Life Sciences Commons^™

Structural Basis For Dna Proofreading, Gina Buchel, Ashok Nayak, Karl Herbine, Azadeh Sarfallah, Viktoriia Sokolova, Angelica Zamudio-Ochoa, Dmitry Temiakov

Department of Biochemistry and Molecular Biology Faculty Papers

DNA polymerase (DNAP) can correct errors in DNA during replication by proofreading, a process critical for cell viability. However, the mechanism by which an erroneously incorporated base translocates from the polymerase to the exonuclease site and the corrected DNA terminus returns has remained elusive. Here, we present an ensemble of nine high-resolution structures representing human mitochondrial DNA polymerase Gamma, Polγ, captured during consecutive proofreading steps. The structures reveal key events, including mismatched base recognition, its dissociation from the polymerase site, forward translocation of DNAP, alterations in DNA trajectory, repositioning and refolding of elements for primer separation, DNAP backtracking, and displacement …

Dna Barcoding Indicates Multiple Invasions Of The Freshwater Snail Melanoides Tuberculata Sensu Lato In Florida, Lori Tolley-Jordan, Michael A. Chadwick, Jimmy K. Triplett

Research, Publications & Creative Work

Melanoides tuberculata sensu lato (Thiaridae) are polymorphic female-clonal snails of Asian and African origins that have invaded freshwaters worldwide, including those in Florida. Although the snails have been documented in Florida for at least 70 years, no studies have investigated whether the observed distribution is due to a single introduction or multiple independent invasions. Here, cytochrome oxidase I was used to measure genetic diversity within and among sites in Florida and compare genetic diversity between Florida and other regions of the world. We also examined the relationship between shell morphology and haplotype diversity to determine if shell morphs can serve …

Association Between Whole Blood-Derived Mitochondrial Dna Copy Number, Low-Density Lipoprotein Cholesterol, And Cardiovascular Disease Risk, Xue Liu, Xianbang Sun, Yuankai Zhang, Wenqing Jiang, Meng Lai, Kerri L Wiggins, Laura M Raffield, Lawrence F Bielak, Wei Zhao, Achilleas Pitsillides, Jeffrey Haessler, Yinan Zheng, Thomas W Blackwell, Jie Yao, Xiuqing Guo, Yong Qian, Bharat Thyagarajan, Nathan Pankratz, Stephen S Rich, Kent D Taylor, Patricia A Peyser, Susan R Heckbert, Sudha Seshadri, Eric Boerwinkle, Megan L Grove, Nicholas B Larson, Jennifer A Smith, Ramachandran S Vasan, Annette L Fitzpatrick, Myriam Fornage, Jun Ding, April P Carson, Goncalo Abecasis, Josée Dupuis, Alexander Reiner, Charles Kooperberg, Lifang Hou, Bruce M Psaty, James G Wilson, Daniel Levy, Jerome I Rotter, Joshua C Bis, Claudia L Satizabal, Dan E Arking, Chunyu Liu

Journal Articles

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross-sectional and prospective association analyses of blood-derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole-genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia).

Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield

PANDION: The Osprey Journal of Research and Ideas

Origins of life research, also known as pre-biotic chemistry or astrobiology, aims to unravel the mystery of the first cell’s origin on Earth. This interdisciplinary field encompasses biology, chemistry, and physics, with the primary goal of understanding the conditions necessary for life to emerge from abiotic environments. The RNA world hypothesis suggests that early life initially used RNA instead of DNA to store genomic information and for enzymatic functions. Protocells, membrane-bound entities with metabolic processes and self-replication capabilities, likely preceded the emergence of true cells. The challenges associated with RNA world is currently an active field of research. Advancements in …

Animal Board Invited Review: Practical Applications Of Genomic Information In Livestock, D. P. Berry, Matthew L. Spangler

