Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, 2018 James Madison University
Evolution Of Bordetella Pertussis Genome May Play A Role In The Increased Rate Of Whooping Cough Cases In The United States, Kevin Loftus
Senior Honors Projects, 2010-2019
Bordetella pertussis is the bacterium responsible for pertussis, a disease commonly referred to as whooping cough. Recently, pertussis has made a resurgence in the U.S. despite high-vaccination coverage. Possible causes of the increased number of pertussis cases include genetic evolution of B. pertussis, increased awareness of the disease, better laboratory diagnostics, and the switch from a whole-cellular (wP) vaccine to an acellular vaccine (aP) in the 1990s. Fortunately, just as B. pertussis is evolving, so is the arsenal of technologies used to understand and combat this pathogenic bacterium. Whole genome sequencing is one technology that helps researchers better understand ...
Thalamocortical Processing Of Temporal Cues In Sounds, 2018 University of Connecticut
Thalamocortical Processing Of Temporal Cues In Sounds, Kasey Smith
Honors Scholar Theses
The ability of the brain to extract meaningful information from complex sounds is what allows mammals to understand species-specific communication as well as important environmental cues such as the sound of water or of potential predators or prey. The auditory cortex of humans and other mammals contains multiple cortical regions that unique sensitivities to both spectral and temporal sound cues. This discourse will explore three main factors proposed to determine these distinct processing capabilities in regard to temporal sound cues; the distribution of glutamate transporters in the thalamus, the architecture of afferent pathways between the thalamus and auditory cortex, and ...
Genome-Wide Association Study Of Offspring Birth Weight In 86 577 Women Identifies Five Novel Loci And Highlights Maternal Genetic Effects That Are Independent Of Fetal Genetics, 2018 University of Exeter
Genome-Wide Association Study Of Offspring Birth Weight In 86 577 Women Identifies Five Novel Loci And Highlights Maternal Genetic Effects That Are Independent Of Fetal Genetics, Robin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C Richmond, Lavinia Paternoster, Jonathan P. Bradfield, Eskil Kreiner-Møller, Ville Huikari, Sarah Metrustry, Kathryn L. Lunetta, Jodie N. Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J. Barton, Ana Espinosa, Julie A. Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J. Berry, Luigi Bouchard, Shikta Das, Early Growth Genetics (Egg) Consortium, Hakon Hakonarson, Jani Heikkinen, Øyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M Inskip, Samuel E Jones, Manolis Kogevinas, Penelope A Lind, Letizia Marullo, Sarah E Medland, Anna Murray, Jeffrey C Murray, Pål R Njølstad, Ellen A Nohr, Christoph Reichetzeder, Susan M Ring, Katherine S Ruth, Loreto Santa-Marina, Denise M Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A Tuke, Marc Vaudel, Michael N Weedon, Gonneke Willemsen, Andrew R Wood, Hanieh Yaghootkar, Louis J Muglia, Meike Bartels, Caroline L Relton, Craig E Pennell, Leda Chatzi, Xavier Estivill, John W Holloway, Dorret I Boomsma, Grant W Montgomery, Joanne M Murabito, Tim D Spector, Christine Power, Marjo-Ritta Järvelin, Hans Bisgaard, Struan F.A. Grant, Thorkild I.A. Sørensen, Vincent W Jaddoe, Bo Jacobsson, Mads Melbye, Mark I Mccarthy, Andrew T Hattersley, M Geoffery Hayes, Timothy M Frayling, Marie-France Hivert, Janine F Felix, Elina Hyppönen, William L Lowe Jr., David M Evans, Debbie A Lawlor, Bjarke Feenstra, Rachel M Freathy
Stead Family Department of Pediatrics Publications
Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B ...
