Genetics and Genomics Commons^™

Genomic Epidemiology Of Clostridium Difficile Colonization And Transmission In An Intensive Care Unit Cohort, Brianne Ciferri

Dissertations and Theses

Abstract

Genomic epidemiology of Clostridium difficile colonization and transmission in an intensive care unit cohort

by Brianne Ciferri, MPH

Advisor: C. Mary Schooling, PhD

Introduction: Clostridiodes difficile (C. difficile) is a leading cause of healthcare associated infections (HAI) in the United States and responsible for an estimated incidence of 223,900 cases and 12,800 deaths per year^1,2. C. difficile can cause gastrointestinal illness with symptoms ranging from mild diarrheal illness to a life-threatening condition. C. difficile is an opportunistic pathogen in which spores can live in an undisturbed dormant state within the intestinal tract and become …

A Dystrophin Exon‐52 Deleted Miniature Pig Model Of Duchenne Muscular Dystrophy And Evaluation Of Exon Skipping, Yusuke Echigoya, Nhu Trieu, William Duddy, Hong M. Moulton, Haifang Yin, Terence A. Partridge, Eric P. Hoffman, Joe N. Kornegay, Frank A. Rohret, Christopher S. Rogers, Toshifumi Yokota

Genomics and Precision Medicine Faculty Publications

No abstract provided.

Mutant Kras Alters Extracellular Vesicle Microrna Sorting In Pancreatic Cystic Neoplasms, Rachel L. Dittmar

Dissertations & Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers by organ site with a 5-year survival rate of just 10.8%. This is largely because most patients do not experience symptoms until the disease has already metastasized. The best hope to cure PDAC is surgery, which can only be done with a curative intent at an early stage when the disease is localized. There are no reliable circulating, body-fluid-based biomarkers to detect early stage PDAC or its precursor lesions in a timely manner for effective surgical intervention. When potential PDAC precursor lesions, such as mucinous pancreatic cysts are found, there are …

Deciphering The Role Of Hsp110 Chaperones In Diseases Of Protein Misfolding, Unekwu M. Yakubu

Dissertations & Theses (Open Access)

Molecular chaperones maintain protein homeostasis (proteostasis) by ensuring the proper folding of polypeptides. Loss of proteostasis has been linked to the onset of numerous neurodegenerative disorders including Alzheimer’s, Parkinson’s, and Huntington’s disease. Hsp110 is a member of the Hsp70 class of molecular chaperones and acts as a nucleotide exchange factor (NEF) for Hsp70, the preeminent Hsp70-family protein folding chaperone. Hsp110 promotes rapid cycling of ADP for ATP, allowing Hsp70 to properly fold nascent or unfolded polypeptides in iterative cycles. In addition to its NEF activity, Hsp110 possesses an Hsp70-like substrate binding domain (SBD) whose biological roles are undefined. Previous work …

Using Artificial Intelligence To Decipher Epigenetic Code Of Drug Resistance In The Deadliest Human Malaria Parasite, Samira Jahangiri

USF Tampa Graduate Theses and Dissertations

Malaria remains one of the immense global public health challenges, with an estimated ~200 million cases worldwide in 2019 despite the remarkable gains in reducing this deadly disease over the past decade. The recent emergence and spread of artemisinin resistance (ART-R) in Plasmodium falciparum will increasingly impede global efforts to control and eliminate malaria. Previous studies have observed broad transcriptional changes and identified several noncoding genetic variants strongly associated with ART-R. The broad transcriptional variations suggest that the malaria parasite uses sophisticated epigenetic regulation to survive under drug pressure. Therefore, evaluating the regulatory effects of noncoding-variants in malaria parasites is …

Comparison Of Multiple Imputation Algorithms And Verification Using Whole-Genome Sequencing In The Cmuh Genetic Biobank, Ting-Yuan Liu, Chih-Fan Lin, Hsing-Tsung Wu, Ya-Lun Wu, Yu-Chia Chen, Chi-Chou Liao, Yu-Pao Chou, Dysan Chao, Hsing-Fang Lu, Ya-Sian Chang, Jan-Gowth Chang, Kai-Cheng Hsu, Fuu‑Jen Tsai

BioMedicine

A genome-wide association study (GWAS) can be conducted to systematically analyze the contributions of genetic factors to a wide variety of complex diseases. Nevertheless, existing GWASs have provided highly ethnic specific data. Accordingly, to provide data specific to Taiwan, we established a large-scale genetic database in a single medical institution at the China Medical University Hospital. With current technological limitations, microarray analysis can detect only a limited number of single-nucleotide polymorphisms (SNPs) with a minor allele frequency of >1%. Nevertheless, imputation represents a useful alternative means of expanding data. In this study, we compared four imputation algorithms in terms of …

Editorial For The Genetics Of Alzheimer’S Disease Special Issue: October 2021, Laura Ibanez, Justin B. Miller

Sanders-Brown Center on Aging Faculty Publications

No abstract provided.

