Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

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. Poland, 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 …

Pf19 Encodes The P60 Catalytic Subunit Of Katanin And Is Required For Assembly Of The Flagellar Central Apparatus In Chlamydomonas, Erin E. Dymek, Elizabeth F. Smith

Dartmouth Scholarship

For all eukaryotic cilia the basal bodies provide a template for the assembly of the doublet microtubules, and intraflagellar transport provides a mechanism for transport of axonemal components into the growing cilium. What is not known is how the central pair of microtubules is nucleated or how their associated polypeptides are assembled. Here we report that the Chlamydomonas pf19 mutation results in a single amino acid change within the p60 catalytic subunit of katanin, and that this mutation prevents microtubule severing activity. The pf19 mutant has paralyzed flagella that lack the central apparatus. Using a combination of mutant analysis, RNAi-mediated …

Dialogues, Dilemmas, And Disclosures: Genomic Research And Incidental Findings, Lynn W. Bush, Karen H. Rothenberg

Faculty Scholarship

No abstract provided.

Reducing False-Positive Prediction Of Minimotifs With A Genetic Interaction Filter, Jerlin Camilus Merlin, Sanguthevar Rajasekaran, Tian Mi, Martin Schiller

Life Sciences Faculty Research

Background

Minimotifs are short contiguous peptide sequences in proteins that have known functions. At its simplest level, the minimotif sequence is present in a source protein and has an activity relationship with a target, most of which are proteins. While many scientists routinely investigate new minimotif functions in proteins, the major web-based discovery tools have a high rate of false-positive prediction. Any new approach that reduces false-positives will be of great help to biologists.

Methods and Findings

We have built three filters that use genetic interactions to reduce false-positive minimotif predictions. The basic filter identifies those minimotifs where the source/target …

Occurrence Of Hormonal Residues In Feedlot Cattle Waste, Terry L. Mader, Leslie J. Johnson, Shannon L. Bartelt-Hunt, Daniel D. Snow, William Kranz, Charles Shapiro, Simon Van Donk, David P. Shelton, David Tarkalson, T. C. Zhang, Steve Ensley

Department of Animal Science: Faculty Publications

Two identically designed studies were conducted in separate years at the UNL Haskell Agricultural Laboratory using 192 crossbred heifers (96/study). Within a study heifers (initial weight = 386kg) were randomly assigned to 2 groups (3 42.4 m × 14.6 m pens/group/year): 1) treatment (TRT) animals were administered synthetic hormones via subcutaneous implants [d 1, 36 mg zearalonal; d 35, 140 mg trenbolone acetate (TBA) and 14 mg of 17β-estradiol benzoate (Revalor-H)] and fed Melengesterol Acetate (MGA), and 2) control (CON) animals with no synthetic hormone provided. Throughout each study, feedlot pen surface samples were obtained from 4 equally-sized zones (5 …

Proteins: Form And Function, Roy D. Sleator

Department of Biological Sciences Publications

An overwhelming array of structural variants has evolved from a comparatively small number of protein structural domains; which has in turn facilitated an expanse of functional derivatives. Herein, I review the primary mechanisms which have contributed to the vastness of our existing, and expanding, protein repertoires. Protein function prediction strategies, both sequence and structure based, are also discussed and their associated strengths and weaknesses assessed.

Use Of A Complete-Feed Diet (Ramp) To Rapidly Transition Cattle To A Finishing Diet, C. J. Schneider, Brandon L. Nuttelman, Dirk Burken, Terry J. Klopfenstein, Galen E. Erickson

Department of Animal Science: Faculty Publications

A study evaluated transitioning cattle from RAMP to a finishing diet with fewer intermediate step diets and days fed during transition. Yearling crossbred steers (n = 390; BW = 341 ± 14 kg) were blocked and stratified by BW, and assigned randomly within strata to 40 feedlot pens, with 9 or 10 steers per pen. Treatments were different grain adaptation programs (27 or 28 d) involving blends of RAMP and finishing diet. A control adaptation program involved decreasing RAMP and increasing a 62.5% corn finishing diet (62.5% high moisture corn (HMC), 25% sweet bran, 7.5% alfalfa hay (AH), and 5% …

Anaerobic Digestion Of Finishing Cattle Manure With And Without Distillers Grains In The Diet., Andrea K. Watson, Terry J. Klopfenstein, Galen E. Erickson, Samodha C. Fernando, Jana L. Harding, Adam L. Shreck

