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Positive Selection Shaped The Convergent Evolution Of Independently Expanded Kallikrein Subfamilies Expressed In Mouse And Rat Saliva Proteomes, Robert C. Karn, Christina M. Laukaitis 2011 Butler University

Positive Selection Shaped The Convergent Evolution Of Independently Expanded Kallikrein Subfamilies Expressed In Mouse And Rat Saliva Proteomes, Robert C. Karn, Christina M. Laukaitis

Scholarship and Professional Work - LAS

We performed proteomics studies of salivas from the genome mouse (C57BL/6 strain) and the genome rat (BN/SsNHsd/Mcwi strain). Our goal was to identify salivary proteins with one or more of three characteristics that may indicate that they have been involved in adaptation: 1) rapid expansion of their gene families; 2) footprints of positive selection; and/or 3) sex-limited expression. The results of our proteomics studies allow direct comparison of the proteins expressed and their levels between the sexes of the two rodent species. Twelve members of the Mus musculus species-specific kallikrein subfamily Klk1b showed sex-limited expression in the mouse saliva proteomes. …


Inflated Type I Error Rates When Using Aggregation Methods To Analyze Rare Variants In The 1000 Genomes Project Exon Sequencing Data In Unrelated Individuals: Summary Results From Group 7 At Genetic Analysis Workshop 17, Nathan L. Tintle, Hugues Aschard, Inchi Hu, Nora Nock, Haitian Wang, Elizabeth Pugh 2011 Dordt College

Inflated Type I Error Rates When Using Aggregation Methods To Analyze Rare Variants In The 1000 Genomes Project Exon Sequencing Data In Unrelated Individuals: Summary Results From Group 7 At Genetic Analysis Workshop 17, Nathan L. Tintle, Hugues Aschard, Inchi Hu, Nora Nock, Haitian Wang, Elizabeth Pugh

Faculty Work Comprehensive List

As part of Genetic Analysis Workshop 17 (GAW17), our group considered the application of novel and standard approaches to the analysis of genotype-phenotype association in next-generation sequencing data. Our group identified a major issue in the analysis of the GAW17 next-generation sequencing data: type I error and false-positive report probability rates higher than those expected based on empirical type I error levels (as high as 90%). Two main causes emerged: population stratification and long-range correlation (gametic phase disequilibrium) between rare variants. Population stratification was expected because of the diverse sample. Correlation between rare variants was attributable to both random causes …


Identification Of Genetic Association Of Multiple Rare Variants Using Collapsing Methods, Yan V. Sun, Yun Ju Sung, Nathan L. Tintle, Andreas Ziegler 2011 Emory University

Identification Of Genetic Association Of Multiple Rare Variants Using Collapsing Methods, Yan V. Sun, Yun Ju Sung, Nathan L. Tintle, Andreas Ziegler

Faculty Work Comprehensive List

Next-generation sequencing technology allows investigation of both common and rare variants in humans. Exomes are sequenced on the population level or in families to further study the genetics of human diseases. Genetic Analysis Workshop 17 (GAW17) provided exomic data from the 1000 Genomes Project and simulated phenotypes. These data enabled evaluations of existing and newly developed statistical methods for rare variant sequence analysis for which standard statistical methods fail because of the rareness of the alleles. Various alternative approaches have been proposed that overcome the rareness problem by combining multiple rare variants within a gene. These approaches are termed collapsing …


The Arabidopsis Trithorax-Like Factor Atx1 Functions In Dehydration Stress Responses Via Aba-Dependent And Aba-Independent Pathways, Yong Ding, Zoya Avramova, Michael Fromm 2011 University of Nebraska Center for Biotechnology and Center for Plant Science Innovation and School of Biological Sciences

The Arabidopsis Trithorax-Like Factor Atx1 Functions In Dehydration Stress Responses Via Aba-Dependent And Aba-Independent Pathways, Yong Ding, Zoya Avramova, Michael Fromm

