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Discovery Of Common Sequences Absent In The Human Reference Genome Using Pooled Samples From Next Generation Sequencing, Yu Liu, Mehmet Koyutürk, Sean Maxwell, Min Xiang, Martina Veigl, Richard S. Cooper, Bamidele O. Tayo, Li Li, Thomas Laframboise, Zhenghe Wang, Xiaofeng Zhu, Mark R. Chance Aug 2014

Discovery Of Common Sequences Absent In The Human Reference Genome Using Pooled Samples From Next Generation Sequencing, Yu Liu, Mehmet Koyutürk, Sean Maxwell, Min Xiang, Martina Veigl, Richard S. Cooper, Bamidele O. Tayo, Li Li, Thomas Laframboise, Zhenghe Wang, Xiaofeng Zhu, Mark R. Chance

Faculty Publications

Background: Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads …

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Synthesis And In Vitro Evaluation Of Bbb Permeability, Tumor Cell Uptake, And Cytotoxicity Of A Series Of Carboranylporphyrin Conjugates, N. V.S.Dinesh K. Bhupathiraju, Xiaoke Hu, Zehua Zhou, Frank R. Fronczek, Pierre Olivier Couraud, Ignacio A. Romero, Babette Weksler, M. Graça H. Vicente Aug 2014

Synthesis And In Vitro Evaluation Of Bbb Permeability, Tumor Cell Uptake, And Cytotoxicity Of A Series Of Carboranylporphyrin Conjugates, N. V.S.Dinesh K. Bhupathiraju, Xiaoke Hu, Zehua Zhou, Frank R. Fronczek, Pierre Olivier Couraud, Ignacio A. Romero, Babette Weksler, M. Graça H. Vicente

Faculty Publications

A series of tri[(p-carboranylmethylthio)tetrafluorophenyl]porphyrin conjugates of linear and branched polyamines, glucose, arginine, tri(ethylene glycol), and Tyr-d-Arg-Phe-β-Ala (YRFA) peptide were synthesized. These conjugates were investigated for their BBB permeability in human hCMEC/D3 brain endothelial cells, and their cytotoxicity and uptake were assessed using human glioma T98G cells. For comparison purposes, a symmetric tetra[(p- carboranylmethylthio)tetrafluorophenyl]porphyrin was also synthesized, and its crystal structure was obtained. All porphyrin conjugates show low dark cytotoxicity (IC50 > 400 μM) and low phototoxicity (IC 50 > 100 μM at 1.5 J/cm2) toward T98G cells. All conjugates were efficiently taken up by T98G cells, particularly the cationic polyamine and arginine …

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Carbon Dynamics On The Louisiana Continental Shelf And Cross-Shelf Feeding Of Hypoxia, Brian Fry, Dubravko Justic, Philip Riekenberg, Erick M. Swenson, R. Eugene Turner, Lixia Wang, Lora Pride, Nancy N. Rabalais, Janis C. Kurtz, John C. Lehrter, Michael C. Murrell, Elizabeth H. Shadwick, Brandon Boyd Aug 2014

Carbon Dynamics On The Louisiana Continental Shelf And Cross-Shelf Feeding Of Hypoxia, Brian Fry, Dubravko Justic, Philip Riekenberg, Erick M. Swenson, R. Eugene Turner, Lixia Wang, Lora Pride, Nancy N. Rabalais, Janis C. Kurtz, John C. Lehrter, Michael C. Murrell, Elizabeth H. Shadwick, Brandon Boyd

Faculty Publications

Large-scale hypoxia regularly develops during the summer on the Louisiana continental shelf. Traditionally, hypoxia has been linked to the vast winter and spring nutrient inputs from the Mississippi River and its distributary, the Atchafalaya River. However, recent studies indicate that much of the shelf ecosystem is heterotrophic. We used data from five late July shelfwide cruises from 2006 to 2010 to examine carbon and oxygen production and identify net autotrophic areas of phytoplankton growth on the Louisiana shelf. During these summer times of moderate river flows, shelfwide pH and particulate organic carbon (POC) consistently showed strong signals for net autotrophy …

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Advances In Gpcr Modeling Evaluated By The Gpcr Dock 2013 Assessment: Meeting New Challenges, Irina Kufareva, Vsevolod Katritch, Phil Biggin, Minsup Kim, Kichul Park, Sang Won Jung, Art E. Cho, Zara A. Sands, Liliana Ostopovici-Halip, Cristian G. Bologa, Christoffer Norn, Michal Brylinski, Jeffrey Skolnick, Henrik Keränen, Bart E. Lenselink, Gerard Van Westen, John P. Overington, Hugo Gutiérrez De Teráán, Vignir Isberg, Kimberley M. Fidom, Thomas M. Lehto, David E. Gloriam, Anirban Ghosh, Uddhavesh Sonavane, Rajendra Joshi, Jie Xia, Jui Hua Hsieh, Liangren Zhang, Xiang Simon Wang, Horst Vogel, Shuguang Yuan, X. Feng, M. Chen, J. Ambia Aug 2014