Department of Animal Science: Faculty Publications

Access to high-dimensional genomic information in many livestock species is accelerating. This has been greatly aided not only by continual reductions in genotyping costs but also an expansion in the services available that leverage genomic information to create a greater return-on-investment. Genomic information on individual animals has many uses including (1) parentage verification and discovery, (2) traceability, (3) karyotyping, (4) sex determination, (5) reporting and monitoring of mutations conferring major effects or congenital defects, (6) better estimating inbreeding of individuals and coancestry among individuals, (7) mating advice, (8) determining breed composition, (9) enabling precision management, and (10) genomic evaluations; genomic …

Saturating Growth Rate Against Phosphorus Concentration Explained By Macromolecular Allocation, Gabrielle Armin, Jongsun Kim, Keisuke Inomura

School of Earth, Environmental, and Marine Sciences Faculty Publications and Presentations

The saturating relationship between phytoplankton growth rate and environmental nutrient concentration has been widely observed, yet the mechanisms behind the relationship remain elusive. Here, we use a mechanistic model of phytoplankton and show that the saturating relationship between growth rate and phosphorous concentration can be interpreted by intracellular macromolecular allocation. At low nutrient levels, the diffusive nutrient transport linearly increases with the phosphorous concentration, while the internal phosphorous requirement increases with the growth rate, leading to a non-linear increase in the growth rate with phosphorous. This increased phosphorous requirement is due to the increased allocation to biosynthetic and photosynthetic molecules. …

Effects Of Group Ii Metal Binding On The Stability Of Dna I-Motif Structures, Charlotte Powers

Honors Theses

B-form DNA can adopt alternative structures while in superhelical duress. Alternative DNA structures are favored when there is an asymmetric distribution on complementary DNA strands. Cytosine rich strands may utilize cytosine-cytosine base pairing to form a four-stranded structure known as the i-motif (iM). The stability of iMs is affected by several factors such as DNA sequence, temperature, pH, ionic strength of the solution, and crowded conditions. While the effects of temperature, pH, and crowding conditions on iM stability have been well documented, the effects of ion presence in a solution has been less studied. Hence, those studies are the basis …

Exploring The Interaction Of Minor-Groove-Binder Netropsin With Dna Using Optical Tweezers, Irbazhusain Shaikh

Honors Program Theses and Projects

Netropsin is an antibiotic that binds in the minor grooves of DNA, which also exhibits anticancer properties. There have been many previous studies that explored the binding of this drug to DNA using traditional methods where an ensemble averaging is used. In this study we explore the interaction of Netropsin with DNA at a single molecule level using dual beam optical tweezers. We trapped and stretched a single DNA molecule using optical tweezers to measure the force experienced by the DNA as a function of extension in the absence and presence of various concentrations of Netropsin. Our results show the …

Association Of Mitochondrial Dna Copy Number With Brain Mri Markers And Cognitive Function: A Meta-Analysis Of Community-Based Cohorts, Yuankai Zhang, Xue Liu, Kerri L Wiggins, Nuzulul Kurniansyah, Xiuqing Guo, Amanda L Rodrigue, Wei Zhao, Lisa R Yanek, Scott M Ratliff, Achilleas Pitsillides, Juan Sebastian Aguirre Patiño, Tamar Sofer, Dan E Arking, Thomas R Austin, Alexa S Beiser, John Blangero, Eric Boerwinkle, Jan Bressler, Joanne E Curran, Lifang Hou, Timothy M Hughes, Sharon L R Kardia, Lenore J Launer, Daniel Levy, Thomas H Mosley, Ilya M Nasrallah, Stephen S Rich, Jerome I Rotter, Sudha Seshadri, Wassim Tarraf, Kevin A González, Vasan Ramachandran, Kristine Yaffe, Paul A Nyquist, Bruce M Psaty, Charles S Decarli, Jennifer A Smith, David C Glahn, Hector M González, Joshua C Bis, Myriam Fornage, Susan R Heckbert, Annette L Fitzpatrick, Chunyu Liu, Claudia L Satizabal

Journal Articles

BACKGROUND AND OBJECTIVES: Previous studies suggest that lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer disease (AD) and AD-related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN with cognitive function and MRI measures in community-based samples of middle-aged to older adults.