Department of Animal Science: Faculty Publications

Two treatments (cattle diet) were used in anaerobic digestion of finishing cattle manure. Diet 1 contained 82.5% dry rolled corn (DRC) (CONT) and diet 2 contained 40% wet distillers grains plus solubles (DM basis) replacing DRC (WDGS). Cattle were housed in stanchions for 3 d with complete manure collection in a cement pit. Manure (feces and urine) was sampled and analyzed for minerals, DM and OM. Manure collected was weighed into individual allotments based on DM and frozen. Continuously stirred anaerobic digesters (n = 7, 1 L capacity) were inoculated and maintained for 5 mo before the trial to ensure …

Use Of A Complete-Feed Diet (Ramp) In Grain Adaptation Programs Compared To Traditional Grain Adaptation Programs, C. J. Schneider, Brandon L. Nuttelman, Kelsey M. Rolfe Rolfe, William A. Griffin, Terry J. Klopfenstein, Galen E. Erickson

Department of Animal Science: Faculty Publications

A study evaluated using RAMP to adapt cattle to a high grain finishing diet. Yearling crossbred steers (n = 229; BW = 397 ± 28.4 kg) were consecutively weighed over 2 d, stratified by BW, and assigned randomly within strata to 18 feedlot pens, with 12 or 13 steers per pen. Treatments were imposed during grain adaptation (22 d) by decreasing RAMP (100 to 0%) and increasing finishing diet (0 to 100%). RAMP was fed either as a blend in a 1-diet system which was delivered twice daily (RAMP-1RS) or as 2 daily diets where RAMP was delivered in one …

Spatial Genetic Variation Among Spodoptera Frugiperda (Lepidoptera: Noctuidae) Sampled From The United States, Puerto Rico, Panama, And Argentina, Difabachew K. Belay, Pete L. Clark, Steven R. Skoda, David J. Isenhour, Jaime Molina-Ochoa, Claudia Gianni, John E. Foster

Department of Entomology: Faculty Publications

Spatial genetic variability of the fall armyworm, Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), was studied by collecting samples from 31 locations in the United States, Argentina, Panama, and Puerto Rico, and then using amplified fragment length polymorphism to detect genetic variation. Analysis of molecular variance showed significant genetic variation in fall armyworm among all (28%) sample locations and individuals within (71%) sample locations; genetic variation of fall armyworm was minimal between sample locations grouped into regions. The pairwise fixation index (F_ST) comparisons showed significant genetic differentiation (0.288) among the 31 locations. However, dendrograms of results from cluster …

Akirin Links Twist-Regulated Transcription With The Brahma Chromatin Remodeling Complex During Embryogenesis, Scott J. Nowak, Hitoshi Aihara, Katie Gonzalez, Yutaka Nibu, Mary K. Baylies

Faculty Articles

The activities of developmentally critical transcription factors are regulated via interactions with cofactors. Such interactions influence transcription factor activity either directly through protein–protein interactions or indirectly by altering the local chromatin environment. Using a yeast double-interaction screen, we identified a highly conserved nuclear protein, Akirin, as a novel cofactor of the key Drosophila melanogaster mesoderm and muscle transcription factor Twist. We find that Akirin interacts genetically and physically with Twist to facilitate expression of some, but not all, Twist-regulated genes during embryonic myogenesis. akirin mutant embryos have muscle defects consistent with altered regulation of a subset of Twistregulated genes. To …

Pseudoscorpion Mitochondria Show Rearranged Genes And Genome-Wide Reductions Of Rna Gene Sizes And Inferred Structures, Yet Typical Nucleotide Composition Bias, Sergey Ovchinnikov, Susan E. Masta

Biology Faculty Publications and Presentations

Pseudoscorpions are chelicerates and have historically been viewed as being most closely related to solifuges, harvestmen, and scorpions. No mitochondrial genomes of pseudoscorpions have been published, but the mitochondrial genomes of some lineages of Chelicerata possess unusual features, including short rRNA genes and tRNA genes that lack sequence to encode arms of the canonical cloverleaf-shaped tRNA. Additionally, some chelicerates possess an atypical guanine-thymine nucleotide bias on the major coding strand of their mitochondrial genomes.