Advances In Gpcr Modeling Evaluated By The Gpcr Dock 2013 Assessment: Meeting New Challenges, Irina Kufareva, Vsevolod Katritch, Phil Biggin, Minsup Kim, Kichul Park, Sang Won Jung, Art E. Cho, Zara A. Sands, Liliana Ostopovici-Halip, Cristian G. Bologa, Christoffer Norn, Michal Brylinski, Jeffrey Skolnick, Henrik Keränen, Bart E. Lenselink, Gerard Van Westen, John P. Overington, Hugo Gutiérrez De Teráán, Vignir Isberg, Kimberley M. Fidom, Thomas M. Lehto, David E. Gloriam, Anirban Ghosh, Uddhavesh Sonavane, Rajendra Joshi, Jie Xia, Jui Hua Hsieh, Liangren Zhang, Xiang Simon Wang, Horst Vogel, Shuguang Yuan, X. Feng, M. Chen, J. Ambia

Faculty Publications

© 2014 Elsevier Ltd All rights reserved. Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock assessment was established to stimulate and monitor the progress in molecular modeling and ligand docking for GPCRs. The four targets in the present third assessment round presented new and diverse challenges for modelers, including prediction of allosteric ligand interaction and activation states in 5-hydroxytryptamine receptors 1B and 2B, and modeling by extremely …

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Nucleolar Stress With And Without P53, Allison James, Yubo Wang, Himanshu Raje, Raphyel Rosby, Patrick Dimario Aug 2014

Nucleolar Stress With And Without P53, Allison James, Yubo Wang, Himanshu Raje, Raphyel Rosby, Patrick Dimario

Faculty Publications

Averitable explosion of primary research papers within the past 10 years focuses on nucleolar and ribosomal stress, and for good reason: with ribosome biosynthesis consuming ∼80% of a cell’s energy, nearly all metabolic and signaling pathways lead ultimately to or from the nucleolus. We begin by describing p53 activation upon nucleolar stress resulting in cell cycle arrest or apoptosis. The significance of this mechanism cannot be understated, as oncologists are now inducing nucleolar stress strategically in cancer cells as a potential anti-cancer therapy. We also summarize the human ribosomopathies, syndromes in which ribosome biogenesis or function are impaired leading to …

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Review Of Particle Physics, K. A. Olive, K. Agashe, C. Amsler, M. Antonelli, J. F. Arguin, D. M. Asner, H. Baer, H. R. Band, R. M. Barnett, T. Basaglia, C. W. Bauer, J. J. Beatty, V. L. Belousov, J. Beringer, G. Bernardi, S. Bethke, H. Bichsel, O. Biebel, E. Blucher, S. Blusk, G. Brooijmans, O. Buchmueller, V. Burkert, M. A. Bychkov, R. N. Cahn, M. Carena, A. Ceccucci, A. Cerri, D. Chakraborty, M. C. Chen, R. S. Chivukula, K. Copie, G. Cowan Aug 2014

Review Of Particle Physics, K. A. Olive, K. Agashe, C. Amsler, M. Antonelli, J. F. Arguin, D. M. Asner, H. Baer, H. R. Band, R. M. Barnett, T. Basaglia, C. W. Bauer, J. J. Beatty, V. L. Belousov, J. Beringer, G. Bernardi, S. Bethke, H. Bichsel, O. Biebel, E. Blucher, S. Blusk, G. Brooijmans, O. Buchmueller, V. Burkert, M. A. Bychkov, R. N. Cahn, M. Carena, A. Ceccucci, A. Cerri, D. Chakraborty, M. C. Chen, R. S. Chivukula, K. Copie, G. Cowan

Faculty Publications

The Review summarizes much of particle physics and cosmology. Using data from previous editions, plus 3,283 new measurements from 899 papers, we list, evaluate, and average measured properties of gauge bosons and the recently discovered Higgs boson, leptons, quarks, mesons, and baryons. We summarize searches for hypothetical particles such as heavy neutrinos, supersymmetric and technicolor particles, axions, dark photons, etc. All the particle properties and search limits are listed in Summary Tables. We also give numerous tables, figures, formulae, and reviews of topics such as Supersymmetry, Extra Dimensions, Particle Detectors, Probability, and Statistics. Among the 112 reviews are many that …

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Cdk1 Promotes Cytokinesis In Fission Yeast Through Activation Of The Septation Initiation Network, Nicole Rachfall, Alyssa E. Johnson, Sapna Mehta, Jun Song Chen, Kathleen L. Gould Aug 2014