A Plasma Telomeric Cell-Free Dna Level In Unaffected Women With Brca1 Or/And Brca2 Mutations: A Pilot Study, Shatovisha Dey, Natascia Marino, Kanokwan Bishop, Paige N. Dahlgren, Aditi Shendre, Anna Maria Storniolo, Chunyan He, Hiromi Tanaka
Internal Medicine Faculty Publications
Plasma cell-free DNA (cfDNA) is a small DNA fragment circulating in the bloodstream originating from both non-tumor- and tumor-derived cells. A previous study showed that a plasma telomeric cfDNA level decreases in sporadic breast cancer patients compared to controls. Tumor suppressor gene products including BRCA1 and BRCA2 (BRCA1&2) play an important role in telomere maintenance. In this study, we hypothesized that the plasma telomeric cfDNA level is associated with the mutation status of BRCA1&2 genes. To test this hypothesis, we performed plasma telomeric cfDNA quantitative PCR (qPCR)-based assays to compare 28 women carriers of the BRCA1&2 ...
Centenarian, 2018 Iowa State University
Centenarian, Peter Martin, Yousun Baek
Human Development and Family Studies Publications
A centenarian is an individual who has survived to the age of 100, approximately 20 years longer than the average life expectancy. The number of centenarians in the United States has increased and will continue to increase. According to census data, 53,364 centenarians were alive in the United States in 2010, an increase of 65.8% over the last 30 years. More supercentenarians (those who have attained the age of 110 years or older) are also found around the world. Jeanne Louise Calment of France is known to have attained the oldest age ever, 122 years and 164 days ...
Novel Caries Loci In Children And Adults Implicated By Genome-Wide Analysis Of Families, 2018 University of Pittsburgh
Novel Caries Loci In Children And Adults Implicated By Genome-Wide Analysis Of Families, Manika Govil, Nandita Mukhopadhyay, Daniel E. Weeks, Eleanor Feingold, John R. Shaffer, Steven M. Levy, Alexandre R. Vieira, Rebecca L. Slayton, Daniel W. Mcneil, Robert J. Weyant, Richard J. Crout, Mary L. Marazita
Faculty & Staff Scholarship
Background: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited.
Methods: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and ...
Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, 2017 University of Denver
Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elyssia Poggi Davis, Judith E. Carroll, Laura M. Glynn
Psychology Faculty Articles and Research
Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.
Methods: TL was measured ...
Mechanism Of Transcription Anti-Termination In Human Mitochondria., 2017 Max Planck Institute for Biophysical Chemistry
Mechanism Of Transcription Anti-Termination In Human Mitochondria., Hauke S Hillen, Andrey V Parshin, Karen Agaronyan, Yaroslav I Morozov, James J Graber, Aleksandar Chernev, Kathrin Schwinghammer, Henning Urlaub, Michael Anikin, Patrick Cramer, Dmitry Temiakov
School of Osteopathic Medicine Faculty Scholarship
In human mitochondria, transcription termination events at a G-quadruplex region near the replication origin are thought to drive replication of mtDNA by generation of an RNA primer. This process is suppressed by a key regulator of mtDNA-the transcription factor TEFM. We determined the structure of an anti-termination complex in which TEFM is bound to transcribing mtRNAP. The structure reveals interactions of the dimeric pseudonuclease core of TEFM with mobile structural elements in mtRNAP and the nucleic acid components of the elongation complex (EC). Binding of TEFM to the DNA forms a downstream "sliding clamp," providing high processivity to the EC ...
Endonucleolytic Cleavage In The Expansion Segment 7 Of 25s Rrna Is An Early Marker Of Low-Level Oxidative Stress In Yeast, Daniel Shedlovskiy, Jessica A Zinskie, Ethan Gardner, Dimitri G Pestov, Natalia Shcherbik
School of Osteopathic Medicine Faculty Scholarship
The ability to detect and respond to oxidative stress is crucial to the survival of living organisms. In cells, sensing of increased levels of reactive oxygen species (ROS) activates many defensive mechanisms that limit or repair damage to cell components. The ROS-signaling responses necessary for cell survival under oxidative stress conditions remain incompletely understood, especially for the translational machinery. Here, we found that drug treatments or a genetic deficiency in the thioredoxin system that increase levels of endogenous hydrogen peroxide in the yeast Saccharomyces cerevisiae promote site-specific endonucleolytic cleavage in 25S ribosomal RNA (rRNA) adjacent to the c loop of ...
Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, 2017 University of Pennsylvania
Genome-Wide Top2a Dna Cleavage Is Biased Toward Translocated And Highly Transcribed Loci, Xiang Yu, James W. Davenport, Karen A. Urtishak, Marie L. Carillo, Sager J. Gosai, Christos P. Kolaris, Jo Ann W. Byl, Eric F. Rappaport, Neil Osheroff, Brian D. Gregory, Carolyn A. Felix
Departmental Papers (Biology)
Type II topoisomerases orchestrate proper DNA topology, and they are the targets of anti-cancer drugs that cause treatment-related leukemias with balanced translocations. Here, we develop a high-throughput sequencing technology to define TOP2 cleavage sites at single-base precision, and use the technology to characterize TOP2A cleavage genome-wide in the human K562 leukemia cell line. We find that TOP2A cleavage has functionally conserved local sequence preferences, occurs in cleavage cluster regions (CCRs), and is enriched in introns and lincRNA loci. TOP2A CCRs are biased toward the distal regions of gene bodies, and TOP2 poisons cause a proximal shift in their distribution. We ...
Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough
Background: Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal ...
Mitochondrial Dna Heteroplasmy In Cardiac Tissue From Individuals With And Without Coronary Artery Disease, 2017 Harrisburg University of Science and Technology
Mitochondrial Dna Heteroplasmy In Cardiac Tissue From Individuals With And Without Coronary Artery Disease, Erik Hefti, Javier G. Blanco
Harrisburg University Faculty Works
The cellular environment associated with coronary artery disease (CAD) can lead to mitochondrial DNA (mtDNA) damage. Mitochondrial variants in some copies of mtDNA (heteroplasmy) and mtDNA content are potential genetic biomarkers for CAD-associated disease states. Massively parallel sequencing and qRT-PCR techniques were used to measure heteroplasmic variants and mtDNA content in heart samples from donors with (n = 8) and without (n = 7) documented CAD. Both groups showed increased numbers of heteroplasmic mtDNA variants in the control region (CR) (p < .0010, ANOVA). The donors with CAD displayed a 41.07% increase in heteroplasmic mtDNA variant number in the CR (p = .043), an 87.50% increase in the number of heteroplasmic mtDNA deletions (p = .12), and a 48.76% increase in ... .0010,>
Evidence Of Strain Structure In Plasmodium Falciparum Var Gene Repertoires In Children From Gabon, West Africa, 2017 New York Medical College
Evidence Of Strain Structure In Plasmodium Falciparum Var Gene Repertoires In Children From Gabon, West Africa, K Day, Y Artzy-Randrup, K Tiedje, V Rougeron, Donald S. Chen, T Rask, M Rorick, F Migot-Nabias, P Deloron, A Luty, M Pascual
NYMC Faculty Publications
Existing theory on competition for hosts between pathogen strains has proposed that immune selection can lead to the maintenance of strain structure consisting of discrete, weakly overlapping antigenic repertoires. This prediction of strain theory has conceptual overlap with fundamental ideas in ecology on niche partitioning and limiting similarity between coexisting species in an ecosystem, which oppose the hypothesis of neutral coexistence. For Plasmodium falciparum, strain theory has been specifically proposed in relation to the major surface antigen of the blood stage, known as PfEMP1 and encoded by the multicopy multigene family known as the var genes. Deep sampling of the ...
Activity Of Distinct Growth Factor Receptor Network Components In Breast Tumors Uncovers Two Biologically Relevant Subtypes, Moom Roosan, Shelley M. Macneil, David F. Jenkins, Gajendra Shrestha, Sydney R. Wyatt, Jasmine A. Mcquerry, Stephen R. Piccolo, Laura M. Heiser, Joe W. Gray, W. Evan Johnson, Andrea H. Bild
Pharmacy Faculty Articles and Research
The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns.
Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD). The pathway analysis toolkit Adaptive Signature Selection ...
Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., 2017 Children's Mercy Hospital
Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis
Manuscripts, Articles, Book Chapters and Other Papers
Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort ...
Novel Genetic Variants Associated With Child Refractory Esophageal Stricture With Food Allergy By Exome Sequencing., 2017 Children's Mercy Hospital
Novel Genetic Variants Associated With Child Refractory Esophageal Stricture With Food Allergy By Exome Sequencing., Min Yang, Min Xiong, Huan Chen, Lanlan Geng, Peiyu Chen, Jing Xie, Shui Qing Ye, Ding-You Li, Sitang Gong
Manuscripts, Articles, Book Chapters and Other Papers
BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets.