We sequenced the mitochondrial genomes of two divergent taxa from the chelicerate order Pseudoscorpiones. We find that these genomes possess unusually short tRNA genes that do …

Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing The Myth That 20% Of The Human Genome Is Patented, Christopher M. Holman

IP Theory

No abstract provided.

Sparse Integrative Clustering Of Multiple Omics Data Sets, Ronglai Shen, Sijian Wang, Qianxing Mo

Memorial Sloan-Kettering Cancer Center, Dept. of Epidemiology & Biostatistics Working Paper Series

High resolution microarrays and second-generation sequencing platforms are powerful tools to investigate genome-wide alterations in DNA copy number, methylation, and gene expression associated with a disease. An integrated genomic profiling approach measuring multiple omics data types simultaneously in the same set of biological samples would render an integrated data resolution that would not be available with any single data type. In a previous publication (Shen et al., 2009), we proposed a latent variable regression with a lasso constraint (Tibshirani, 1996) for joint modeling of multiple omics data types to identify common latent variables that can be used to cluster patient …

Genes And Plays: Bringing Elsi Issues To Life, Karen H. Rothenberg, Lynn W. Bush

Faculty Scholarship

Ethical complexities surround the promise of genomic technology and the power of genetic information as they alter conceptions of identity and dynamics within personal and professional relationships. Creative approaches such as dramatic vignettes offer a unique analytical stage for imagining the bioethical past and future. Dramatic narratives can bring to life images of differing perspectives and values when experiencing innovations in medicine. Although the scientific landscape shifts, concerns expressed in theatre from 50 years ago parallel many contemporary ELSI (ethical, legal and social implications) issues, highlighting the ongoing struggle to appreciate the impact of emerging genetic technologies on relationships. To …

Cranial Variation And The Transition To Agriculture In Europe, Ron Pinhasi, Noreen Von Cramon-Taubadel

Human Biology Open Access Pre-Prints

Debates surrounding the nature of the Neolithic demographic transition in Europe have historically centred on two opposing models; a 'demic' diffusion model whereby incoming farmers from the Near East and Anatolia effectively replaced or completely assimilated indigenous Mesolithic foraging communities and an 'indigenist' model resting on the assumption that ideas relating to agriculture and animal domestication diffused from the Near East, but with little or no gene flow. The extreme versions of these dichotomous models have been heavily contested primarily on the basis of archaeological and modern genetic data. However, in recent years there has been a growing acceptance of …

The Y-Chromosome C3* Star-Cluster Attributed To Genghis Khan's Descendants Is Present At High Frequency In The Kerey Clan From Kazakhstan, Serikbai Abilev, Boris Malyarchuk, Miroslava Derenko, Marcin Wozniak, Tomasz Grzybowski, Ilya Zakharov

Human Biology Open Access Pre-Prints

In order to verify the possibility that the Y-chromosome C3* star-cluster attributed to Genghis Khan and his patrilineal descendants is relatively frequent in the Kereys, who are the dominant clan in Kazakhstan and in Central Asia as a whole, polymorphism of the Y-chromosome was studied in Kazakhs, represented mostly by members of the Kerey clan. The Kereys showed the highest frequency (76.5%) of individuals carrying the Y-chromosome variant known as C3* star-cluster ascribed to the descendants of Genghis Khan. C3* star-cluster haplotypes were found in two sub-clans, Abakh-Kereys and Ashmaily-Kereys, diverged about 20-22 generations ago according to the historical data. …

Pten Regulation Of Local And Long-Range Connections In Mouse Auditory Cortex, Qiaojie Xiong, Hysell V. Oviedo, Lloyd C. Trotman, Anthony M. Zador

Publications and Research

Autism spectrum disorders (ASDs) are highly heritable developmental disorders caused by a heterogeneous collection of genetic lesions. Here we use a mouse model to study the effect on cortical connectivity of disrupting the ASD candidate gene PTEN (phosphatase and tensin homolog deleted on chromosome 10). Through Cre-mediated recombination, we conditionally knocked out PTEN expression in a subset of auditory cortical neurons. Analysis of long-range connectivity using channelrhodopsin-2 revealed that the strength of synaptic inputs from both the contralateral auditory cortex and from the thalamus onto PTEN-cko neurons was enhanced compared with nearby neurons with normal PTEN expression. Laser-scanning photostimulation showed …

Structural Characterization Of Human Uch37, E. S. Burgie, C. Bingman, Ameet Soni, G. N. Phillips Jr.