Cdk1 Promotes Cytokinesis In Fission Yeast Through Activation Of The Septation Initiation Network, Nicole Rachfall, Alyssa E. Johnson, Sapna Mehta, Jun Song Chen, Kathleen L. Gould

Faculty Publications

In Schizosaccharomyces pombe, late mitotic events are coordinated with cytokinesis by the septation initiation network (SIN), an essential spindle pole body (SPB)-associated kinase cascade, which controls the formation, maintenance, and constriction of the cytokinetic ring. It is not fully understood how SIN initiation is temporally regulated, but it depends on the activation of the GTPase Spg1, which is inhibited during interphase by the essential bipartite GTPase-activating protein Byr4-Cdc16. Cells are particularly sensitive to the modulation of Byr4, which undergoes cell cycle-dependent phosphorylation presumed to regulate its function. Polo-like kinase, which promotes SIN activation, is partially responsible for Byr4 phosphorylation. Here …

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Digital Anthropomorphic Phantoms Of Non-Rigid Human Respiratory And Voluntary Body Motion For Investigating Motion Correction In Emission Imaging, Arda Könik, Caitlin M. Connolly, Karen L. Johnson, Paul Dasari, Paul W. Segars, P. H. Pretorius, Clifford Lindsay, Joyoni Dey, Michael A. King Jul 2014

Digital Anthropomorphic Phantoms Of Non-Rigid Human Respiratory And Voluntary Body Motion For Investigating Motion Correction In Emission Imaging, Arda Könik, Caitlin M. Connolly, Karen L. Johnson, Paul Dasari, Paul W. Segars, P. H. Pretorius, Clifford Lindsay, Joyoni Dey, Michael A. King

Faculty Publications

The development of methods for correcting patient motion in emission tomography has been receiving increased attention. Often the performance of these methods is evaluated through simulations using digital anthropomorphic phantoms, such as the commonly used extended cardiac torso (XCAT) phantom, which models both respiratory and cardiac motion based on human studies. However, non-rigid body motion, which is frequently seen in clinical studies, is not present in the standard XCAT phantom. In addition, respiratory motion in the standard phantom is limited to a single generic trend. In this work, to obtain a more realistic representation of motion, we developed a series …

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Ligand-Binding Pocket Bridges Dna-Binding And Dimerization Domains Of The Urate-Responsive Marr Homologue Mftr From Burkholderia Thailandensis, Ashish Gupta, Anne Grove Jul 2014

Ligand-Binding Pocket Bridges Dna-Binding And Dimerization Domains Of The Urate-Responsive Marr Homologue Mftr From Burkholderia Thailandensis, Ashish Gupta, Anne Grove

Faculty Publications

Members of the multiple antibiotic resistance regulator (MarR) family often regulate gene activity by responding to a specific ligand. In the absence of ligand, most MarR proteins function as repressors, while ligand binding causes attenuated DNA binding and therefore increased gene expression. Previously, we have shown that urate is a ligand for MftR (major facilitator transport regulator), which is encoded by the soil bacterium Burkholderia thailandensis. We show here that both mftR and the divergently oriented gene mftP encoding a major facilitator transport protein are upregulated in the presence of urate. MftR binds two cognate sites in the mftR-mftP intergenic …

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Genetic Analysis And Prevalence Studies Of The Brp Exopolysaccharide Locus Of Vibrio Vulnificus, Katherine L. Garrison-Schilling, Zelam M. Kaluskar, Bliss Lambert, Gregg S. Pettis Jul 2014

Genetic Analysis And Prevalence Studies Of The Brp Exopolysaccharide Locus Of Vibrio Vulnificus, Katherine L. Garrison-Schilling, Zelam M. Kaluskar, Bliss Lambert, Gregg S. Pettis

Faculty Publications

Phase variation in the Gram-negative human pathogen Vibrio vulnificus involves three colonial morphotypes- smooth opaque colonies due to production of capsular polysaccharide (CPS), smooth translucent colonies as the result of little or no CPS expression, and rugose colonies due to production of a separate extracellular polysaccharide (EPS), which greatly enhances biofilm formation. Previously, it was shown that the brp locus, which consists of nine genes arranged as an operon, is up-regulated in rugose strains in a c-di-GMP-dependent manner, and that plasmid insertions into the locus resulted in loss of rugosity and efficient biofilm production. Here, we have used non-polar mutagenesis …

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High-Throughput Targeted Repeat Element Bisulfite Sequencing (Ht-Trebs): Genome-Wide Dna Methylation Analysis Of Iap Ltr Retrotransposon, Muhammad B. Ekram, Joomyeong Kim Jul 2014

High-Throughput Targeted Repeat Element Bisulfite Sequencing (Ht-Trebs): Genome-Wide Dna Methylation Analysis Of Iap Ltr Retrotransposon, Muhammad B. Ekram, Joomyeong Kim

