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Infectious Disease And The Diversification Of The Human Genome, Jessica F. Brinkworth 2017 University of Illinois Urbana-Champaign

Infectious Disease And The Diversification Of The Human Genome, Jessica F. Brinkworth

Human Biology Open Access Pre-Prints

The human immune system is under great pathogen-mediated selective pressure. A combination of divergent infectious disease pathogenesis across human populations, and the overrepresentation of “immune genes” in genomic regions with signatures of positive selection suggests that pathogens have significantly altered the human genome. However, important features of the human immune system can confound searches for and interpretations of signatures of pathogen-mediated evolution. Immune system redundancy, immune gene pleiotropy, host ability to acquire immunity and alter the immune repertoire of their offspring through “priming”, and host microbiome complicate evolutionary interpretations of host- pathogen interactions. The overall promiscuity and sensitivity of the ...


The Melanocortin Signaling Camp Axis Accelerates Repair And Reduces Mutagenesis Of Platinum-Induced Dna Damage, Stuart G. Jarrett, Katharine M. Carter, Brent J. Shelton, John A. D'Orazio 2017 University of Kentucky

The Melanocortin Signaling Camp Axis Accelerates Repair And Reduces Mutagenesis Of Platinum-Induced Dna Damage, Stuart G. Jarrett, Katharine M. Carter, Brent J. Shelton, John A. D'Orazio

Markey Cancer Center Faculty Publications

Using primary melanocytes and HEK293 cells, we found that cAMP signaling accelerates repair of bi- and mono-functional platinum-induced DNA damage. Elevating cAMP signaling either by the agonistic MC1R ligand melanocyte stimulating hormone (MSH) or by pharmacologic cAMP induction by forskolin enhanced clearance of intrastrand cisplatin-adducts in melanocytes or MC1R-transfected HEK293 cells. MC1R antagonists human beta-defensin 3 and agouti signaling protein blocked MSH- but not forskolin-mediated enhancement of platinum-induced DNA damage. cAMP-enhanced repair of cisplatin-induced DNA damage was dependent on PKA-mediated phosphorylation of ATR on S435 which promoted ATR’s interaction with the key NER factor xeroderma pigmentosum A (XPA) and ...


Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue 2017 The Graduate Center, City University of New York

Comparative Phylogeographic, Population Genomic, And Selection Inference With Development Of Hierarchical Co-Demographic Models, Alexander Xue

All Dissertations, Theses, and Capstone Projects

Comparing demographic histories across assemblages of populations, species, and sister pairs has been a focus in phylogeography since its inception. Initial approaches utilized organelle genetic data and involved qualitative comparisons of genetic patterns for evaluating hypotheses of shared evolutionary responses to past environmental changes. This endeavor has progressed with coalescent model-based statistical techniques and advances in next-generation sequencing, yet there remains a need for methods that can analyze aggregated genomic-scale data from non-model organisms within a unified framework that considers individual taxon uncertainty and variance. To this end, the aggregate site frequency spectrum (aSFS), an expansion of the site frequency ...


A Comparative Genome Analysis Of Cercospora Sojina With Other Members Of The Pathogen Genus Mycosphaerella On Different Plant Hosts, Fanchang Zeng, Xin Lian, Guirong Zhang, Xiaoman Yu, Carl A. Bradley, Ray Ming 2017 Shandong Agricultural University, China

A Comparative Genome Analysis Of Cercospora Sojina With Other Members Of The Pathogen Genus Mycosphaerella On Different Plant Hosts, Fanchang Zeng, Xin Lian, Guirong Zhang, Xiaoman Yu, Carl A. Bradley, Ray Ming

Plant Pathology Faculty Publications

Fungi are the causal agents of many of the world's most serious plant diseases causing disastrous consequences for large-scale agricultural production. Pathogenicity genomic basis is complex in fungi as multicellular eukaryotic pathogens. Here, we report the genome sequence of C. sojina, and comparative genome analysis with plant pathogen members of the genus Mycosphaerella (Zymoseptoria. tritici (synonyms M. graminicola), M. pini, M. populorum and M. fijiensis - pathogens of wheat, pine, poplar and banana, respectively). Synteny or collinearity was limited between genomes of major Mycosphaerella pathogens. Comparative analysis with these related pathogen genomes indicated distinct genome-wide repeat organization features. It suggests ...