Computer Science Faculty Works

Uch37 is a de-ubiquitylating enzyme that is functionally linked with the 26S proteasome via Rpn13, and is essential for metazoan development. Here, we report the X-ray crystal structure of full-length human Uch37 at 2.95 Å resolution. Uch37's catalytic domain is similar to those of all UCH enzymes characterized to date. The C-terminal extension is elongated, predominantly helical and contains coiled coil interactions. Additionally, we provide an initial characterization of Uch37's oligomeric state and identify a systematic error in previous analyses of Uch37 activity. Taken together, these data provide a strong foundation for further analysis of Uch37's several functions.

Probabilistic Ensembles For Improved Inference In Protein-Structure Determination, Ameet Soni, J. Shavlik

Computer Science Faculty Works

Protein X-ray crystallography — the most popular method for determining protein structures — remains a laborious process requiring a great deal of manual crystallographer effort to interpret low-quality protein images. Automating this process is critical in creating a high-throughput protein-structure determination pipeline. Previously, our group developed ACMI, a probabilistic framework for producing protein-structure models from electron-density maps produced via X-ray crystallography. ACMI uses a Markov Random Field to model the three-dimensional (3D) location of each non-hydrogen atom in a protein. Calculating the best structure in this model is intractable, so ACMI uses approximate inference methods to estimate the optimal structure. …

Vegfa Family Isoforms Regulate Spermatogonial Stem Cell Homeostasis In Vivo, Kyle C. Caires, Jeanene M. Clopton, Andrea S. Cupp, Derek J. Mclean

Department of Animal Science: Faculty Publications

The objective of the present study was to investigate vascular endothelial growth factor A (VEGFA) isoform regulation of cell fate decisions of spermatogonial stem cells (SSC) in vivo. The expression pattern and cell-specific distribution of VEGF isoforms, receptors, and coreceptors during testis development postnatal d 1–180 suggest a nonvascular function for VEGF regulation of early germ cell homeostasis. Populations of undifferentiated spermatogonia present shortly after birth were positive for VEGF receptor activation as demonstrated by immunohistochemical analysis. Thus, we hypothesized that proangiogenic isoforms of VEGF (VEGFA₁₆₄) stimulate SSC self-renewal, whereas antiangiogenic isoforms of VEGF (VEGFA₁₆₅b) …

Emerging Viruses In The Felidae: Shifting Paradigms, Stephen J. O'Brien, Jennifer L. Troyer, Meredith Brown, Warren E. Johnson, Agostinho Antunes, Melody E. Roelke, Jill Pecon-Slattery

Biology Faculty Articles

The domestic cat is afflicted with multiple viruses that serve as powerful models for human disease including cancers, SARS and HIV/AIDS. Cat viruses that cause these diseases have been studied for decades revealing detailed insight concerning transmission, virulence, origins and pathogenesis. Here we review recent genetic advances that have questioned traditional wisdom regarding the origins of virulent Feline infectious peritonitis (FIP) diseases, the pathogenic potential of Feline Immunodeficiency Virus (FIV) in wild non-domestic Felidae species, and the restriction of Feline Leukemia Virus (FeLV) mediated immune impairment to domestic cats rather than other Felidae species. The most recent interpretations indicate important …

Genome-Wide Analysis Of Syntenic Gene Deletion In The Grasses, James C. Schnable, Michael Freeling, Eric Lyons

Department of Agronomy and Horticulture: Faculty Publications

The grasses, Poaceae, are one of the largest and most successful angiosperm families. Like many radiations of flowering plants, the divergence of the major grass lineages was preceded by a whole-genome duplication (WGD), although these events are not rare for flowering plants. By combining identification of syntenic gene blocks with measures of gene pair divergence and different frequencies of ancient gene loss, we have separated the two subgenomes present in modern grasses. Reciprocal loss of duplicated genes or genomic regions has been hypothesized to reproductively isolate populations and, thus, speciation. However, in contrast to previous studies in yeast and teleost …

Heterogeneity In Mitochondrial Morphology And Membrane Potential Is Independent Of The Nuclear Division Cycle In Multinucleate Fungal Cells, John P. Gerstenberger, Patricia Occhipinti, Amy S. Gladfelter