Faculty Publications

In vertebrates, DNA methylation-mediated repression of retrotransposons is essential for the maintenance of genomic integrity. In the current study, we developed a technique termed HT-TREBS (High-Throughput Targeted Repeat Element Bisulfite Sequencing). This technique is designed to measure the DNA methylation levels of individual loci of any repeat families with next-generation sequencing approaches. To test the feasibility of HT-TREBS, we analyzed the DNA methylation levels of the IAP LTR family using a set of 12 different genomic DNA isolated from the brain, liver and kidney of 4 one-weekold littermates of the mouse strain C57BL/6N. This technique has successfully generated the CpG …

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4d Optimization Of Scanned Ion Beam Tracking Therapy For Moving Tumors, John Gordon Eley, Wayne David Newhauser, Robert Lüchtenborg, Christian Graeff, Christoph Bert Jul 2014

4d Optimization Of Scanned Ion Beam Tracking Therapy For Moving Tumors, John Gordon Eley, Wayne David Newhauser, Robert Lüchtenborg, Christian Graeff, Christoph Bert

Faculty Publications

Motion mitigation strategies are needed to fully realize the theoretical advantages of scanned ion beam therapy for patients with moving tumors. The purpose of this study was to determine whether a new four-dimensional (4D) optimization approach for scanned-ion-beam tracking could reduce dose to avoidance volumes near a moving target while maintaining target dose coverage, compared to an existing 3D-optimized beam tracking approach. We tested these approaches computationally using a simple 4D geometrical phantom and a complex anatomic phantom, that is, a 4D computed tomogram of the thorax of a lung cancer patient. We also validated our findings using measurements of …

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Chemicals Facilitating Reprogramming: Targeting The Sam Binding Site To Identify Novel Methyltransferase Inhibitors, Jeong Do Kim, Jong S. Rim, Robert B. Crochet, Yong Hwan Lee, Jaroslaw Staszkiewicz, Ru Gao, Kenneth J. Eilertsen Jul 2014

Chemicals Facilitating Reprogramming: Targeting The Sam Binding Site To Identify Novel Methyltransferase Inhibitors, Jeong Do Kim, Jong S. Rim, Robert B. Crochet, Yong Hwan Lee, Jaroslaw Staszkiewicz, Ru Gao, Kenneth J. Eilertsen

Faculty Publications

© 2014 John Wiley & Sons, Ltd. Reprogramming of somatic cells to a pluripotent state has been achieved by viral-mediated transduction of defined transcription factors. In order to achieve the goal of clinical application, it is necessary to overcome a variety of limitations, including poor reprogramming efficiencies and viral integration. One strategy is to identify small-molecule inhibitors that can improve reprogramming efficiency or replace defined transcription factors. Several reports have demonstrated that modulation of chromatin-modifying enzymes can significantly improve reprogramming efficiency. Key enzymes include DNA and histone methyltransferases, which utilize the cofactor S-adenosyl methionine (SAM) to transfer a methyl group. …

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Louisiana Agriculture Summer, 2014, Lsu Agcenter Jul 2014

Louisiana Agriculture Summer, 2014, Lsu Agcenter

Louisiana Agriculture

No abstract provided.

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Chronic Stress Alters Concentrations Of Corticosterone Receptors In A Tissue-Specific Manner In Wild House Sparrows (Passer Domesticus), Christine R. Lattin, L. Michael Romero Jul 2014

Chronic Stress Alters Concentrations Of Corticosterone Receptors In A Tissue-Specific Manner In Wild House Sparrows (Passer Domesticus), Christine R. Lattin, L. Michael Romero

Faculty Publications

© 2014. Published by The Company of Biologists Ltd. The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed …

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Human Genomic Regions With Exceptionally High Levels Of Population Differentiation Identified From 911 Whole-Genome Sequences, V. Colonna, Q. Ayub, Y. Chen, L. Pagani, P. Luisi, M. Pybus, E. Garrison, Y. Xue, C. Tyler-Smith, G. R. Abecasis, A. Auton, L. D. Brooks, M. A. Depristo, R. M. Durbin, R. E. Handsaker, H. M. Kang, G. T. Marth, Ga Mcvean, D. M. Altshuler, D. R. Bentley, A. Chakravarti, A. G. Clark, P. Donnelly, E. E. Eichler, P. Flicek, S. B. Gabriel, R. A. Gibbs, E. D. Green, M. E. Hurles, B. M. Knoppers, J. O. Korbel, E. S. Lander, C. Lee, H. Lehrach Jun 2014