School of Biological Sciences: Faculty Publications

Emerging evidence suggests that the molecular mechanisms driving the responses of plants to environmental stresses are associated with specific chromatin modifications. Here, we demonstrate that the Arabidopsis trithorax-like factor ATX1, which trimethylates histone H3 at lysine 4 (H3K4me3), is involved in dehydration stress signaling in both abscisic acid (ABA)-dependent and ABA-independent pathways. The loss of function of ATX1 results in decreased germination rates, larger stomatal apertures, more rapid transpiration and decreased tolerance to dehydration stress in atx1 plants. This deficiency is caused in part by reduced ABA biosynthesis in atx1 plants resulting from decreased transcript levels from NCED3, which …


Copper Tolerance Of Saccharomyces Cerevisiae Nonsense-Mediated Mrna Decay Mutants, Rafael Deliz-Aguirre, Audrey L. Atkin, Bessie W. Kebaara 2011 Baylor University

Copper Tolerance Of Saccharomyces Cerevisiae Nonsense-Mediated Mrna Decay Mutants, Rafael Deliz-Aguirre, Audrey L. Atkin, Bessie W. Kebaara

School of Biological Sciences: Faculty Publications

The eukaryotic nonsense-mediated mRNA (NMD) is a specialized pathway that leads to the recognition and rapid degradation of mRNAs with premature termination codons, and importantly some natural mRNAs as well. Natural mRNAs with atypically long 3′-untranslated regions (UTRs) are degraded by NMD in Saccharomyces cerevisiae. A number of S. cerevisiae mRNAs undergo alternative 3′-end processing producing mRNA isoforms that differ in their 3′-UTR lengths. Some of these alternatively 3′-end processed mRNA isoforms have atypically long 3′-UTRs and would be likely targets for NMD-mediated degradation. Here, we investigated the role NMD plays in the regulation of expression of CTR2, …


Developmental Regulation Of Hemoglobin Synthesis In The Green Anole Lizard Anolis Carolinensis, Jay F. Storz, Federico G. Hoffmann, Juan C. Opazo, Thomas J. Sanger, Hideaki Moriyama 2011 University of Nebraska - Lincoln

Developmental Regulation Of Hemoglobin Synthesis In The Green Anole Lizard Anolis Carolinensis, Jay F. Storz, Federico G. Hoffmann, Juan C. Opazo, Thomas J. Sanger, Hideaki Moriyama

Jay F. Storz Publications

Tetrapod vertebrates possess multiple alpha- and beta-like globin genes that are ontogenetically regulated, such that functionally distinct hemoglobin (Hb) isoforms are synthesized during different stages of development. The alpha- and beta-like globin genes of amphibians, birds and mammals are differentially expressed during embryonic development and postnatal life, but little is known about the developmental regulation of globin gene expression in non-avian reptiles. Here we report an investigation into the developmental regulation of Hb synthesis in the green anole lizard Anolis carolinensis. We tested two hypotheses derived from comparative genomic studies of the globin gene clusters in tetrapod vertebrates. First, …


Evolutionary Origins Of Oxygen Sensing In Animals, Kalle T. Rytkönen, Jay F. Storz 2011 University of Turku, Finland

Evolutionary Origins Of Oxygen Sensing In Animals, Kalle T. Rytkönen, Jay F. Storz

Jay F. Storz Publications

All animal life requires molecular oxygen as the terminal electron acceptor in aerobic energy production. A lack of oxygen can reduce the rate of energy production, whereas an excess of oxygen leads to the accumulation of toxic reactive oxygen species. Hence, animals have evolved sophisticated mechanisms with which to monitor and respond to fluctuations in oxygen availability, in order to maintain cellular homeostasis. In all animal taxa examined so far, the maintenance of physiological oxygen homeostasis is mediated by the oxygen-dependent post-translational hydroxylation of a heterodimeric transcription factor, termed hypoxia-inducible factor (HIF; Kaelin & Ratcliffe, 2008). The hydroxylation reaction is …