METHODS: We included dementia-free participants from 9 diverse community-based cohorts with whole-genome sequencing in the Trans-Omics for Precision Medicine (TOPMed) program. Circulating mtDNA CN was estimated as twice the ratio of the average coverage of mtDNA to nuclear …

Computational Analysis Of Microbial Sequence Data Using Statistics And Machine Learning, Zhixiu Lu

Doctoral Dissertations

Since the discovery of the double helix of DNA in 1953, modern molecular biology has opened the door to a better understanding of how genes control chemical processes within cells, including protein synthesis. Although we are still far from claiming a complete understanding, recent advances in sequencing technologies, increased computational capacity, and more sophisticated computational methods have allowed the development of various new applications that provide further insight into DNA sequence data and how the information they encode impacts living organisms and their environment. Sequencing data can now be used to start identifying the relationships between microorganisms, where they live, …

Dental Calculus: Future In Forensics, Emily Elgin

Chancellor’s Honors Program Projects

No abstract provided.

Role Of Cdx4 And Sp5l In Zebrafish Development, Wesley Tsai

Honors Theses

The Caudal Type Homeobox transcription factors cdx are a family of genes found in vertebrates that regulates body regionalization and anterior-posterior patterning. They are also responsible for regulating axial elongation, but the mechanisms behind this behavior are not known. Previous studies in mouse embryonic stem cells have shown that the cdx genes are necessary for upregulating the gene sp5 which may be linked to axial elongation. Sp5 is a zinc-finger transcription factor belonging to the specificity protein (sp) family. Our group has used in-situ hybridization experiments on zebrafish embryos to show that sp5-like (sp5l) is transcribed within tailbud tissues that …

Sequence Selectivity In The Binding Of Melatonin To Phix174rf Dna, Camila Garcia

FIU Undergraduate Research Journal

Melatonin is an endogenous neurotransmitter that controls the circadian rhythm. When consumed through medication, it has been proven to serve as a treatment for sleep disorders and alleviate sleep quality. Stable levels of melatonin in the human organism are shown to be beneficial as it provides a protective layer to DNA strands ensuring their longevity; however, its excessive consumption may have damaging consequences on the long run. Here we present a study on the sequence selectivity in the binding of melatonin to DNA, intending to show that melatonin targets specific DNA sites. Binding tophiX174RF DNA was assayed using restriction enzyme …

Effects Of Post-Translational Histone Modifications On Transcription Rate, Aaron Bohn, Sarah Hodson, Sarah Ricks, David Bates Ph.D, Steven M. Johnson Ph.D

Library/Life Sciences Undergraduate Poster Competition 2023

The structural organization of DNA in eukaryotic cells is greatly implicated in the regulation of gene expression and thus cellular properties and behavior. At the most fundamental unit of this organization, ~147 bp of DNA wraps 1.7 times around a histone octamer core, forming a collective unit called the nucleosome. The positioning and occupancy of these nucleosomes around the promoter elements of genes is known to be a strong regulator of transcription in eukaryotic nuclei, and post-translational modifications (PTM’s) to the protruding N-terminal tails of histone proteins are known to influence chromatin structure and thus gene expression; however, relatively little …

Dpc29 Promotes Post-Initiation Mitochondrial Translation In Saccharomyces Cerevisiae, Kyle A. Hubble, Michael F. Henry

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Mitochondrial ribosomes synthesize essential components of the oxidative phosphorylation (OXPHOS) system in a tightly regulated process. In the yeast Saccharomyces cerevisiae, mitochondrial mRNAs require specific translational activators, which orchestrate protein synthesis by recognition of their target gene's 5'-untranslated region (UTR). Most of these yeast genes lack orthologues in mammals, and only one such gene-specific translational activator has been proposed in humans-TACO1. The mechanism by which TACO1 acts is unclear because mammalian mitochondrial mRNAs do not have significant 5'-UTRs, and therefore must promote translation by alternative mechanisms. In this study, we examined the role of the TACO1 orthologue in yeast. We …