Human Genomic Regions With Exceptionally High Levels Of Population Differentiation Identified From 911 Whole-Genome Sequences, V. Colonna, Q. Ayub, Y. Chen, L. Pagani, P. Luisi, M. Pybus, E. Garrison, Y. Xue, C. Tyler-Smith, G. R. Abecasis, A. Auton, L. D. Brooks, M. A. Depristo, R. M. Durbin, R. E. Handsaker, H. M. Kang, G. T. Marth, Ga Mcvean, D. M. Altshuler, D. R. Bentley, A. Chakravarti, A. G. Clark, P. Donnelly, E. E. Eichler, P. Flicek, S. B. Gabriel, R. A. Gibbs, E. D. Green, M. E. Hurles, B. M. Knoppers, J. O. Korbel, E. S. Lander, C. Lee, H. Lehrach

Faculty Publications

© 2014 Colonna et al. Background: Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. Results: We demonstrate that while sites with …

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Amino Acids In The Uterine Luminal Fluid Reflects The Temporal Changes In Transporter Expression In The Endometrium And Conceptus During Early Pregnancy In Cattle, Niamh Forde, Constantine A. Simintiras, Roger Sturmey, Solomon Mamo, Alan K. Kelly, Thomas E. Spencer, Fuller W. Bazer, Pat Lonergan Jun 2014

Amino Acids In The Uterine Luminal Fluid Reflects The Temporal Changes In Transporter Expression In The Endometrium And Conceptus During Early Pregnancy In Cattle, Niamh Forde, Constantine A. Simintiras, Roger Sturmey, Solomon Mamo, Alan K. Kelly, Thomas E. Spencer, Fuller W. Bazer, Pat Lonergan

Faculty Publications

In cattle, conceptus-maternal interactions are critical for the establishment and maintenance of pregnancy. A major component of this early interaction involves the transport of nutrients and secretion of key molecules by uterine epithelial cells to help support conceptus development during the peri-implantation period of pregnancy. Objectives were to: 1) analyze temporal changes in the amino acid (AA) content of uterine luminal fluid (ULF) during the bovine estrous cycle; 2) understand conceptus-induced alterations in AA content; 3) determine expression of AA transporters in the endometrium and conceptus; and 4) determine how these transporters are modulated by (Progesterone) P4. Concentrations of aspartic …

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Elaborate Visual And Acoustic Signals Evolve Independently In A Large, Phenotypically Diverse Radiation Of Songbirds, Nicholas A. Mason, Allison J. Shultz, Kevin J. Burns Jun 2014

Elaborate Visual And Acoustic Signals Evolve Independently In A Large, Phenotypically Diverse Radiation Of Songbirds, Nicholas A. Mason, Allison J. Shultz, Kevin J. Burns

Faculty Publications

The concept of a macroevolutionary trade-off among sexual signals has a storied history in evolutionary biology. Theory predicts that if multiple sexual signals are costly for males to produce or maintain and females prefer a single, sexually selected trait, then an inverse correlation between sexual signal elaborations is expected among species. However, empirical evidence for what has been termed the 'transfer hypothesis' is mixed, which may reflect different selective pressures among lineages, evolutionary covariates or methodological differences among studies. Here,we examine interspecific correlations between song and plumage elaboration in a phenotypically diverse, widespread radiation of songbirds, the tanagers. The tanagers …

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Convergent Evolution Of Aquatic Foraging In A New Genus And Species (Rodentia: Muridae) From Sulawesi Island, Indonesia, Kevin C. Rowe, Anang S. Achmadi, Jacob A. Esselstyn Jun 2014

Convergent Evolution Of Aquatic Foraging In A New Genus And Species (Rodentia: Muridae) From Sulawesi Island, Indonesia, Kevin C. Rowe, Anang S. Achmadi, Jacob A. Esselstyn

Faculty Publications

The island of Sulawesi, in Indonesia, lies at the crossroads of the Indo-Australian Archipelago and has remained isolated from the Asian (Sunda) and Australian (Sahul) continental shelves for at least the last 10 million years. Of the 50 native species of rodents on Sulawesi, all are endemic and represent the evolution of a variety of ecological and morphological forms within the Muridae and Sciuridae. Carnivorous rodents have evolved, perhaps independently, in Muridae from the Philippines, Sulawesi, and Sahul, but semi-aquatic murids are only known from Sahul. Here we describe a new genus and species of insectivorous water rat from Sulawesi. …

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Integrating Sequence And Array Data To Create An Improved 1000 Genomes Project Haplotype Reference Panel, Olivier Delaneau, Jonathan Marchini, Gil A. Mcveanh, Peter Donnelly, Gerton Lunter, Jonathan L. Marchini, Simon Myers, Anjali Gupta-Hinch, Zamin Iqbal, Iain Mathieson, Andy Rimmer, Dionysia K. Xifara, Angeliki Kerasidou, Claire Churchhouse, David M. Altshuler, Stacey B. Gabriel, Eric S. Lander, Namrata Gupta, Mark J. Daly, Mark A. Depristo, Eric Banks, Gaurav Bhatia, Mauricio O. Carneiro, Guillermo Del Angel, Giulio Genovese, Robert E. Handsaker, Chris Hartl, Steven A. Mccarroll, James C. Nemesh, Ryan E. Poplin, Stephen F. Schaffner, Khalid Shakir, Pardis C. Sabeti, Sharon R. Grossman Jun 2014