Differential Loss And Retention Of Cytoglobin, Myoglobin, And Globin-E During The Radiation Of Vertebrates, Federico G. Hoffmann, Juan C. Opazo, Jay F. Storz 2011 University of Nebraska-Lincoln

Differential Loss And Retention Of Cytoglobin, Myoglobin, And Globin-E During The Radiation Of Vertebrates, Federico G. Hoffmann, Juan C. Opazo, Jay F. Storz

Jay F. Storz Publications

If rates of postduplication gene retention are positively correlated with levels of functional constraint, then gene duplicates that have been retained in a restricted number of taxonomic lineages would be expected to exhibit relatively low levels of sequence conservation. Paradoxical patterns are presented by gene duplicates that have been retained in a small number of taxa but which are nonetheless subject to strong purifying selection relative to paralogous members of the same multigene family. This pattern suggests that such genes may have been co-opted for novel, lineage-specific functions. One possible example involves the enigmatic globin-E gene (GbE), which …


Experimental Approaches To Evaluate The Contributions Of Candidate Protein-Coding Mutations To Phenotypic Evolution, Jay F. Storz, Anthony J. Zera 2011 University of Nebraska - Lincoln

Experimental Approaches To Evaluate The Contributions Of Candidate Protein-Coding Mutations To Phenotypic Evolution, Jay F. Storz, Anthony J. Zera

Jay F. Storz Publications

Identifying mechanisms of molecular adaptation can provide important insights into the process of phenotypic evolution, but it can be exceedingly difficult to quantify the phenotypic effects of specific mutational changes. To verify the adaptive significance of genetically based changes in protein function, it is necessary to document functional differences between the products of derived and wild-type alleles and to demonstrate that such differences impinge on higher-level physiological processes (and ultimately, fitness). In the case of metabolic enzymes, this requires documenting in vivo differences in reaction rate that give rise to differences in flux through the pathway in which the enzymes …


Analysis Of Biological Features Associated With Meiotic Recombination Hot And Cold Spots In Saccharomyces Cerevisiae, Loren Hansen, Nak-Kyeong Kim, Leonardo Mariño-Ramírez, David Landsman 2011 Old Dominion University

Analysis Of Biological Features Associated With Meiotic Recombination Hot And Cold Spots In Saccharomyces Cerevisiae, Loren Hansen, Nak-Kyeong Kim, Leonardo Mariño-Ramírez, David Landsman

Mathematics & Statistics Faculty Publications

Meiotic recombination is not distributed uniformly throughout the genome. There are regions of high and low recombination rates called hot and cold spots, respectively. The recombination rate parallels the frequency of DNA double-strand breaks (DSBs) that initiate meiotic recombination. The aim is to identify biological features associated with DSB frequency. We constructed vectors representing various chromatin and sequence-based features for 1179 DSB hot spots and 1028 DSB cold spots. Using a feature selection approach, we have identified five features that distinguish hot from cold spots in Saccharomyces cerevisiae with high accuracy, namely the histone marks H3K4me3, H3K14ac, H3K36me3, and H3K79me3; …


Critical Role Of Leucine-Valine Change In Distinct Low Ph Requirements For Membrane Fusion Between Two Related Retrovirus Envelopes, Marceline Côté, Yi-Min Zheng, Kun Li, Shi-Hua Xiang, Lorraine M. Albritton, Shan-Lu Liu 2011 Department of Microbiology and Immunology, McGill University

Critical Role Of Leucine-Valine Change In Distinct Low Ph Requirements For Membrane Fusion Between Two Related Retrovirus Envelopes, Marceline Côté, Yi-Min Zheng, Kun Li, Shi-Hua Xiang, Lorraine M. Albritton, Shan-Lu Liu