Dartmouth Scholarship

In the multinucleate filamentous fungus Ashbya gossypii, nuclei divide asynchronously in a common cytoplasm. We hypothesize that the division cycle machinery has a limited zone of influence in the cytoplasm to promote nuclear autonomy. Mitochondria in cultured mammalian cells undergo cell cycle-specific changes in morphology and membrane potential and therefore can serve as a reporter of the cell cycle state of the cytoplasm. To evaluate if the cell cycle state of nuclei in A. gossypii can influ

Desert Hedgehog Is A Mammal-Specific Gene Expressed During Testicular And Ovarian Development In A Marsupial, William A. O'Hara

Master's Theses

Desert hedgehog (DHH) belongs to the hedgehog gene family that act as secreted intercellular signal transducers. DHH is an essential morphogen for normal testicular development and function in both mice and humans but is not present in the avian lineage. Like other hedgehog proteins, DHH signals through the patched (PTCH) receptors 1 and 2. Here we examine the expression and protein distribution of DHH, PTCH1 and PTCH2 in the developing testes of a marsupial mammal (the tammar wallaby) to determine whether DHH signalling is a conserved factor in gonadal development in all therian mammals.

Tumor Suppression By Cell Competition Through Regulation Of The Hippo Pathway, Chiao-Lin Chen, Molly C. Schroeder, Madhuri Kango-Singh, Chunyao Tao, Georg Halder

Biology Faculty Publications

Homeostatic mechanisms can eliminate abnormal cells to prevent diseases such as cancer. However, the underlying mechanisms of this surveillance are poorly understood. Here we investigated how clones of cells mutant for the neoplastic tumor suppressor gene scribble (scrib) are eliminated from Drosophila imaginal discs. When all cells in imaginal discs are mutant for scrib, they hyperactivate the Hippo pathway effector Yorkie (Yki), which drives growth of the discs into large neoplastic masses. Strikingly, when discs also contain normal cells, the scrib− cells do not overproliferate and eventually undergo apoptosis through JNK-dependent mechanisms. However, induction of apoptosis does …

Increased Variability Of Microbial Communities In Restored Salt Marshes Nearly 30 Years After Tidal Flow Restoration, Anne E. Bernhard, David Marshall, Lazaros Yiannos

Biology Faculty Publications

We analyzed microbial diversity and community composition from four salt marsh sites that were impounded for 40–50 years and subsequently restored and four unimpounded sites in southeastern Connecticut over one growing season. Community composition and diversity were assessed by terminal restriction fragment length polymorphism (TRFLP) and sequence analysis of 16S ribosomal RNA (rRNA) genes. Our results indicated diverse communities, with sequences representing 14 different bacterial divisions. Proteobacteria, Bacteroidetes, and Planctomycetes dominated clone libraries from both restored and unimpounded sites. Multivariate analysis of the TRFLP data suggest significant site, sample date, and restoration status effects, but the exact causes of these …

Parenting As Phenotype: A Behavioral Genetic Approach To Understanding Parenting, Shirley Mcguire, Nancy Segal, S. Hershberger

Psychology

This article discusses the behavioral genetic (BG) approach to parenting. Parenting is considered a phenotype that can be influenced by nature and nurture. Genetic contributions to parenting are conceptualized as evidence of genotype–environment correlation (rGE). Early BG studies focused on demonstrating that some parenting dimensions were heritable due to passive and evocative rGE processes. Current studies are investigating moderators and mediators of genetic and environmental contributions to parenting. The paper uses parent and child report data on parental warmth from the Twins, Adoptees, Peers, and Siblings study to illustrate the BG approach. Results show that heritability is …

Comparative Analysis Of Grapevine Whole-Genome Gene Predictions, Functional Annotation, Categorization And Integration Of The Predicted Gene Sequences, Jerome Grimplet, John Van Hemert, Pablo Carbonell-Bejerano, Jose Diaz-Riquelme, Julie Dickerson, Anne Fennell Dr, Mario Pezzotti, Jose M. Martinez-Zapater

Agronomy, Horticulture and Plant Science Faculty Publications

Background: The first draft assembly and gene prediction of the grapevine genome (8X base coverage) was made available to the scientific community in 2007, and functional annotation was developed on this gene prediction. Since then additional Sanger sequences were added to the 8X sequences pool and a new version of the genomic sequence with superior base coverage (12X) was produced.
Results: In order to more efficiently annotate the function of the genes predicted in the new assembly, it is important to build on as much of the previous work as possible, by transferring 8X annotation of the genome to the …