Integrating Sequence And Array Data To Create An Improved 1000 Genomes Project Haplotype Reference Panel, Olivier Delaneau, Jonathan Marchini, Gil A. Mcveanh, Peter Donnelly, Gerton Lunter, Jonathan L. Marchini, Simon Myers, Anjali Gupta-Hinch, Zamin Iqbal, Iain Mathieson, Andy Rimmer, Dionysia K. Xifara, Angeliki Kerasidou, Claire Churchhouse, David M. Altshuler, Stacey B. Gabriel, Eric S. Lander, Namrata Gupta, Mark J. Daly, Mark A. Depristo, Eric Banks, Gaurav Bhatia, Mauricio O. Carneiro, Guillermo Del Angel, Giulio Genovese, Robert E. Handsaker, Chris Hartl, Steven A. Mccarroll, James C. Nemesh, Ryan E. Poplin, Stephen F. Schaffner, Khalid Shakir, Pardis C. Sabeti, Sharon R. Grossman

Faculty Publications

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for …

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Artemisia Scoparia Enhances Adipocyte Development And Endocrine Function In Vitro And Enhances Insulin Action In Vivo, Allison J. Richard, Scott Fuller, Veaceslav Fedorcenco, Robbie Beyl, Thomas P. Burris, Randall Mynatt, David M. Ribnicky, Jacqueline M. Stephens Jun 2014

Artemisia Scoparia Enhances Adipocyte Development And Endocrine Function In Vitro And Enhances Insulin Action In Vivo, Allison J. Richard, Scott Fuller, Veaceslav Fedorcenco, Robbie Beyl, Thomas P. Burris, Randall Mynatt, David M. Ribnicky, Jacqueline M. Stephens

Faculty Publications

Background: Failure of adipocytes to expand during periods of energy excess can result in undesirable metabolic consequences such as ectopic fat accumulation and insulin resistance. Blinded screening studies have indicated that Artemisia scoparia (SCO) extracts can enhance adipocyte differentiation and lipid accumulation in cultured adipocytes. The present study tested the hypothesis that SCO treatment modulates fat cell development and function in vitro and insulin sensitivity in adipose tissue in vivo. Methods: In vitro experiments utilized a Gal4-PPARγ ligand binding domain (LBD) fusion protein-luciferase reporter assay to examine PPARγ activation. To investigate the ability of SCO to modulate adipogenesis and mature …

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Synthesis, Spectroscopic, And Cellular Properties Of Α-Pegylated Cis-A2B2- And A3B-Types Znpcs, Benson G. Ongarora, Zehua Zhou, Elizabeth A. Okoth, Igor Kolesnichenko, Kevin M. Smith, M. Graça H. Vicente Jun 2014

Synthesis, Spectroscopic, And Cellular Properties Of Α-Pegylated Cis-A2B2- And A3B-Types Znpcs, Benson G. Ongarora, Zehua Zhou, Elizabeth A. Okoth, Igor Kolesnichenko, Kevin M. Smith, M. Graça H. Vicente

Faculty Publications

© 2014 World Scientific Publishing Company. A series of pegylated cis-A2B2- or A3B-type ZnPcs, substituted on the α-positions with tri(ethylene glycol) and hydroxyl groups, were synthesized from a new bis-phthalonitrile. A clamshell-type bis-phthalocyanine was also obtained as a byproduct. The hydroxyl group of one ZnPc was alkylated with 3-dimethylaminopropyl chloride to afford a pegylated ZnPc functionalized with an amine group. All mononuclear ZnPcs were soluble in polar organic solvents, showed intense Q absorptions in DMF, and had fluorescence quantum yields in the range 0.10-0.23. The clamshell-type bis-phthalocyanine adopts mainly open shell conformations in DMF, and closed clamshell conformations in chloroform. …

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Environmentally Persistent Free Radicals Inhibit Cytochrome P450 Activity In Rat Liver Microsomes, James R. Reed, George F. Cawley, Taylor G. Ardoin, Barry Dellinger, Slawomir M. Lomnicki, Farhana Hasan, Lucy W. Kiruri, Wayne L. Backes Jun 2014

Environmentally Persistent Free Radicals Inhibit Cytochrome P450 Activity In Rat Liver Microsomes, James R. Reed, George F. Cawley, Taylor G. Ardoin, Barry Dellinger, Slawomir M. Lomnicki, Farhana Hasan, Lucy W. Kiruri, Wayne L. Backes

