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 ...
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 ...
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 ...
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, 2017 University of Colorado Boulder
A Study Of Subthreshold Hallucinatory Experiences And Their Relationship To Genetic Liability For Schizophrenia, Hannah Young
Undergraduate Honors Theses
One of the hallmarks of schizophrenia is the presence of psychosis. However, subthreshold psychotic symptoms characterized by attenuated delusions and hallucinations also occur in healthy individuals from the general population. A body of evidence suggests that this phenomenon represents a continuum of schizophrenia, with severe and attenuated symptoms sharing a common genetic etiology. Hallucinations are one subthreshold psychotic symptom in which a clear continuum has been observed. The aim of this study is to assess if subthreshold hallucinatory experiences and schizophrenia share genetic liability.
3,028 participants were administered the Launay-Slade Hallucination Scale (LSHS), which measures a predisposition ...
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 ...
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, 2016 University of New England
A Tale Of Two Species: Evolvability, Genomic Context, And Pathogen Forecasting, Meghan May
Biomedical Sciences Faculty Presentations
Dr. Meghan May gives an overview presentation of her research on evolution of virulence and pathogen prediction. The focus of the presentation is a group of organisms called mycoplasmas, and covered subjects include: Mycoplasma synoviae, Mycoplasma gallisepticum, genomic context, predictive modeling, sequence evolution, and genome reduction.
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, 2016 Wayne State Center for Molecular Medicine and Genetics, Wayne State University
High-Throughput Allele-Specific Expression Across 250 Environmental Conditions, Gregory A. Moyerbrailean, Allison L. Richards, Daniel Kurtz, Cynthia A. Kalita, Gordon O. Davis, Chris T. Harvey, Adnan Alazizi, Donovan Watza, Yoram Sorokin, Nancy J. Hauff, Xiang Zhou, Xiaoquan Wen, Roger Pique-Regi, Francesca Luca
Center for Molecular Medicine and Genetics
Gene-by-environment (GxE) interactions determine common disease risk factors and biomedically relevant complex traits. However, quantifying how the environment modulates genetic effects on human quantitative phenotypes presents unique challenges. Environmental covariates are complex and difficult to measure and control at the organismal level, as found in GWAS and epidemiological studies. An alternative approach focuses on the cellular environment using in vitro treatments as a proxy for the organismal environment. These cellular environments simplify the organism-level environmental exposures to provide a tractable influence on subcellular phenotypes, such as gene expression. Expression quantitative trait loci (eQTL) mapping studies identified GxE interactions in response ...
Comparing Performance Of Non-Tree-Based And Tree-Based Association Mapping Methods, 2016 University of Kentucky
Comparing Performance Of Non-Tree-Based And Tree-Based Association Mapping Methods, Katherine L. Thompson, David W. Fardo
Statistics Faculty Publications
A central goal in the biomedical and biological sciences is to link variation in quantitative traits to locations along the genome (single nucleotide polymorphisms). Sequencing technology has rapidly advanced in recent decades, along with the statistical methodology to analyze genetic data. Two classes of association mapping methods exist: those that account for the evolutionary relatedness among individuals, and those that ignore the evolutionary relationships among individuals. While the former methods more fully use implicit information in the data, the latter methods are more flexible in the types of data they can handle. This study presents a comparison of the 2 ...
The Long Non-Coding Rna Malat1 Regulates Inflammatory Cytokine Production In Chronic Diabetic Complications, 2016 The University of Western Ontario
The Long Non-Coding Rna Malat1 Regulates Inflammatory Cytokine Production In Chronic Diabetic Complications, Andrew D. Gordon
Electronic Thesis and Dissertation Repository
We examined the role of MALAT1, a highly conserved nuclear lncRNA, in chronic diabetic complications affecting the heart and kidneys, specifically with respect to inflammatory cytokine production. Endothelial cells, exposed to various glucose levels, and MALAT1 knockout mice and controls, with or without streptozotocin-induced diabetes were examined. Endothelial cells cultured with high glucose, and renal and cardiac tissue from diabetic mice showed increased inflammatory cytokine (eg. IL-6, IL1β, TNFα) production along with transient MALAT1 upregulation. This was confirmed by both transcript and protein analyses, and such changes were prevented in the MALAT1 knockout diabetic animals. In the malat1 knockout animals ...