METHODS: To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy.
RESULTS: A total of 91,024 variants were identified. By filtering out 'normal variants' against those of the 1000 Genomes Project, we identified 12,741 remaining variants which are potentially associated with ...
Synthesis And Anti-Hiv Activities Of Unsymmetrical Long Chain Dicarboxylate Esters Of Dinucleosides Reverse Transcriptase Inhibitors, Hitesh K. Agarwal, Bhupender S. Chhikara, Gustavo F. Doncel, Keykavous Parang
Pharmacy Faculty Articles and Research
A series of 11 unsymmetrical dinucleoside dicarboxylate conjugates of nucleoside reverse transcriptase inhibitors were synthesized. Three dicarboxylic acids, succinic acid, suberic acid and 1,14-tetradecandioc acid, were diesterified with either 3'-azido- 2',3'-dideoxythymidine (AZT), 3'-fluoro-2',3'-dideoxythymidine (FLT), 2',3'-dideoxy-3'-thiacytidine (3TC) or 5-fluoro-2',3'-dideoxy-3'- thiacytidine (FTC). The anti-HIV activity of synthesized compounds was evaluated against HIV-1 X4 (IIIB) and R5 (BaL) viral strains in single-round infection assays. Results indicated that the tetradecandioate esters of nucleosides were more active against HIV than the corresponding parent nucleosides and nucleoside conjugates. The tetradecandioate conjugate of FLT and ...
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, 2017 Western University
P33. Design And Evaluation Of An Escherichia Coli Biomarker For Indication Of Ph, Kevin X. Zhou, Luana Langlois, Ashmita Singh, John Prince
Western Research Forum
Measuring pH is one of the most commonly used techniques in both the laboratory as well as the field due to its importance in a multitude of biochemical processes. Traditional methods of measuring pH may be highly developed in accuracy and precision but often involve disruption of the environment. Biological markers offer an alternative that allows for long-term pH monitoring. This innovative approach allows for vast applications such as in the manufacturing, food processing and research industries. Under moderate acidic conditions, the asr (acid shock RNA) gene is highly inducible and has been demonstrated to be crucial for growth at ...
The Dynamic Nature Of Chromatin, 2017 University of Kentucky
The Dynamic Nature Of Chromatin, Caitlyn M. Riedmann
Theses and Dissertations--Molecular and Cellular Biochemistry
Eukaryotic organisms contain their entire genome in the nucleus of their cells. In order to fit within the nucleus, genomic DNA wraps into nucleosomes, the basic, repeating unit of chromatin. Nucleosomes wrap around each other to form higher order chromatin structures. Here we study many factors that affect, or are effected by, chromatin structure including: (1) how low-dose inorganic arsenic (iAs) changes chromatin structures and their relation to global transcription and splicing patterns, and (2) how chromatin architectural proteins (CAPs) bind to and change nucleosome dynamics and DNA target site accessibility.
Despite iAs’s non-mutagenic nature, chronic exposure to low ...
Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, 2017 Marshall University
Employing The Enzyme Cofactor Function Of Ascorbic Acid To Affect Oncogenic Pathways In Human Melanoma: Modulating Hypoxia Inducible Factor-1Α And Dna Demethylation To Reduce Malignant Potential, Adam Patrick Fischer
Theses, Dissertations and Capstones
Dioxygenase enzymes such as the HIF hydroxylases (PHD1-3, FIH) and the Ten-eleven translocation (TET1-3) enzymes regulate the activity of the hypoxia inducible factor-1a (HIF1a) transcription factor and the DNA methylation status of cells, respectively. Aberrant accumulation and activation of HIF-1a can allow malignant cells to acquire attributes that promote progression, chemotherapy resistance, and survival, while aberrant hypermethylation of gene promoters can silence the expression of tumor suppressor genes essential to preventing tumorigenesis. Inadequate levels of intracellular ascorbic acid (AA), a necessary cofactor for optimal dioxygenase enzyme function, could potentiate these tumorigenic conditions. In fact, plasma levels of ...