters—Arachnids, Volunteers, And Art Help To Bridge The Gap Between Informal And Formal Science Learning, Eileen Hebets, Melissa Welch-Lazoritz, Pawl Tisdale, Patricia Wonch Hill

Eileen Hebets Publications

Increased integration and synergy between formal and informal learning environments is proposed to provide multiple benefits to science learners. In an effort to better bridge these two learning contexts, we developed an educational model that employs the charismatic nature of arachnids to engage the public of all ages in science learning; learning that aligns with the Next Generation Science Standards (NGSS Disciplinary Core Ideas associated with Biodiversity and Evolution). We created, implemented, and evaluated a family-focused, interactive science event—Eight-Legged Encounters (ELE)—which encompasses more than twenty modular activities. Volunteers facilitated participant involvement at each activity station and original …

Biophysical Approaches To Solve The Structures Of The Complex Glycan Shield Of Chloroviruses, Cristina De Castro, Garry Duncan, Domenico Garozzo, Antonio Molinaro, Luisa Sturiale, Michela Tonetti, James L. Van Etten

James Van Etten Publications

The capsid of Paramecium bursaria chlorella virus (PBCV-1) contains a heavily glycosylated major capsid protein, Vp54. The capsid protein contains four glycans, each N-linked to Asn. The glycan structures are unusual in many aspects: (1) they are attached by a β-glucose linkage, which is rare in nature; (2) they are highly branched and consist of 8–10 neutral monosaccharides; (3) all four glycoforms contain a dimethylated rhamnose as the capping residue of the main chain, a hyper-branched fucose residue and two rhamnose residues ''with opposite absolute configurations; (4) the four glycoforms differ by the nonstoichiometric presence of two monosaccharides, l-arabinose and …

Comparing Snp Panels And Statistical Methods For Estimating Genomic Breed Composition Of Individual Animals In Ten Cattle Breeds, Jun He, Yage Guo, Jiaqi Xu, Hao Li, Anna Fuller, Richard G. Tait Jr., Xiao-Lin Wu, Stewart Bauck

Department of Child, Youth, and Family Studies: Faculty Publications

Background: SNPs are informative to estimate genomic breed composition (GBC) of individual animals, but selected SNPs for this purpose were not made available in the commercial bovine SNP chips prior to the present study. The primary objective of the present study was to select five common SNP panels for estimating GBC of individual animals initially involving 10 cattle breeds (two dairy breeds and eight beef breeds). The performance of the five common SNP panels was evaluated based on admixture model and linear regression model, respectively. Finally, the downstream implication of GBC on genomic prediction accuracies was investigated and discussed in …

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T_FH) cells, and T follicular regulatory (T_FR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T_FH/T_FR cells in the GC contributes to the …

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4⁺ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4⁺ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …

Methylation-Based Enrichment Facilitates Low-Cost, Noninvasive Genomic Scale Sequencing Of Populations From Feces, Kenneth L. Chiou, Christina M. Bergey

United States Public Health Resources

Obtaining high-quality samples from wild animals is a major obstacle for genomic studies of many taxa, particularly at the population level, as collection methods for such samples are typically invasive. DNA from feces is easy to obtain noninvasively, but is dominated by bacterial and other non-host DNA. The high proportion of non-host DNA drastically reduces the efficiency of high-throughput sequencing for host animal genomics. To address this issue, we developed an inexpensive capture method for enriching host DNA from noninvasive fecal samples. Our method exploits natural differences in CpG-methylation density between vertebrate and bacterial genomes to preferentially bind and isolate …

Triennial Reproduction Symposium: Looking Back And Moving Forward—How Reproductive Physiology Has Evolved, Deb L. Hamernik, Andrea S. Cupp, John S. Davis

Department of Animal Science: Faculty Publications

In honor of the 50th anniversary of the Society for the Study of Reproduction (SSR), a Triennial Reproduction Symposium was cosponsored by SSR and the American Society of Animal Science (ASAS). The Society for the Study of Reproduction was formed in 1967 when a group of reproductive biologists that were members of ASAS met with physician scientists and decided to organize a new scientific society. The goal of SSR was to promote the study of reproduction by fostering interdisciplinary communication among scientists, holding conferences, and publishing meritorious studies. Today after its 50th anniversary, the mission for SSR is to harness …

National Beef Quality Audit–2016: Assessment Of Cattle Hide Characteristics, Offal Condemnations, And Carcass Traits To Determine The Quality Status Of The Market Cow And Bull Beef Industry, Mckensie K. Harris, L. Clay Eastwood, Courtney A. Boykin, Ashley N. Arnold, Kerri B. Gehring, Daniel S. Hale, Christopher R. Kerth, Davey B. Griffin, J.W. Savell, Keith E. Belk, Dale R. Woerner, Josh D. Hasty, Jennifer N. Martin, Ty E. Lawrence, Trenton J. Mcevers, Deborah L. Vanoverbeke, Gretchen G. Mafi, Morgan M. Pfeiffer, Ty B. Schmidt, Robert J. Maddock, D. Dwain Johnson, Chad C. Carr, Jason M. Scheffler, T. Dean Pringle, Alexander M. Stelzleni, Robert J. Delmore Jr.

Department of Animal Science: Faculty Publications

To continue the series that began in 1994, the National Beef Quality Audit (NBQA) – 2016 was conducted to quantify the quality status of the market cow and bull beef sector, as well as determine improvements made in the beef and dairy industry since 2007. The NBQA-2016 was conducted from March through December of 2016, and assessed hide-on carcasses (n = 5,278), chilled carcasses (n = 4,285), heads (n = 5,720), and offal items (n = 4,800) in 18 commercial processing facilities throughout the United States. Beef cattle were predominantly black-hided; 68.0% of beef cows and 67.2% of beef bulls …

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 10⁴ TCID₅₀) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …

Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …

Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …

Including Phenotypic Causal Networks In Genome-Wide Association Studies Using Mixed Effects Structural Equation Models, Mehdi Momen, Ahmad Ayatollahi Mehrgardi, Mahmoud Amiri Roudbar, Andreas Kranis, Renan Mercuri Pinto, Bruno D. Valente, Gota Morota, Guilherme J.M. Rosa, Daniel Gianola

Department of Animal Science: Faculty Publications

Background: Phenotypic networks describing putative causal relationship among multiple phenotypes can be used to infer single-nucleotide polymorphism (SNP) effects in genome-wide association studies (GWAS). In GWAS with multiple phenotypes, reconstructing underlying causal structures among traits and SNPs using a single statistical framework is essential for understanding the entirety of genotype-phenotype maps. A structural equation model (SEM) can be used for such purpose.

Methods: We applied SEM to GWAS (SEM-GWAS) in chickens, taking into account putative causal relationships among body weight (BW), breast meat (BW), hen-house production (HHP), and SNPs. We assessed the performance of SEM-GWAS by comparing the model results …