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Insights Into Diterpene Cyclization From Structure Of Bifunctional Abietadiene Synthase From Abies Grandis, Ke Zhou, Yang Gao, Julie A. Hoy, Francis M. Mann, Richard B. Honzatko, Reuben J. Peters 2017 Iowa State University

Insights Into Diterpene Cyclization From Structure Of Bifunctional Abietadiene Synthase From Abies Grandis, Ke Zhou, Yang Gao, Julie A. Hoy, Francis M. Mann, Richard B. Honzatko, Reuben J. Peters

Reuben J. Peters

Abietadiene synthase from Abies grandis (AgAS) is a model system for diterpene synthase activity, catalyzing class I (ionization-initiated) and class II (protonation-initiated) cyclization reactions. Reported here is the crystal structure of AgAS at 2.3 Å resolution and molecular dynamics simulations of that structure with and without active site ligands. AgAS has three domains (α, β, and γ). The class I active site is within the C-terminal α domain, and the class II active site is between the N-terminal γ and β domains. The domain organization resembles that of monofunctional diterpene synthases and is consistent with proposed evolutionary origins of ...


Diterpene Cyclases And The Nature Of The Isoprene Fold, Rong Cao, Yonghui Zhang, Francis M. Mann, Cancan Huang, Dushyant Mukkamala, Michael P. Hudock, Matthew Mead, Sladjana Prisic, Ke Wang, Fu-Yang Lin, Ting-Kai Chang, Reuben Peters, Eric Oldfield 2017 University of Illinois at Urbana-Champaign

Diterpene Cyclases And The Nature Of The Isoprene Fold, Rong Cao, Yonghui Zhang, Francis M. Mann, Cancan Huang, Dushyant Mukkamala, Michael P. Hudock, Matthew Mead, Sladjana Prisic, Ke Wang, Fu-Yang Lin, Ting-Kai Chang, Reuben Peters, Eric Oldfield

Reuben J. Peters

The structures and mechanism of action of many terpene cyclases are known, but there are no structures of diterpene cyclases. Here, we propose structural models based on bioinformatics, sitedirected mutagenesis, domain swapping, enzyme inhibition and spectroscopy that help explain the nature of diterpene cyclase structure, function, and evolution. Bacterial diterpene cyclases contain ~20 α-helices and the same conserved “QW” and DxDD motifs as in triterpene cyclases, indicating the presence of a βγ barrel structure. Plant diterpene cyclases have a similar catalytic motif and βγ-domain structure together with a third, α-domain, forming an αβγ structure, and in H+-initiated cyclases, there ...


Using Phylogenetically-Informed Annotation (Pia) To Search For Light-Interacting Genes In Transcriptomes From Non-Model Organisms, Daniel I. Speiser, M. Sabrina Pankey, Alexander K. Zaharoff, Barbara A. Battelle, Heather D. Bracken-Grissom, Jesse W. Breinholt, Seth M. Bybee, Thomas W. Cronin, Anders Garm, Annie R. Lindgren, Nipam H. Patel, Megan L. Porter, Meredith E. Protas, Anja S. Rivera, Jeanne M. Serb, Kirk S. Zigler, Keith A. Crandall, Todd H. Oakley 2017 Department of Ecology, Evolution, and Marine Biology, University of California Santa Barbara

Using Phylogenetically-Informed Annotation (Pia) To Search For Light-Interacting Genes In Transcriptomes From Non-Model Organisms, Daniel I. Speiser, M. Sabrina Pankey, Alexander K. Zaharoff, Barbara A. Battelle, Heather D. Bracken-Grissom, Jesse W. Breinholt, Seth M. Bybee, Thomas W. Cronin, Anders Garm, Annie R. Lindgren, Nipam H. Patel, Megan L. Porter, Meredith E. Protas, Anja S. Rivera, Jeanne M. Serb, Kirk S. Zigler, Keith A. Crandall, Todd H. Oakley

Jeanne M Serb

Background: Tools for high throughput sequencing and de novo assembly make the analysis of transcriptomes (i.e. the suite of genes expressed in a tissue) feasible for almost any organism. Yet a challenge for biologists is that it can be difficult to assign identities to gene sequences, especially from non-model organisms. Phylogenetic analyses are one useful method for assigning identities to these sequences, but such methods tend to be time-consuming because of the need to re-calculate trees for every gene of interest and each time a new data set is analyzed. In response, we employed existing tools for phylogenetic analysis ...


Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew McDermut 2017 Washington University in St. Louis

Isolation And Comparative Genomic Analysis Of Final Third Of Satis Genome, Kelly Hartigan, Nicole Curnutt, Matthew Mcdermut

Undergraduate Research Symposium Posters

A highly novel Streptomyces phage, Satis, was isolated from a direct environmental sample collected from outside Danforth House on the Washington University campus. Satis infects bacterial species Streptomyces lividans producing pinpoint, cloudy plaques less than 1mm in diameter. Electron microscope data shows rare atypical physical features. Rather than the common octahedral capsid shape, Satis has a prolate head with visible cross-linked hexagonal protein structure and average measurements of 285 nm by 47 nm with a long, flexible tail measuring 268 nm. Upon sequencing, it was found that Satis contains the longest phage genome discovered to date through the SEA-PHAGE program ...


Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis 2017 Clark Atlanta University

Characterization Of Zic2 As An Oncoprotein In Prostate Cancer, Keira C. Davis

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The field of prostate cancer research is in need of biological markers that predict which cancers do not need treatment, those that can be treated successfully with a localized treatment and more specific cases in which patients are likely to have an aggressive form of cancer that will require more aggressive surgical and chemotherapeutic treatments. ZIC2 is one of five members of a family of proteins that play critical roles in neural crest and mesoderm growth in normal embryonic brain development and in the adult cerebellum of vertebrates. Found throughout the animal kingdom, ZIC1-5 genes encode five distinct ZIC proteins ...


Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot 2017 The University of Western Ontario

Evolutionary Genetic Aspects Of Host Association In Generalist Ectoparasites, Benoit Talbot

Electronic Thesis and Dissertation Repository

Despite the use of the host for dispersal by most parasite species, the extremely loose relationship typical between highly mobile hosts and generalist ectoparasites may lead to very different gene flow patterns between the two, leading in turn to different spatial genetic structure, and potentially different demographic history. I examined how similar gene flow patterns are between Cimex adjunctus, a generalist ectoparasite of bats present throughout North America, and two of its key bat hosts. I first analyzed the continent-scale genetic structure and demographic history of C. adjunctus and compared it to that of two of its hosts, the little ...


Can Cone Signals In The Wild Be Predicted From The Past?, David H. Foster, Iván Marín-Franch 2017 University of Manchester, UK

Can Cone Signals In The Wild Be Predicted From The Past?, David H. Foster, Iván Marín-Franch

MODVIS Workshop

In the natural world, the past is usually a good guide to the future. If light from the sun and sky is blue earlier in the day and yellow now, then it is likely to be more yellow later, as the sun's elevation decreases. But is the light reflected from a scene into the eye as predictable as the light incident upon the scene, especially when lighting changes are not just spectral but include changes in local shadows and mutual reflections? The aim of this work was to test the predictability of cone photoreceptor signals in the wild over ...


Generation Of Tandem Direct Duplications By Reversed-Ends Transposition Of Maize Ac Elements, Jianbo Zhang, Tao Zuo, Thomas A. Peterson 2017 Iowa State University

Generation Of Tandem Direct Duplications By Reversed-Ends Transposition Of Maize Ac Elements, Jianbo Zhang, Tao Zuo, Thomas A. Peterson

Thomas Peterson

Tandem direct duplications are a common feature of the genomes of eukaryotes ranging from yeast to human, where they comprise a significant fraction of copy number variations. The prevailing model for the formation of tandem direct duplications is non-allelic homologous recombination (NAHR). Here we report the isolation of a series of duplications and reciprocal deletions isolated de novo from a maize allele containing two Class II Ac/Ds transposons. The duplication/deletion structures suggest that they were generated by alternative transposition reactions involving the termini of two nearby transposable elements. The deletion/duplication breakpoint junctions contain 8 bp target site ...


Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang 2017 Washington University in St. Louis

Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang

Arts & Sciences Electronic Theses and Dissertations

Cell identity and function rely on intricately controlled programs of gene regulation, alterations of which underlie many diseases, including cancer. Epigenetic analyses of normal and diseased cells have started to elucidate different facets of epigenetic mechanisms for gene regulation. These include changes in nucleosome density, histone modifications, factor binding and chromosomal architecture. All of these aspects contribute to the activities of regulatory elements conferring promoter, enhancer and insulator functions and the cis-regulatory circuits formed by these elements. Despite this progress, an urgent need remains to profile these features and to study how they cooperatively function in normal and pathogenic settings ...


