Cell and Developmental Biology Commons^™

Surveillance And Stewardship: Where Infection Prevention And Antimicrobial Stewardship Intersect, Fred C. Tenover, Debra A. Goff

Biology Faculty Publications

Colonization with multidrug-resistant organisms (MDROs) is a risk factor for subsequent infection. Surveillance for MDROs, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Enterobacterales, and carbapenemase-producing organisms, is commonly conducted in hospitals to prevent spread of MDROs, in part to reduce the potential for additional infections. Although colonization is a risk factor for infection, data on colonization with various MDROs are often not considered when selecting anti-infective therapy. There are conflicting data on the strength of the positive and negative predictive values of the colonization test results to guide therapeutic strategies. Defining therapeutic strategies for patients with complicated or …

Functional Analysis Provides Insight Into Missing Heritability, Scott L. Baughan, Michael A. Tainsky, Fatima Darwiche

Medical Student Research Symposium

Accurate ascertainment of genetic risk can be potentially lifesaving for patients who inherit cancer promoting mutations. However, even with the most extensive panel testing clinically available, a large number of patients will test negative despite family history of cancer or test positive for a variant of unknown significance (VUS). For these patients, clinical management is complicated; patients want to know their risk, and may fear disease they are not at great risk for (benign VUS) or they may not be given access to potentially lifesaving early screening procedures (pathogenic VUS). ATM has proven a challenge to clinicians due to its …

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …

A Trial Of Fire And Ice: Assessment Of Control Techniques For Pyrus Calleryana Invasion Of Grasslands In Southwestern Ohio, Usa, Margaret E. Maloney, Eric B. Borth, Grace Dietsch, Mary C. Lloyd, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana (Callery pear) is an invasive plant that threatens ecosystems in the eastern United States. We investigated the efficacy of various control techniques on P. calleryana invasion in grasslands. Treatments were applied to (a) P. calleryana stems that had experienced mowing annually for several years and were sprouting (n = 100 stems; “trees-sprouting”) and (b) stems that had established ca. 10 years earlier, had never been cut, and were single-stemmed trees (n = 40 stems; “trees-intact”). In both experiments, existing stems were cut and randomly assigned one of the following treatments: cut only (control), burning, freezing, or herbicide, and …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Directed Carbapenemase Testing Is No Longer Just For Enterobacterales: Cost, Labor, And Workflow Assessment Of Expanding Carbapenemase Testing To Carbapenem-Resistant P. Aeruginosa, Fred C. Tenover, Christian M. Gill, Poonam Rajkotia, Amity L. Roberts, David P. Nicolau

Biology Faculty Publications

Molecular carbapenem-resistance testing, such as for the presence of carbapenemases genes, is commonly implemented for the detection of carbapenemase-producing Enterobacterales. Carbapenemase-producing P. aeruginosa is also associated with significant morbidity and mortality, although; prevalence may be underappreciated in the United States due to a lack of carbapenemase testing. The present study sought to compare hands-on time, cost and workflow implementation of carbapenemase gene testing in Enterobacterales and P. aeruginosa isolates versus sending out isolates to a public health laboratory (PHL) for testing to assess if in-house can provide actionable results. The time to carbapenemase gene results were compared. Differences in cost …

Molecular Regulation Of The Salicylic Acid Hormone Pathway In Plants Under Changing Environmental Conditions, Christina A. M. Rossi, Eric J. R. Marchetta, Jong Hum Kim, Christian Castroverde

Biology Faculty Publications

Salicylic acid (SA) is a central plant hormone mediating immunity, growth, and development. Recently, studies have highlighted the sensitivity of the SA pathway to changing climatic factors and the plant microbiome. Here we summarize organizing principles and themes in the regulation of SA biosynthesis, signaling, and metabolism by changing abiotic/biotic environments, focusing on molecular nodes governing SA pathway vulnerability or resilience. We especially highlight advances in the thermosensitive mechanisms underpinning SA-mediated immunity, including differential regulation of key transcription factors (e.g., CAMTAs, CBP60g, SARD1, bHLH059), selective protein–protein interactions of the SA receptor NPR1, and dynamic phase separation of the recently identified …

Analysis Of A Cathepsin Protease In Normal Development And Tumor Metastasis In Drosophila Melanogaster, Lindsey Fannin

Mahurin Honors College Capstone Experience/Thesis Projects

Cysteine cathepsins are an important class of fifteen proteases with involvement in normal development and tumor progression. To better understand their contribution to these processes, the cathepsin L protease in Drosophila melanogaster was studied. In part one of this project, the role of this cathepsin in the normal development of Drosophila wings was analyzed. The GAL4/UAS-system and RNAi were used to downregulate this cathepsin in various regions of the wing and progeny were inspected for phenotypic irregularities. An abnormal phenotype of curved wings was found and hypothesized to be a result of apoptosis. Further experimentation will be required to prove …