Nebraska Center for Virology: Faculty Publications

Many viruses use a pH-dependent pathway for fusion with host cell membrane, the mechanism of which is still poorly understood. Here we report that a subtle leucine (Leu)-valine (Val) change at position 501 in the envelope glycoproteins (Envs) of two related retroviruses, jaagsiekte sheep retro-virus (JSRV) and enzootic nasal tumor virus (ENTV), is responsible for their distinct low pH requirements for membrane fusion and infection. The Leu and Val residues are predicted to reside within the C-terminal heptad repeat (HR2) region of JSRV and ENTV Envs, particularly proximal to the hairpin turn of the putative six-helix bundle (6HB). Substitution of …


Hiv-1 Effects On Neuropsychological Performance In A Resource-Limited Country, Zambia, Gabriel Holguin, Mwanza Banda, Elizabeth J. Willen, Costantine Malama, Kaseya O. Chiyenu, Victor C. Mudenda, Charles Wood 2011 University of Nebraska-Lincoln

Hiv-1 Effects On Neuropsychological Performance In A Resource-Limited Country, Zambia, Gabriel Holguin, Mwanza Banda, Elizabeth J. Willen, Costantine Malama, Kaseya O. Chiyenu, Victor C. Mudenda, Charles Wood

Nebraska Center for Virology: Faculty Publications

Zambia has substantially been affected by the HIV/AIDS epidemic with prevalence rates at 14% in a population estimated at 12 million. Yet, the extent of HIV-associated neurocognitive disorders (HAND) in this population remains to be clearly understood. A series of culturally appropriate neuropsychological (NP) assessments [International HIV Dementia Scale (IHDS), Color Trails Test 1 and 2, Grooved pegboard Test, and Time Gait Test] were used to test the effects of HIV on NP performance of HIV seropositive and seronegative individuals. Twenty-two percent HIV positive individuals ARV naïve met the criteria for IHDS-defined NP impairment. Gender significantly influenced the performance on …


Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry 2011 University of Nebraska-Lincoln & Mayo Clinic, Rochester

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 …


Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry 2011 Mayo Graduate School, Rochester,

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …


Adventures In The Enormous: A 1.8 Million Clone Bac Library For The 21.7 Gb Genome Of Loblolly Pine, Zenaida Magbanua, Seval Ozkan, Benjamin Bartlett, Philippe Chouvarine, Christopher Saski, Aaron Siston, Richard Cronn, C Dana Nelson, Daniel Peterson 2011 Mississippi State University

Adventures In The Enormous: A 1.8 Million Clone Bac Library For The 21.7 Gb Genome Of Loblolly Pine, Zenaida Magbanua, Seval Ozkan, Benjamin Bartlett, Philippe Chouvarine, Christopher Saski, Aaron Siston, Richard Cronn, C Dana Nelson, Daniel Peterson

Publications

Loblolly pine (LP; Pinus taeda L.) is the most economically important tree in the U.S. and a cornerstone species in southeastern forests. However, genomics research on LP and other conifers has lagged behind studies on flowering plants due, in part, to the large size of conifer genomes. As a means to accelerate conifer genome research, we constructed a BAC library for the LP genotype 7-56. The LP BAC library consists of 1,824,768 individually-archived clones making it the largest single BAC library constructed to date, has a mean insert size of 96 kb, and affords 7.6X coverage of the 21.7 Gb …


Effects Of Restricting Energy During The Gilt Developmental Period On Growth And Reproduction Of Lines Differing In Lean Growth Rate: Responses In Feed Intake, Growth, And Age At Puberty, P. S. Miller, R. Moreno, R. K. Johnson 2011 University of Nebraska-Lincoln

Effects Of Restricting Energy During The Gilt Developmental Period On Growth And Reproduction Of Lines Differing In Lean Growth Rate: Responses In Feed Intake, Growth, And Age At Puberty, P. S. Miller, R. Moreno, R. K. Johnson