Comprehensive Genomic Profiling In Routine Clinical Practice Leads To A Low Rate Of Benefit From Genotype-Directed Therapy, Talal Hilal, Mary Nakazawa, Jacob Hodskins, John L. Villano, Aju Mathew, Gaurav Goel, Lars M. Wagner, Susanne M. Arnold, Philip DeSimone, Lowell B. Anthony, Peter J. Hosein 2017 Mayo Clinic

Comprehensive Genomic Profiling In Routine Clinical Practice Leads To A Low Rate Of Benefit From Genotype-Directed Therapy, Talal Hilal, Mary Nakazawa, Jacob Hodskins, John L. Villano, Aju Mathew, Gaurav Goel, Lars M. Wagner, Susanne M. Arnold, Philip Desimone, Lowell B. Anthony, Peter J. Hosein

Markey Cancer Center Faculty Publications

Background: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.

Methods: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.

Results: A total of 125 pediatric ...


Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque 2017 The University of Western Ontario

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show ...


Comprehensive Genomic Sequencing Detects Important Genetic Differences Between Right-Sided And Left-Sided Colorectal Cancer, Yoshifumi Shimada, Stephen Lyle, Kazuaki Takabe, Toshifumi Wakai 2017 Niigata University

Comprehensive Genomic Sequencing Detects Important Genetic Differences Between Right-Sided And Left-Sided Colorectal Cancer, Yoshifumi Shimada, Stephen Lyle, Kazuaki Takabe, Toshifumi Wakai

Open Access Articles

Objectives: Anti-epidermal growth factor receptor (EGFR) therapy has been found to be more effective against left-sided colorectal cancer (LCRC) than right-sided colorectal cancer (RCRC). We hypothesized that RCRC is more likely to harbor genetic alterations associated with resistance to anti-EGFR therapy and tested this using comprehensive genomic sequencing.

Materials and methods: A total of 201 patients with either primary RCRC or LCRC were analyzed. We investigated tumors for genetic alterations using a 415-gene panel, which included alterations associated with resistance to anti-EGFR therapy: TK receptors (ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway (KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and ...


Transcriptional Regulation Of Cell-Type Specific Expression In The Arabidopsis Root, Keegan M. Leckie 2017 The University of Western Ontario

Transcriptional Regulation Of Cell-Type Specific Expression In The Arabidopsis Root, Keegan M. Leckie

Electronic Thesis and Dissertation Repository

Characterizing transcription factor interactions with their corresponding binding sites is crucial for understanding how gene expression is regulated by DNA sequence. A more comprehensive understanding of this process could have benefits in synthetic promoter design and creation of genetically modified organisms. Herein, the promoters of genes exhibiting cell-type specific expression within a single layer of the Arabidopsis root are analyzed to identify cis-regulatory motifs implicated in cell-type specific expression. De novo motif prediction identifies multiple motif candidates overly represented in the promoter sequences of co-expressed genes specific for epidermal, cortex, and endodermal expression. Several endodermal specific putative motifs are ...


Unravelling Organelle Genome Transcription Using Publicly Available Rna-Sequencing Data, Matheus Sanita Lima 2017 The University of Western Ontario

Unravelling Organelle Genome Transcription Using Publicly Available Rna-Sequencing Data, Matheus Sanita Lima

Electronic Thesis and Dissertation Repository

The study of organelles helped forge theories of genome evolution because of their unconventional genomes and gene expression regimes. The organelle genomics field (~35 years old) has seen the development of next generation sequencing (NGS) techniques and the consequent skyrocketing of genomic and transcriptomic data. However, these data are being underused in the studies of organelle genome transcription. My thesis investigates how NGS has affected the field of organelle genomics at both the DNA and RNA levels. First, I demonstrate that although organelle genomes are being sequenced as never before, they are un-characterized as they are published mostly as “organelle ...


Draft Nuclear Genome, Complete Chloroplast Genome, And Complete Mitochondrial Genome For The Biofuel/ Bioproduct Feedstock Species Scenedesmus Obliquus Strain Doe0152z, S. R. Starkenburg, Juergen Polle, B. Hovde, H. E. Daligault, K. W. Davenport, A. Huang, P. Neofotis, Zaid McKie-Krisberg 2017 Los Alamos National Laboratory

Draft Nuclear Genome, Complete Chloroplast Genome, And Complete Mitochondrial Genome For The Biofuel/ Bioproduct Feedstock Species Scenedesmus Obliquus Strain Doe0152z, S. R. Starkenburg, Juergen Polle, B. Hovde, H. E. Daligault, K. W. Davenport, A. Huang, P. Neofotis, Zaid Mckie-Krisberg

Publications and Research

The green alga Scenedesmus obliquus is an emerging platform species for the industrial production of biofuels. Here, we report the draft assembly and annotation for the nuclear, plastid, and mitochondrial genomes of S. obliquus strain DOE0152z.