Cellular Pathways In The Repair And Tolerance Of Formaldehyde-Induced Dna Damage, 2016 Oregon Health & Science University
Cellular Pathways In The Repair And Tolerance Of Formaldehyde-Induced Dna Damage, Eleonora Juarez
No abstract provided.
Analyzing Mutations Of Spt7 Protein That Disrupt Interaction With Sf3b Subunits, 2016 Purdue University
Analyzing Mutations Of Spt7 Protein That Disrupt Interaction With Sf3b Subunits, Arryn T. Harris, Peyton J. Spreacker, Rachel Stegeman, Vikki M. Weake, Edwin C. Acosta
The Summer Undergraduate Research Fellowship (SURF) Symposium
Proper transcription, the process of converting DNA to RNA, is crucial for the health and viability of an organism. This process is regulated by many proteins, such as co-transcriptional activators; one being the protein complex known as Spt-Ada-Gcn5-acetyltransferase, or SAGA. While much is known about the roles of SAGA in cell processes, how SAGA’s subunits promote functionality is still unknown. The focus of this study is to analyze the purpose of SAGA’s SF3B subunits. These subunits are also found in the spliceosome, the compound responsible for generating mature RNA. SAGA has no known functions relating to this process ...
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, 2016 Northwestern Polytechnical University
Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han
Pharmacy Faculty Articles and Research
The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no ...
Comparative Genomic Mapping Of Uncharacterized Canine Retinal Ests To Identify Novel Candidate Genes For Hereditary Retinal Disorders, Barbara Zangerl, Jennifer Johnson, Jarek Pillardy, Qi Sun, Catherine André, Francis Galibert, Gregory Acland, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: To identify the genomic location of previously uncharacterized canine retina-expressed expressed sequence tags (ESTs), and thus identify potential candidate genes for heritable retinal disorders. Methods: A set of over 500 retinal canine ESTs were mapped onto the canine genome using the RHDF5000–2 radiation hybrid (RH) panel, and the resulting map positions were compared to their respective localization in the CanFam2 assembly of the canine genome sequence. Results: Unique map positions could be assigned for 99% of the mapped clones, of which only 29% showed significant homology to known RefSeq sequences. A comparison between RH map and sequence assembly ...
Cloning And Characterization Of Canine Pax6 And Evaluation As A Candidate Gene In A Canine Model Of Aniridia, 2016 University of Pennsylvania
Cloning And Characterization Of Canine Pax6 And Evaluation As A Candidate Gene In A Canine Model Of Aniridia, Linda Hunter, Duska Sidjanin, Manuel Villagrasa Hijar, Jennifer Johnson, Ewen Kirkness, Gregory Acland, Gustavo Aguirre
Gustavo D. Aguirre, VMD, PhD
Purpose: Mutations in PAX6 cause human aniridia. The small eye (sey) mouse represents an animal model for aniridia. However, no large animal model currently exists. We cloned and characterized canine PAX6, and evaluated PAX6 for causal associations with inherited aniridia in dogs. Methods: Canine PAX6 was cloned from a canine retinal cDNA library using primers designed from human and mouse PAX6 consensus sequences. An RH3000 radiation hybrid panel was used to localize PAX6 within the canine genome. Genomic DNA was extracted from whole blood of dogs with inherited aniridia, and association testing was performed using markers on CFA18. Fourteen PAX6 ...