Faculty Publications

Combustion processes generate particulate matter that affects human health. When incineration fuels include components that are highly enriched in aromatic hydrocarbons (especially halogenated varieties) and redox-active metals, ultrafine particulate matter containing air-stable, environmentally persistent free radicals (EPFRs) is generated. The exposure to fine EPFRs (less than 2.5. μm in diameter) has been shown to negatively influence pulmonary and cardiovascular functions in living organisms. The goal of this study was to determine if these EPFRs have a direct effect on cytochrome P450 function. This was accomplished by direct addition of the EPFRs to rat liver microsomal preparations and measurement of several …

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Hurricane Activity And The Large-Scale Pattern Of Spread Of An Invasive Plant Species, Ganesh P. Bhattarai, James T. Cronin May 2014

Hurricane Activity And The Large-Scale Pattern Of Spread Of An Invasive Plant Species, Ganesh P. Bhattarai, James T. Cronin

Faculty Publications

Disturbances are a primary facilitator of the growth and spread of invasive species. However, the effects of large-scale disturbances, such as hurricanes and tropical storms, on the broad geographic patterns of invasive species growth and spread have not been investigated. We used historical aerial imagery to determine the growth rate of invasive Phragmites australis patches in wetlands along the Atlantic and Gulf Coasts of the United States. These were relatively undisturbed wetlands where P. australis had room for unrestricted growth. Over the past several decades, invasive P. australis stands expanded in size by 6-35% per year. Based on tropical storm …

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Detection And Cellular Imaging Of Human Cancer Enzyme Using A Turn-On, Wavelength-Shiftable, Self-Immolative Profluorophore, Suraj U. Hettiarachchi, Bijeta Prasai, Robin L. Mccarley May 2014

Detection And Cellular Imaging Of Human Cancer Enzyme Using A Turn-On, Wavelength-Shiftable, Self-Immolative Profluorophore, Suraj U. Hettiarachchi, Bijeta Prasai, Robin L. Mccarley

Faculty Publications

A frontier area in the development of activatable (turn-on) fluorescence-based probes is that concerned with rapid and selective stimulus triggering of probe activation so as to allow for biomarker identification and cellular imaging. The work here is concerned with a cloaked fluorophore composed of a reporter whose fluorescence is efficiently quenched by it being bound to an activatable trigger group through a novel self-immolative linker. Highly selective and rapid activation of the trigger group is achieved by chemical and enzymatic means that result in activated trigger group detachment from the self-immolative linker, with the latter subsequently cleaved from the reporter …

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Amplification Of Angular Rotations Using Weak Measurements, Omar S. Magaña-Loaiza, Mohammad Mirhosseini, Brandon Rodenburg, Robert W. Boyd May 2014

Amplification Of Angular Rotations Using Weak Measurements, Omar S. Magaña-Loaiza, Mohammad Mirhosseini, Brandon Rodenburg, Robert W. Boyd

Faculty Publications

We present a weak measurement protocol that permits a sensitive estimation of angular rotations based on the concept of weak-value amplification. The shift in the state of a pointer, in both angular position and the conjugate orbital angular momentum bases, is used to estimate angular rotations. This is done by an amplification of both the real and imaginary parts of the weak-value of a polarization operator that has been coupled to the pointer, which is a spatial mode, via a spin-orbit coupling. Our experiment demonstrates the first realization of weak-value amplification in the azimuthal degree of freedom. We have achieved …

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Do The Beaf Insulator Proteins Regulate Genes Involved In Cell Polarity And Neoplastic Growth?, Craig M. Hart May 2014

Do The Beaf Insulator Proteins Regulate Genes Involved In Cell Polarity And Neoplastic Growth?, Craig M. Hart

Faculty Publications

It was reported that a chromosome with the BEAFNP6377 (NP6377) allele leads to a loss of cell polarity and neoplastic growth in Drosophila melanogaster when homozygous (Gurudatta et al., 2012). We had previously generated the BEAFAB-KO (AB-KO) allele by homologous recombination and did not note these phenotypes (Roy et al., 2007). Both alleles are null mutations. It was unclear why two null alleles of the same gene would give different phenotypes. To resolve this, we performed genetic tests to explore the possibility that the chromosome with the NP6377 allele contained other, second site mutations that might account for the different …

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Social Opportunity Rapidly Regulates Expression Of Crf And Crf Receptors In The Brain During Social Ascent Of A Teleost Fish, Astatotilapia Burtoni, Russ E. Carpenter, Karen P. Maruska, Lisa Becker, Russell D. Fernald May 2014

Social Opportunity Rapidly Regulates Expression Of Crf And Crf Receptors In The Brain During Social Ascent Of A Teleost Fish, Astatotilapia Burtoni, Russ E. Carpenter, Karen P. Maruska, Lisa Becker, Russell D. Fernald