The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription In The Swine Gut Microbiome, Timothy A. Johnson, Torey Looft, Andrew J. Severin, Darrell O. Bayles, Daniel J. Nasko, K. Eric Wommack, Adina Howe, Heather K. Allen 2017 United States Department of Agriculture

The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription In The Swine Gut Microbiome, Timothy A. Johnson, Torey Looft, Andrew J. Severin, Darrell O. Bayles, Daniel J. Nasko, K. Eric Wommack, Adina Howe, Heather K. Allen

Agricultural and Biosystems Engineering Publications

Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the ...


Heterogeneity And Intrinsic Variation In Spatial Genome Organization, Elizabeth Finn, Gianluca Pegoraro, Hugo B. Brandao, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom Misteli 2017 National Cancer Institute

Heterogeneity And Intrinsic Variation In Spatial Genome Organization, Elizabeth Finn, Gianluca Pegoraro, Hugo B. Brandao, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, Tom Misteli

University of Massachusetts Medical School Faculty Publications

The genome is hierarchically organized in 3D space and its architecture is altered in differentiation, development and disease. Some of the general principles that determine global 3D genome organization have been established. However, the extent and nature of cell-to-cell and cell-intrinsic variability in genome architecture are poorly characterized. Here, we systematically probe the heterogeneity in genome organization in human fibroblasts by combining high-resolution Hi-C datasets and high-throughput genome imaging. Optical mapping of several hundred genome interaction pairs at the single cell level demonstrates low steady-state frequencies of colocalization in the population and independent behavior of individual alleles in single nuclei ...


Detection, Diversity, And Evolution Of Fungal Nitric Oxide Reductases (P450nor), Steven Adam Higgins 2017 University of Tennessee, Knoxville

Detection, Diversity, And Evolution Of Fungal Nitric Oxide Reductases (P450nor), Steven Adam Higgins

Doctoral Dissertations

Nitrous oxide (N2O) is a gas responsible for significant ozone layer depletion and contributes to greenhouse effects in Earth’s atmosphere. N2O is primarily generated by denitrification, whereby nitrate (NO3-) or nitrite (NO2-) is converted to gaseous N2O or N2. Teragram quantities of N2O are emitted annually from agricultural soils treated with nitrogenous fertilizers due to the activity of soil microbiota. Although bacteria and fungi harbor genes permitting denitrification, fungi lack NosZ, an enzyme responsible for reducing N2O into inert N2 gas. Historically, scientists have linked fungi to ...


Assessment Of Genetic And Education Recovery Plan Objectives For The Bog Turtle (Glyptemys Muhlenbergii), Cassie Marie Dresser 2017 University of Tennessee, Knoxville

Assessment Of Genetic And Education Recovery Plan Objectives For The Bog Turtle (Glyptemys Muhlenbergii), Cassie Marie Dresser

Doctoral Dissertations

Unprecedented declines in biodiversity are threatening the natural world as we know it. Without human intervention, two thousand species listed under the US Endangered Species Act are likely to disappear. Fortunately, these species receive federal protection and increased research effort is needed to create and satisfy the objectives outlined in the mandated Species Recovery Plan. In this dissertation, I address three conservation objectives outlined in the Recovery Plan for North America’s smallest and rarest turtle, the Bog Turtle (Glyptemys muhlenbergii): (1) investigate the potential genetic differentiation in southern portions of the species’ range, (2) investigate the genetic impacts of ...


Vascular Endothelial Growth Factor A And Leptin Expression Associated With Ectopic Proliferation And Retinal Dysplasia In Zebrafish Optic Pathway Tumors, Laura E. Schultz, Staci L. Solin, Welsey A. Wierson, Janna M. Lovan, Judith Syrkin-Nikolau, Deborah E. Lincow, Andrew J. Severin, Donald S. Sakaguchi, Maura McGrail 2017 Iowa State University

Vascular Endothelial Growth Factor A And Leptin Expression Associated With Ectopic Proliferation And Retinal Dysplasia In Zebrafish Optic Pathway Tumors, Laura E. Schultz, Staci L. Solin, Welsey A. Wierson, Janna M. Lovan, Judith Syrkin-Nikolau, Deborah E. Lincow, Andrew J. Severin, Donald S. Sakaguchi, Maura Mcgrail

Genetics, Development and Cell Biology Publications

the central nervous system injury induces cellular reprogramming and progenitor proliferation, but the molecular mechanisms that limit regeneration and prevent tumorigenesis are not completely understood. We previously described a zebrafish optic pathway tumor model in which transgenic Tg(flk1:RFP)is18/+ adults develop nonmalignant retinal tumors. Key pathways driving injury-induced glial reprogramming and regeneration contributed to tumor formation. In this study, we examine a time course of proliferation and present new analyses of the Tg(flk1:RFP)is18/+ dysplastic retina and tumor transcriptomes. Retinal dysplasia was first detected in 3-month-old adults, but was not limited to a specific stem cell ...