Complex Dna Nanostructures From Oligonucleotide Ensembles, Divita Mathur, Eric R. Henderson 2017 Iowa State University

Complex Dna Nanostructures From Oligonucleotide Ensembles, Divita Mathur, Eric R. Henderson

Eric Henderson

The first synthetic DNA nanostructures were created by self-assembly of a small number of oligonucleotides. Introduction of the DNA origami method provided a new paradigm for designing and creating two- and three-dimensional DNA nanostructures by folding a large single-stranded DNA and ‘stapling’ it together with a library of oligonucleotides. Despite its power and wide-ranging implementation, the DNA origami technique suffers from some limitations. Foremost among these is the limited number of useful single-stranded scaffolds of biological origin. This report describes a new approach to creating large DNA nanostructures exclusively from synthetic oligonucleotides. The essence of this approach is to replace ...


Programmable Dna Nanosystem For Molecular Interrogation, Davita Mathur, Eric R. Henderson 2017 United States Naval Research Laboratory

Programmable Dna Nanosystem For Molecular Interrogation, Davita Mathur, Eric R. Henderson

Eric Henderson

We describe a self-assembling DNA-based nanosystem for interrogating molecular interactions. The nanosystem contains a rigid supporting dumbbell-shaped frame, a cylindrical central core, and a mobile ring that is coaxial with the core. Motion of the ring is influenced by several control elements whose force-generating capability is based on the transition of single-stranded DNA to double-stranded DNA. These forces can be directed to act in opposition to adhesive forces between the ring and the frame thereby providing a mechanism for molecular detection and interrogation at the ring-frame interface. As proof of principle we use this system to evaluate base stacking adhesion ...


A Novel Method For Quantifying Spatial Patterns In Plants, Logan H. George 2017 College of William and Mary

A Novel Method For Quantifying Spatial Patterns In Plants, Logan H. George

Undergraduate Honors Theses

Color patterns are found in a plethora of organisms, from vertebrates to flowering plants. While many studies have examined the mechanisms that produce these diverse patterns in animals, little research has investigated the mechanisms by which plants create color patterns. The conclusions drawn from animal studies may not accurately translate to plants due to early divergence in the evolution of life. Characterization of plant patterning mechanisms would have widespread impacts on developmental and evolutionary biology. To unravel the mystery behind pattern formation, we suggest an experimental framework to understand pattern evolution and development at a phenotypic, genotypic, and quantitative level ...


Basic Science To Clinical Research: Segmentation Of Ultrasound And Modelling In Clinical Informatics, Ali K. Hamou 2017 The University of Western Ontario

Basic Science To Clinical Research: Segmentation Of Ultrasound And Modelling In Clinical Informatics, Ali K. Hamou

Electronic Thesis and Dissertation Repository

The world of basic science is a world of minutia; it boils down to improving even a fraction of a percent over the baseline standard. It is a domain of peer reviewed fractions of seconds and the world of squeezing every last ounce of efficiency from a processor, a storage medium, or an algorithm. The field of health data is based on extracting knowledge from segments of data that may improve some clinical process or practice guideline to improve the time and quality of care. Clinical informatics and knowledge translation provide this information in order to reveal insights to the ...


Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto 2017 George Washington University

Mutations In Braf Are Associated With Higher Levels Of Immune Infiltrates In Microsatellite-Stable Colon Cancer, Jake Rubin, Eduard Porta Parto

GW Research Days 2016 - Present

While BRAF is among the most well-established oncogenes in human cancers, more recently it has garnered attention for its role in suppressing antitumor immunity, especially in melanoma. Because tumor-infiltrating lymphocyte (TIL) density is strongly prognostic in colorectal cancer (CRC)7, we decided to investigate the connection between TIL density and the BRAF-activating V600E mutation in CRC.

We used ESTIMATE to quantify immune infiltrate in samples from the TCGA colon adenocarcinoma (COAD) dataset (n = 216). This is an algorithm that uses the gene-expression signature of 141 immune-related genes to infer the presence of immune cells in the tumor infiltrate. COAD samples ...