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Impact Of Sample Conditions On Dna Phosphodiester Backbone Bi/Bii Conformational Equilibrium Dynamics, Autumn C. Pilarski

MSU Graduate Theses

DNA damage, such as single base lesions and mismatches, is highly prevalent within cells. If these DNA damage events are not repaired, they could lead to mutations and thus disease and cancer. Intricate repair mechanisms are in place to fix these damage events, one such being Base Excision Repair (BER) and associated enzyme: Thymine DNA Glycosylase (TDG). The first step of this repair process, recognition of the lesion by TDG, is not well understood. The following thesis presents results to better understand the fundamental biophysical question of how a DNA lesion within a mismatch context is recognized in a million …

Examining The Effect Of Varying Dilutions Of Octopamine On The Gut Microbiome Of Lab-Raised And Wild Acheta Domesticus By Brandon Nelson University Of Puget Sound Biology, Brandon Nelson

Summer Research

For my research I am comparing the gut microbiome of lab raised A. Domesticus that are given various levels of Octopamine, a stress hormone, and comparing that to the gut microbiome of wild cricket types. Crickets are a widely used organism across the world for various experiments as both subject and feed. Knowing how the gut microbiome of these crickets is affected by various levels of stress will allow us to better take care of these crickets. This could also help us determine if there are any diseases that lab raised crickets may be susceptible to. A large part of …

Economic Comparison Of The Relative Costs And Efficiency Of Using Thermo Fisher Scientific Rapidhit™ Id System Versus Traditional Dna Laboratory Analysis, Paul J. Speaker

Faculty & Staff Scholarship

With the emergence of any new technology, economic questions arise regarding the efficacy of the new technology in comparison to existing analytical techniques. While the question of ultimate interest concerns the return on investment (ROI) of the new technology, that ROI requires both an evaluation of the net benefits of the technology and an examination of the costs to implement the technology. In this report, we examine the full-loaded cost structure of traditional DNA analysis using fiscal year 2021 data from Project FORESIGHT and compare the cost per sample with the price structure of the Thermo Fischer Scientific RapidHit technology. …

Taxonomic Classification Of Viral And Bacterial Dna Following 2021 Avian Mass Mortality Event, Tessa Baillargeon

Honors Theses and Capstones

From May through July 2021, an unusual mortality event occurred along the eastern coast and Midwest of the United States. Thousands of birds, mostly from the order Passeriformes, were part of the die-off including blue jays (Cyanocitta cristata), common grackles (Quiscalus quiscula), European starlings (Sturnus vulgaris), American robins (Turdus migratorius). Clinical signs included crusted eyes, swollen conjunctiva, otitis, seizures, and ataxia.

The New Hampshire Veterinary Diagnostic Laboratory (NHVDL) received over 100 affected birds from various collaborators throughout the United States including Washington DC, NJ, CT, MD, and OH. Given the timing and geologic …

Comparing The Microbiomes Of Dental Plaques In 19th Century Ancestral Remains, Ananya Udyaver

Undergraduate Research Posters

During the construction of VCU’s Hermes A. Kontos Medical Sciences Building in April 1994, nineteenth century ancestral remains were found in an abandoned well on the Medical College of Virginia (MCV) campus. This well, now known as the East Marshall Street Well (EMSW), is thought to have been used as a disposal location for cadaver dissection for surgical and other medical waste in the past. VCU is now seeking to use DNA sequencing technology to match and assemble bones from each individual for a proper burial, uncover the cultural and historical context in which these people lived, and bring a …

Fecal Dna Metabarcoding Shows Credible Short-Term Prey Detections And Explains Variation In The Gut Microbiome Of Two Polar Bear Subpopulations, M. Franz, L. Whyte, T. C. Atwood, D. Menning, Sarah A. Sonsthagen, S. L. Talbot, K. L. Laidre, E. Gonzalez, M. A. Mckinney

Nebraska Cooperative Fish and Wildlife Research Unit: Staff Publications

No abstract provided.