Department of Animal Science: Faculty Publications

The overall objective was to compare reproductive performance through 4 parities of gilts developed with ad libitum access to feed or with restriction of energy to 75% of ad libitum intake. Effects on growth and pubertal development are reported. The experiment was a 2 × 2 factorial with 661 gilts. One-half of the gilts (n = 330) were allowed ad libitum access to feed from weaning to breeding at 235 d of age (AL), and 331 littermates were developed with ad libitum access to feed to 123 d of age and then restricted to 75% of ad libitum intake to …


Synthetic Hype: A Skeptical View Of The Promise Of Synthetic Biology, Jonathan Kahn 2011 Mitchell Hamline School of Law

Synthetic Hype: A Skeptical View Of The Promise Of Synthetic Biology, Jonathan Kahn

Faculty Scholarship

This article urges a cautious approach to assessing the promises of synthetic biology based on broad political and economic concerns rather than technical ones. Specifically, I mark three related dynamics which place the current buzz around synthetic biology in a broader context. These dynamics are not necessarily distinctive to synthetic biology, but perhaps for that very reason, they may carry added weight. First, is the place of synthetic biology as the latest entry in the procession of what I call the “receding horizons of biotechnological promise.” Second, is the excitement generated by the related promise of finding seemingly direct technological …


A Parallel Graph Sampling Algorithm For Analyzing Gene Correlation Networks, Kathryn Dempsey Cooper, Kanimathi Duraisamy, Hesham Ali, Sanjukta Bhowmick 2011 University of Nebraska at Omaha

A Parallel Graph Sampling Algorithm For Analyzing Gene Correlation Networks, Kathryn Dempsey Cooper, Kanimathi Duraisamy, Hesham Ali, Sanjukta Bhowmick

Interdisciplinary Informatics Faculty Publications

Effcient analysis of complex networks is often a challenging task due to its large size and the noise inherent in the system. One popular method of overcoming this problem is through graph sampling, that is extracting a representative subgraph from the larger network. The accuracy of the sample is validated by comparing the combinatorial properties of the subgraph and the original network. However, there has been little study in comparing networks based on the applications that they represent. Furthermore, sampling methods are generally applied agnostically, without mapping to the requirements of the underlying analysis. In this paper,we introduce a parallel …


Role Of Hydrodynamic Behavior Of Dna Molecules In Dielectrophoretic Polarization Under The Action Of An Electric Field, Hui Zhao 2011 University of Nevada, Las Vegas

Role Of Hydrodynamic Behavior Of Dna Molecules In Dielectrophoretic Polarization Under The Action Of An Electric Field, Hui Zhao

Mechanical Engineering Faculty Research

A continuum model is developed to predict the dielectrophoretic polarizability of coiled DNA molecules under the action of an alternating current electric field. The model approximates the coiled DNA molecule as a charged porous spherical particle. The model explains the discrepancies among scaling laws of polarizability of different-sized DNA molecules with contour length and such discrepancies are attributed to different hydrodynamic behavior. With zero or one fitting parameter, theoretical predictions are in good agreement with various experimental data, even though in experiments there are some uncertainties in regard to certain parameters.


Characterization Of Cis-Regulatory Elements Controlling Repo Transcription In Drosophila Melanogaster, Robert Johnson 2011 University of Mississippi

Characterization Of Cis-Regulatory Elements Controlling Repo Transcription In Drosophila Melanogaster, Robert Johnson

Electronic Theses and Dissertations

The glial cells missing (gcm) gene has been identified as a "master regulator" of glial cell fate in the fruit fly Drosophila . However, the gcm gene is also expressed in and required for the development of larval macrophages and tendon cells, and lamina neurons in the adult CNS. Thus, the Gcm protein activates the transcription of different sets of genes in different developmental contexts. How the Gcm protein regulates these different outcomes is not known. My long-term goal is to identify proteins that collaborate with Gcm to promote the transcriptional activation of Gcm target genes specifically in glial cells, …


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