Analysis Of Hiv-1 Quasispecies Sequences Generated By High Throughput Sequencing (Hts) Using Hive, Naila Gulzar, Bhavna Hora, Konstantinos Karagiannis, Krista Smith, Feng Gao, Raja Mazumder 2017 George Washington University

Analysis Of Hiv-1 Quasispecies Sequences Generated By High Throughput Sequencing (Hts) Using Hive, Naila Gulzar, Bhavna Hora, Konstantinos Karagiannis, Krista Smith, Feng Gao, Raja Mazumder

GW Research Days 2016 - Present

The high level of genetic variability of Human Immunodeficiency Virus type 1 (HIV-1) is caused by the low fidelity of its replication machinery. This leads to evolution of swarm-like viral populations often described as quasispecies. High throughput sequencing (HTS) technology provides higher resolution over Sanger sequencing, enabling detection of low frequency variant genomes. However, quasispecies analysis is still a challenge due to the systematic noise, introduced by HTS technology. This leads to the increase in type I errors (also known as false positives) and the underlying genetic diversity, which can lead to mathematically insolvable type II errors (also known as ...


Eassistant: Cognitive Assistance For Identification And Auto-Triage Of Actionable Conversations, Hamid R. Motahari Nezhad, Kalpa Gunaratna, Juan Cappi 2017 Wright State University - Main Campus

Eassistant: Cognitive Assistance For Identification And Auto-Triage Of Actionable Conversations, Hamid R. Motahari Nezhad, Kalpa Gunaratna, Juan Cappi

Kno.e.sis Publications

The browser and screen have been the main user interfaces of the Web and mobile apps. The notification mechanism is an evolution in the user interaction paradigm by keeping users updated without checking applications. Conversational agents are posed to be the next revolution in user interaction paradigms. However, without intelligence on the triage of content served by the interaction and content differentiation in applications, interaction paradigms may still place the burden of information overload on users. In this paper, we focus on the problem of intelligent identification of actionable information in the content served by applications, and in particular in ...


A Proposed Frequency-Based Feature Selection Method For Cancer Classification, Yi Pan 2017 Western Kentucky University

A Proposed Frequency-Based Feature Selection Method For Cancer Classification, Yi Pan

Masters Theses & Specialist Projects

Feature selection method is becoming an essential procedure in data preprocessing step. The feature selection problem can affect the efficiency and accuracy of classification models. Therefore, it also relates to whether a classification model can have a reliable performance. In this study, we compared an original feature selection method and a proposed frequency-based feature selection method with four classification models and three filter-based ranking techniques using a cancer dataset. The proposed method was implemented in WEKA which is an open source software. The performance is evaluated by two evaluation methods: Recall and Receiver Operating Characteristic (ROC). Finally, we found the ...


A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers 2017 Old Dominion University

A Balanced Approach To Adaptive Probability Density Estimation, Julio Kovacs, Cailee Helmick, Willy Wriggers

Mechanical & Aerospace Engineering Faculty Publications

Our development of a Fast (Mutual) Information Matching (FIM) of molecular dynamics time series data led us to the general problem of how to accurately estimate the probability density function of a random variable, especially in cases of very uneven samples. Here, we propose a novel Balanced Adaptive Density Estimation (BADE) method that effectively optimizes the amount of smoothing at each point. To do this, BADE relies on an efficient nearest-neighbor search which results in good scaling for large data sizes. Our tests on simulated data show that BADE exhibits equal or better accuracy than existing methods, and visual tests ...


Exploring The Use Of Free Bioinformatics Modules In An Introductory Biochemistry Course, Charlsey Dodgen, Uzezi Uwerosuo, ChulHee Kang, Cathy Lee 2017 University of Maryland

Exploring The Use Of Free Bioinformatics Modules In An Introductory Biochemistry Course, Charlsey Dodgen, Uzezi Uwerosuo, Chulhee Kang, Cathy Lee

Georgia Journal of Science

Although bioinformatics, the use of computational science to study biology, has become imperative in many areas of the biological sciences and related career paths, introductory biochemistry courses may disregard practical knowledge on bioinformatics. For this reason, we merged a hands-on activity module into an undergraduate biochemistry course in two ways. First, we incorporated bioinformatics modules for building phylogenetic trees by aligning the active sites of 10 chosen related α-amylase enzymes using freely available data. Secondly, we chose three of those 10 α-amylase enzymes to compare the 3D structure of their active sites. This module gives the students an opportunity to ...


Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey 2017 Maseno University

Human And Epstein-Barr Virus Mirna Profiling As Predictive Biomarkers For Endemic Burkitt Lymphoma, Cliff I. Oduor, Mercedeh Movassagh, Yasin Kaymaz, Kiprotich Chelimo, Juliana A. Otieno, John M. Ong'echa, Ann M. Moormann, Jeffrey A. Bailey

University of Massachusetts Medical School Faculty Publications

Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep ...


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