Il-15 Mediates Mitochondrial Activity Through A Ppar𝛿-Dependent-Ppar𝛼-Independent Mechanism In Skeletal Muscle Cells, Shantaé M. Thornton, James E. Krolopp, Marcia J. Abbott
Health Sciences and Kinesiology Faculty Articles
Molecular mediators of metabolic processes, to increase energy expenditure, have become a focus for therapies of obesity. The discovery of cytokines secreted from the skeletal muscle (SKM), termed “myokines,” has garnered attention due to their positive effects on metabolic processes. Interleukin-15 (IL-15) is a myokine that has numerous positive metabolic effects and is linked to the PPAR family of mitochondrial regulators. Here, we aimed to determine the importance of PPAR𝛼 and/or PPAR𝛿 as targets of IL-15 signaling. C2C12 SKM cells were differentiated for 6 days and treated every other day with IL-15 (100 ng/mL), a PPAR𝛼 inhibitor (GW-6471 ...
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, 2016 University of Kentucky
Molecular Genetics Of Ms4a6a And Alzheimer's Disease, Ryan Harpole
Lewis Honors College Capstone Collection
Increased Alzheimer’s disease (AD) risk has previously been associated with a SNP called rs610932 near the gene MS4A6A. The goal of this experiment was to quantify the expression of two MS4A6A isoforms in the brains of AD and non-AD subjects, particularly as a function of rs610932 genotype. According to an article titled “Alzheimer’s Disease Susceptibility Variants in the MS4A6A Gene are Associated with Altered Levels of MS4A6A Expression in Blood”, MS4A6A has four different isoforms that have been reported to be differentially expressed in the blood of AD subjects compared to non-AD subjects (Petroula et al., 2014). After ...
An Overview Of Leber’S Hereditary Optic Neuropathy, 2015 Liberty University
An Overview Of Leber’S Hereditary Optic Neuropathy, Matthew R. Dalton
Typically affecting males ranging from 20 to 24 years of age, Leber’s Hereditary Optic Neuropathy (LHON) is a disorder that is characterized by an acute loss of central vision. Although a heritable disease, LHON does not follow the patterns of classical Mendelian genetics. In fact, one of the most striking characteristics of LHON is that the disease is virtually always inherited maternally. Unlike most genetic disorders that result from a mutation in genomic DNA, LHON is caused by a mutation in the genetic information of mitochondria (mtDNA). Currently there is no treatment for LHON. Despite this, pharmaceutical interventions and ...
Development Of A Comprehensive Massively Parallel Sequencing Panel Of Single Nucleotide Polymorphism And Short Tandem Repeat Markers For Human Identification, 2015 University of North Texas Health Science Center at Fort Worth
Development Of A Comprehensive Massively Parallel Sequencing Panel Of Single Nucleotide Polymorphism And Short Tandem Repeat Markers For Human Identification, David H. Warshauer
Theses and Dissertations
Massively parallel sequencing (MPS) technologies allow for the detection of an unparalleled amount of genetic information with unprecedented speed and relative ease. These qualities make the technology desirable for generating DNA profiles that may be uploaded into forensic offender, arrestee, and family reference database files. This doctoral dissertation research was conducted under the hypothesis that MPS, with its exquisitely high throughput, can provide a system whereby reference samples can be typed for a large battery of markers, providing more discrimination power for forensic DNA typing and offering increased opportunities to develop investigative leads. The design and implementation of large marker ...
Selection Of An Ancestry-Informative Marker (Aim) Panel Of Indels, 2015 University of North Texas Health Science Center at Fort Worth
Selection Of An Ancestry-Informative Marker (Aim) Panel Of Indels, Lindsey M. Thompson B.S.
Theses and Dissertations
Short Tandem Repeat (STR) loci are commonly used for forensic identification purposes. Most commercially available STR kits yield amplified fragments with lengths between 100 and 600 base pairs (bp). However, the genomic DNA of forensic samples can be highly degraded, yielding incomplete STR profiles. Small insertion/deletion polymorphisms (INDELs) in the intergenic regions of the genome, are viable options for typing degraded samples. Furthermore, when there are no suspects for comparison, ancestry-informative markers (AIMs) are useful for developing investigative leads. This project tested the hypothesis that using publicly available genome data, a panel of AIM-INDELs can be selected for the ...