Dna Methylation And The Response To Infection In Introduced House Sparrows, Melanie Gibson

College of Graduate Studies: Theses & Dissertations

Epigenetics is the study of molecular modification of a genome without changing its base pairs. The most studied type of epigenetic mechanism is DNA methylation, which is capable of turning a gene “on” or “off.” Epigenetic potential is the capacity to which an individual can have methylation on its genome. The more CpGs available, the greater the epigenetic potential. In invasive species, genetic variation has been observed to be paradoxical: not much of it exists on a genomic level, but epigenetically, phenotypic variation can occur. The focus on shift in gene expression in this study is on Toll-Like Receptor 4 …

Revolutionary Advances In The Treatment Of Genetic Disease, Emma Kaitlyn Carrigan

Honors Theses and Capstones

No abstract provided.

Cell Signaling And Stress Response In The Yeast Saccharomyces Cerevisiae: A Study Of Snf1, Scott E. Arbet Ii

Graduate Theses, Dissertations, and Problem Reports (ETD)

Saccharomyces cerevisiae are yeast that are unicellular eukaryotic organisms that are well studied as a model organism for understanding fundamental cellular processes. The ability of yeast to sense nutrient availability is crucial for their survival, growth, and reproduction. Yeast cells use various mechanisms to sense and respond to nutrient availability, including transporter-mediated uptake, receptor-mediated signaling, and sensing of metabolites. The subcellular localization of nutrient-sensing components is crucial for yeast function in nutrient sensing and signaling. Protein complexes, such as the AMP-activated protein kinase (AMPK) pathway, in nutrient sensing and response, as well as the downstream effects of these pathways …

Unusual Chromosome Configurations: Evaluation Of Sex Univalent And Trivalent Chromosome Models, Ashley B. Borseth

Master’s Theses

Aneuploidy, or abnormal number of chromosomes in a haploid set, in XY/XX organisms has consequences that can impede physical and cognitive development. To prevent aneuploidy, cellular division relies on the correct position of paired chromosomes and subsequent segregation in the meiotic program. If connections between paired chromosomes sever or errors in chromosome contraction towards spindle poles arise, aneuploidy occurs. Many arthropod species have chromosomes that naturally do not pair, or that pair differently than typical autosomes. Through the evaluation of such systems, novel insights into chromosomal coordination and positioning may be revealed. The objective of this study is twofold: (1) …

Knockout Of Endospanin 1 Via Crispr In Zebrafish, Danio Rerio, Jared Kittinger

Williams Honors College, Honors Research Projects

I made endospanin 1 knockout (KO) zebrafish to examine its effects on lipid and bone metabolism. Endospanin 1, or leptin receptor overlapping transcript (leprot), is a cytosolic protein linked to the protein hormone leptin that influences the trafficking of leptin receptors to the plasma membrane of cells. Genes for endospanin and tyrosinase (a pigmentation enzyme) were targeted via a microinjection of guide RNAs and CRISPR Cas9 into zebrafish embryos at 2-4 cell stages. I was able to disrupt the endospanin 1 gene (based upon the disruption of tyrosinase), but very few mutant zebrafish fully developed into adults. Only low KO …

Dysregulated Polycomb Repressive Complex 2 Contributes To Chronic Obstructive Pulmonary Disease By Rewiring Stem Cell Fate, Aria Byrd, Xufeng Qu, Alexsandr Lukyanchuk, Jinpeng Liu, Fan Chen, Kassandra J. Naughton, Tanner Ducote, Xiulong Song, Hannah Bowman, Yanming Zhao, Abigail R Edgin, Chi Wang, Jinze Liu, Christine Fillmore Brainson

Markey Cancer Center Faculty Publications

Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self- renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 …

Med12 Is A Critical Regulator Of Neural Crest Lineage And Nervous System Myelination, Fatma Betul Aksoy Yasar

Dissertations and Theses (Open Access)

The Mediator complex (MED) is a multi-subunit protein complex integral to the eukaryotic transcription machinery. MED12 is a Cdk8- regulatory kinase module subunit directly implicated in human disease and is genetically altered in neurological disease and cancer. Numerous attempts at generating an in vivo system to study the role of Med12 failed due to embryonic lethality associated with germline or developmental disruption of Med12 gene. To understand the cellular and molecular processes associated with its role in disease, we generated multiple mouse models with targeted depletion of MED12 in distinct cellular lineages. Our genetically engineered models with induced and conditional …

Npgreat: Assembly Of The Human Subtelomere Regions With The Use Of Ultralong Nanopore Reads And Linked Reads, Eleni Adam, Desh Ranjan, Harold Riethman

Computer Science Faculty Publications

Background: Human subtelomeric DNA regulates the length and stability of adjacent telomeres that are critical for cellular function, and contains many gene/pseudogene families. Large evolutionarily recent segmental duplications and associated structural variation in human subtelomeres has made complete sequencing and assembly of these regions difficult to impossible for many loci, complicating or precluding a wide range of genetic analyses to investigate their function.