Qpcr Detection Of Early Life History Stage Chrysaora Quinquecirrha (Sea Nettles) In Barnegat Bay, New Jersey, John J. Gaynor, Paul A.X. Bologna, Dena J. Restaino, Christie Barry 2017 Montclair State University

Qpcr Detection Of Early Life History Stage Chrysaora Quinquecirrha (Sea Nettles) In Barnegat Bay, New Jersey, John J. Gaynor, Paul A.X. Bologna, Dena J. Restaino, Christie Barry

Department of Biology Faculty Scholarship and Creative Works

The sea nettle Chrysaora quinquecirrha has become abundant in the Barnegat Bay estuary and frequently blooms in warm summer months. Various factors have been attributed to the increasing localized appearance of sea nettles and other jellyfish including eutrophication, overfishing, global warming, construction, and species introduction. Despite its abundance and frequent distribution within estuarine systems, very little work has been done to detect and quantify the early life history stages of this organism. Free-swimming larval stages of C. quinquecirrha can be detected and quantified using a quantitative polymerase chain reaction assay specific for the C. quinquecirrha 16S ribosomal (r)DNA locus ...


Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried 2017 University of Kentucky

Quaternary Interactions And Supercoiling Modulate The Cooperative Dna Binding Of Agt, Manana Melikishvili, Michael G. Fried

Center for Structural Biology Faculty Publications

Human O6-alkylguanine-DNA alkyltransferase (AGT) repairs mutagenic O6-alkylguanine and O4-alkylthymine adducts in single-stranded and duplex DNAs. The search for these lesions, through a vast excess of competing, unmodified genomic DNA, is a mechanistic challenge that may limit the repair rate in vivo. Here, we examine influences of DNA secondary structure and twist on protein–protein interactions in cooperative AGT complexes formed on lesion-free DNAs that model the unmodified parts of the genome. We used a new approach to resolve nearest neighbor (nn) and long-range (lr) components from the ensemble-average cooperativity, ωave. We found that ...


Clinical Application Of A Cancer Genomic Profiling Assay To Guide Precision Medicine Decisions, Cheryl Eifert, Angeliki Pantazi, Ruobai Sun, Jia Xu, Pablo Cingolani, Joerg Heyer, Meaghan Russell, Maria Lvova, Jennifer Ring, Julie Y. Tse, Stephen Lyle, Alexei Protopopov 2017 KEW, Inc.

Clinical Application Of A Cancer Genomic Profiling Assay To Guide Precision Medicine Decisions, Cheryl Eifert, Angeliki Pantazi, Ruobai Sun, Jia Xu, Pablo Cingolani, Joerg Heyer, Meaghan Russell, Maria Lvova, Jennifer Ring, Julie Y. Tse, Stephen Lyle, Alexei Protopopov

Open Access Articles

AIM: Develop and apply a comprehensive and accurate next-generation sequencing based assay to help clinicians to match oncology patients to therapies.

MATERIALS and METHODS: The performance of the CANCERPLEX(R) assay was assessed using DNA from well-characterized routine clinical formalin-fixed paraffin-embedded (FFPE) specimens and cell lines.

RESULTS: The maximum sensitivity of the assay is 99.5% and its accuracy is virtually 100% for detecting somatic alterations with an allele fraction of as low as 10%. Clinically actionable variants were identified in 93% of patients (930 of 1000) who underwent testing.

CONCLUSION: The test's capacity to determine all of the ...


Uploading Data To The Ncbi Sra Database, Raymond A. Enke 2017 enkera@jmu.edu

Uploading Data To The Ncbi Sra Database, Raymond A. Enke

Ray Enke Ph.D.

This in class exercise focuses on uploading FASTQ files sequencing data to the NCBI SRA database


An Approach To Identify Mycobacteriophage Diversity Prior To Dna Sequencing, Charles Gregory 2017 Western Kentucky University

An Approach To Identify Mycobacteriophage Diversity Prior To Dna Sequencing, Charles Gregory

Honors College Capstone Experience/Thesis Projects

Over 6,869 Mycobacteriophages have been isolated and purified. Of these, 1,367 genomes have been sequenced at the DNA level and more are added each year through the SEA-PHAGES program. Sequenced mycobacteriophages are grouped into clusters based on a 50% or greater nucleotide identity. The number and breadth of these clusters represents the diversity present in the environment. Each year, as new phages are discovered by students in the SEA-PHAGES program, the question arises, “Which isolates should we sequence?” In order to sequence phages that represent the greatest possible diversity, and thus broaden under-represented clusters and identify new singletons ...


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