Faculty Publications

In social animals, hierarchical rank governs food availability, territorial rights and breeding access. Rank order can change rapidly and typically depends on dynamic aggressive interactions. Since the neuromodulator corticotrophin releasing factor (CRF) integrates internal and external cues to regulate the hypothalamic-pituitary adrenal (HPA) axis, we analyzed the CRF system during social encounters related to status. We used a particularly suitable animal model, African cichlid fish, Astatotilapia burtoni, whose social status regulates reproduction. When presented with an opportunity to rise in rank, subordinate A. burtoni males rapidly change coloration, behavior, and their physiology to support a new role as dominant, reproductively …

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Comparative Systems Biology Reveals Allelic Variation Modulating Tocochromanol Profiles In Barley (Hordeum Vulgare L.), Rebekah E. Oliver, Emir Islamovic, Donald E. Obert, Mitchell L. Wise, Lauri L. Herrin, An Hang, Stephen A. Harrison, Amir Ibrahim, Juliet M. Marshall, Kelci J. Miclaus, Gerard R. Lazo, Gongshe Hu, Eric W. Jackson May 2014

Comparative Systems Biology Reveals Allelic Variation Modulating Tocochromanol Profiles In Barley (Hordeum Vulgare L.), Rebekah E. Oliver, Emir Islamovic, Donald E. Obert, Mitchell L. Wise, Lauri L. Herrin, An Hang, Stephen A. Harrison, Amir Ibrahim, Juliet M. Marshall, Kelci J. Miclaus, Gerard R. Lazo, Gongshe Hu, Eric W. Jackson

Faculty Publications

Tocochromanols are recognized for nutritional content, plant stress response, and seed longevity. Here we present a systems biological approach to characterize and develop predictive assays for genes affecting tocochromanol variation in barley. Major QTL, detected in three regions of a SNP linkage map, affected multiple tocochromanol forms. Candidate genes were identified through barley/rice orthology and sequenced in genotypes with disparate tocochromanol profiles. Gene-specific markers, designed based on observed polymorphism, mapped to the originating QTL, increasing R2 values at the respective loci. Polymorphism within promoter regions corresponded to motifs known to influence gene expression. Quantitative PCR analysis revealed a trend of …

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Horizontal Transfer Of An Adaptive Chimeric Photoreceptor From Bryophytes To Ferns, Fay Wei Li, Juan Carlos Villarreal, Steven Kelly, Carl J. Rothfels, Michael Melkonian, Eftychios Frangedakis, Markus Ruhsam, Erin M. Sigel, Joshua P. Der, Jarmila Pittermann, Dylan O. Burge, Lisa Pokorny, Anders Larsson, Tao Chen, Stina Weststrand, Philip Thomas, Eric Carpenter, Yong Zhang, Zhijian Tian, Li Chen, Zhixiang Yan, Ying Zhu, Xiao Sun, Jun Wang, Dennis W. Stevenson, Barbara J. Crandall-Stotler, A. Jonathan Shaw, Michael K. Deyholos, Douglas E. Soltis, Sean W. Graham, Michael D. Windham, Jane A. Langdale, Gane Ka Shu Wong May 2014

Horizontal Transfer Of An Adaptive Chimeric Photoreceptor From Bryophytes To Ferns, Fay Wei Li, Juan Carlos Villarreal, Steven Kelly, Carl J. Rothfels, Michael Melkonian, Eftychios Frangedakis, Markus Ruhsam, Erin M. Sigel, Joshua P. Der, Jarmila Pittermann, Dylan O. Burge, Lisa Pokorny, Anders Larsson, Tao Chen, Stina Weststrand, Philip Thomas, Eric Carpenter, Yong Zhang, Zhijian Tian, Li Chen, Zhixiang Yan, Ying Zhu, Xiao Sun, Jun Wang, Dennis W. Stevenson, Barbara J. Crandall-Stotler, A. Jonathan Shaw, Michael K. Deyholos, Douglas E. Soltis, Sean W. Graham, Michael D. Windham, Jane A. Langdale, Gane Ka Shu Wong

Faculty Publications

Ferns are well known for their shade-dwelling habits. Their ability to thrive under low-light conditions has been linked to the evolution of a novel chimeric photoreceptor-neochrome-that fuses red-sensing phytochrome and blue-sensing phototropin modules into a single gene, thereby optimizing phototropic responses. Despite being implicated in facilitating the diversification of modern ferns, the origin of neochrome has remained a mystery. We present evidence for neochrome in hornworts (a bryophyte lineage) and demonstrate that ferns acquired neochrome from hornworts via horizontal gene transfer (HGT). Fern neochromes are nested within hornwort neochromes in our large-scale phylogenetic reconstructions of phototropin and phytochrome gene families. …

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