Results: We present a hybrid assembly method, NanoPore Guided REgional Assembly Tool (NPGREAT), which combines Linked-Read data with mapped ultralong nanopore reads spanning subtelomeric segmental duplications to potentially overcome these difficulties. Linked-Read sets of DNA sequences identified …

A Pooling Strategy For Detecting Carbapenem Resistance Genes By The Xpert Carba-R Test In Rectal Swab Specimens, Fred C. Tenover, Peng Zhang, Qi Wang, Chaoe Zhou, Feifei Zhang, Xinghui Gao, Yi-Wei Tang, Hui Wang

Biology Faculty Publications

Rapid and accurate detection of carriers of carbapenemase-producing organisms (CPO) in hospitalized patients is critical for infection control and prevention. This study aimed to evaluate a pooling strategy for the detection of carbapenem resistance genes (CRG) in multiple specimens using the Xpert Carba-R test. Two rectal swabs each were collected from 415 unique patients. One swab was tested by Carba-R on the five specimen-pooled strategy. The other swab was tested individually by culture followed by DNA sequence analysis for CRG as the reference. At the first 5:1 pooling testing, 22 of 83 pools were positive, which yielded 34 positives from …

Cell Size Control Mechanisms In The Multiple Fission Cell Cycle Of Chlamydomonas, Dianyi Liu

Dissertations

Size homeostasis is achieved by a balance between cell growth and cell division, but the underlying mechanisms are yet fully understood. Green alga Chlamydomonas reinhardtii (Chlamydomonas) is a unique model for size control. Instead of the canonical binary fission cell cycle, Chlamydomonas uses a multiple fission cell cycle where a prolonged G1 phase is followed by rapid alternative n rounds of S/M (DNA synthesis and mitosis) cycles to produce 2ⁿ daughter cells. Two size checkpoints show size-dependence: the Commitment checkpoint governs a minimum size for a cell to divide at least once, and the S/M checkpoint governs the division …

Temporal Trends In Lipoprotein(A) Concentrations: The Atherosclerosis Risk In Communities Study, Matthew R. Deshotels, Caroline Sun, Vijay Nambi, Salim S. Virani, Kunihiro Matsushita, Bing Yu, Christie . M. Ballantyne, Ron C. Hoogeveen

Office of the Provost

Background: Plasma lipoprotein(a) (Lp[a]) concentrations are primarily determined by genetic factors and are believed to remain stable throughout life. However, data are scarce on longitudinal trends in Lp(a) concentrations over time. Therefore, it is unclear whether measurement of Lp(a) once in a person's life is sufficient for cardiovascular risk assessment in all adults.
Methods and Results: Lp(a) concentrations, specifically apolipoprotein(a) concentrations, were measured at visits 4 and 5, ≈15 years apart, in 4734 adult participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age at visits 4 and 5, 60.7±5.1 and 75.5±5.2 years, respectively). Participants were categorized by baseline …

Ngly1 Deficiency Affects Glycosaminoglycan Biosynthesis And Wnt Signaling Pathway In Mice, Amy Batten

PANDION: The Osprey Journal of Research and Ideas

Individuals affected by NGLY1 Deficiency cannot properly deglycosylate and recycle certain proteins. Even though less than 100 people worldwide have been diagnosed with this rare autosomal recessive condition, thousands are affected by similar glycosylation disorders. Common phenotypic manifestations of NGLY1 Deficiency include severe neural and intellectual delay, impaired muscle and liver function, and seizures that may become intractable. Very little is currently known about the various mechanisms through which NGLY1 deficiency affects the body and this has led to a lack of viable treatment options for those afflicted. This experiment uses a loss-of-function (LOF) mouse model of NGLY1 Deficiency homologous …

The Genetics Of Skin Cancer: What Genes Drive The Development Of Basal Cell Carcinoma, Squamous Cell Carcinoma, And Melanoma?, Cassandra Poole, Abagail Pack, Elizabeth Whitehead, Virginia Marshall

Fall Showcase for Research and Creative Inquiry

Skin cancer is one of the most common forms of cancer worldwide. The American Academy of Dermatology estimates that 9500 people in the United States are diagnosed with skin cancer every day, and that 1 in 5 Americans will be diagnosed with skin cancer by age 70. With such a high prevalence of disease, understanding how skin cancer develops and how it can be treated is extremely important. This project aims to analyze the genes involved in the development of the three most common forms of skin cancer: basal cell carcinoma, squamous cell carcinoma, and melanoma.

Leaf Phenology And Freeze Tolerance Of The Invasive Tree Pyrus Calleryana (Roseaceae) And Potential Native Competitors, Margaret E. Maloney, Abby Hay, Eric B. Borth, Ryan W. Mcewan

Biology Faculty Publications

Pyrus calleryana is one of the most problematic invasive species in the eastern United States. The mechanisms that enable Py. calleryana to establish and outcompete native plants are not fully understood but likely include a profile of advantageous traits. Extended leaf phenology is a characteristic noted in many woody invasive plants. Leaf phenology of Py. calleryana and two native woody species, Populus deltoides and Platanus occidentalis, was observed in natural areas near Dayton, OH from December 2019 to November 2020. A frost event in May also gave us the serendipitous opportunity to assess frost tolerance of these species. We …

Mechanisms Of Carbapenemase-Mediated Resistance Among High-Risk Pseudomonas Aeruginosa Lineages In Peru, Isabella A. Tickler, Juan Carlos Gomez De La Torre, Luis Alvarado, Anne E. Obradovich, Fred C. Tenover

Biology Faculty Publications

Objectives: Pseudomonas aeruginosa is one of the leading causes of healthcare-associated infections globally. High-risk carbapenemase-encoding P. aeruginosa clones are disseminating in many regions. The aim of this study was to learn more about the lineages and mechanisms of resistance of P. aeruginosa circulating in Peru.

Methods: A total of 141 carbapenemase-producing isolates recovered from hospitalized and ambulatory patients in Lima were sequenced and analyzed to infer their lineages through whole-genome sequence typing (wgST) and to identify their antimicrobial resistance genes.

Results: wgST identified nine sequence types (STs); ST111 and ST357 were the most frequently encountered (44.0% and 38.3%, respectively), followed …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Heat Stress Response And Excystation In Entamoeba Histolytica, Irem Bastuzel

All Dissertations

Entamoeba histolytica is a water- and food-borne intestinal protozoan parasite that causes amoebiasis and liver abscess and is responsible for symptomatic disease in approximately 100 million people each year leading to ~ 100,000 deaths. The most common disease transmission follows the oral-fecal route, but it can also be transmitted by mechanical vectors such as animals carrying the amoeba from contaminated sources to water systems. In rare cases, disease transmission has been recorded in some patients in which men-to-men sexual practices were preferred.

The life cycle of E. histolytica starts through ingestion of infectious cysts, which are non-dividing, quadri-nucleated structures surrounded …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

University Scholar Projects

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Functional Role Of Ppal And Potential For Moss In Industrial Applications., Susana Perez Martinez

Electronic Theses and Dissertations

This dissertation is an examination and characterization of the functional roles of PPAL. PROTEIN PRENYLTRANSFERASE ALPHA SUBUNIT-LIKE (PPAL) is a recently discovered gene. PPAL homologs are present in all plants and many animals, where its function is largely unknown. It is possible that PPAL could participate in prenylation processes since it shares similarity to the α subunits of known prenylation enzymes. Prenylation is a post-translational modification of proteins that involves the addition of a lipid moiety to proteins to facilitate membrane targeting and association and promote protein-protein interactions. Prenylation has important roles in plant growth and development, including …

When Problems Become Solutions: Harnessing The Osteogenic Capacity Of Disease-Causing Stem Cells To Repair Bone Fractures, Mehreen Pasha

Honors Scholar Theses

While we often perceive disease as negative, there is potential to engineer seemingly negative biological phenomena into therapeutics to treat a variety of human illnesses. Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder involving uncontrolled, widespread, extraskeletal bone growth, or heterotopic ossification (HO). In FOP patients, stem cells called fibro/adipogenic progenitors (FAPs) follow an abnormal, osteogenic pathway. In the present study, we investigate whether we can adapt these Acvr1 mutant FAPs, which are exceptional at producing bone, to repair bone fractures in otherwise normal patients. The primary aims of this study are (1) to devise and optimize a novel method …

Unraveling The Genetic Architecture Of Somatic Embryogenesis In Upland Cotton, Adam M. Canal

All Theses

Somatic embryogenesis is the de novo development of asexual embryos because of the plasticity of the plant cell. In tissue culture, the biochemical and genetic mechanisms of dedifferentiated callus tissues can be reprogrammed to transdifferentiate into developed, polarized embryos, which can ultimately regenerate into whole plants. Although this rarely occurs in nature, scientists have exploited this process for decades to regenerate whole plants following gene transformation or for micropropagation. While some species are amenable to in vitro regeneration, upland cotton is particularly recalcitrant, with regenerative potential being confined to only several genotypes. The lack of elite, regenerable genotypes greatly restricts …