Genomics Of Postprandial Lipidomics In The Genetics Of Lipid-Lowering Drugs And Diet Network Study, Marguerite R. Irvin, May E. Montasser, Tobias Kind, Sili Fan, Dinesh K. Barupal, Amit Patki, Rikki M. Tanner, Nicole D. Armstrong, Kathleen A. Ryan, Steven A. Claas, Jeffrey R. O’Connell, Hemant K. Tiwari, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled …

Decoding The Equine Genome: Lessons From Encode, Sichong Peng, Jessica L. Petersen, Rebecca R. Bellone, Theodore S. Kalbfleisch, N. B. Kingsley, Alexa M. Barber, Eleonora Cappelletti, Elena Giulotto, Carrie J. Finno

Veterinary Science Faculty Publications

The horse reference genome assemblies, EquCab2.0 and EquCab3.0, have enabled great advancements in the equine genomics field, from tools to novel discoveries. However, significant gaps of knowledge regarding genome function remain, hindering the study of complex traits in horses. In an effort to address these gaps and with inspiration from the Encyclopedia of DNA Elements (ENCODE) project, the equine Functional Annotation of Animal Genome (FAANG) initiative was proposed to bridge the gap between genome and gene expression, providing further insights into functional regulation within the horse genome. Three years after launching the initiative, the equine FAANG group has generated data …

Improved Radiation Expression Profiling In Blood By Sequential Application Of Sensitive And Specific Gene Signatures, Eliseos J. Mucaki, Ben C. Shirley, Peter K. Rogan

Biochemistry Publications

Purpose. Combinations of expressed genes can discriminate radiation-exposed from normal control blood samples by machine learning based signatures (with 8 to 20% misclassification rates). These signatures can quantify therapeutically-relevant as well as accidental radiation exposures. The prodromal symptoms of Acute Radiation Syndrome (ARS) overlap those present in Influenza and Dengue Fever infections. Surprisingly, these human radiation signatures misclassified gene expression profiles of virally infected samples as false positive exposures. The present study investigates these and other confounders, and then mitigates their impact on signature accuracy.

Methods. This study investigated recall by previous and novel radiation signatures independently derived …

Global Gene Expression Analysis Of Systemic Sclerosis Myofibroblasts Demonstrates A Marked Increase In The Expression Of Multiple Nbpf Genes, Giuseppina Abignano, Heidi Hermes, Sonsoles Piera-Velazquez, Sankar Addya, Francesco Del Galdo, Sergio A. Jimenez

Kimmel Cancer Center Faculty Papers

Myofibroblasts are the key effector cells responsible for the exaggerated tissue fibrosis in Systemic Sclerosis (SSc). Despite their importance to SSc pathogenesis, the specific transcriptome of SSc myofibroblasts has not been described. The purpose of this study was to identify transcriptome differences between SSc myofibroblasts and non-myofibroblastic cells. Alpha smooth muscle actin (α-SMA) expressing myofibroblasts and α-SMA negative cells were isolated employing laser capture microdissection from dermal cell cultures from four patients with diffuse SSc of recent onset. Total mRNA was extracted from both cell populations, amplified and analyzed employing microarrays. Results for specific genes were validated by Western blots …

Effects Of Hormone Replacement Therapy (Hrt) On Gene Expression In The Amyloid Processing Pathway Of Ovariectomized Rhesus Macaque Females Under An Obesogenic Diet, Megan Ball

University Honors Theses

Estrogens rapidly decline at the onset of menopause, putting women at higher risk of osteoporosis, obesity, and neurodegenerative diseases, including Alzheimer’s disease (AD). Estradiol hormone therapies (HT) have been suggested to limit these negative effects on women, with controversial findings as to their effectiveness. A study at OHSU recently found differentially expressed genes (DEGs) using RNAseq between ovariectomized/hysterectomized (OvH) old (range = 19.4–23.2 years) female rhesus macaques on HT and those on a placebo on chronic western style diet (WSD). The DEGs identified in the amyloid processing pathway of the amygdala were selected for validation using RT-qPCR because β-amyloid peptide …

An Enhancement To Cnn Approach With Synthesized Image Data For Disease Subtype Classification, Narider Pal Singh

Electronic Theses and Dissertations

The introduction of genetic testing has profoundly enhanced the prospects of early detection of diseases and techniques to suggest precision medicines. The subtyping of critical diseases has proven to be an essential part of the development of individualized therapies and has led to deeper insights into the heterogeneity of the disease. Studies suggest that variants in particular genes have significant effects on certain types of immune system cells and are also involved in the risk of certain critical illnesses like cancer. By analyzing the genetic sequence of a patient, disease types and subtypes can be predicted. Recent research work has …

Where Epigenetics Meets Food Intake: Their Interaction In The Development/Severity Of Gout And Therapeutic Perspectives, Philippe T. Georgel, Philippe Georgel

Biological Sciences Faculty Research

Gout is the most frequent form of inflammatory arthritis in the world. Its prevalence is particularly elevated in specific geographical areas such as in the Oceania/Pacific region and is rising in the US, Europe, and Asia. Gout is a severe and painful disease, in which co-morbidities are responsible for a significant reduction in life expectancy. However, gout patients remain ostracized because the disease is still considered “self-inflicted”, as a result of unhealthy lifestyle and excessive food and alcohol intake. While the etiology of gout flares is clearly associated with the presence of monosodium urate (MSU) crystal deposits, several major questions …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Informed Consent: Foundations And Applications, Joanna Smolenski

Dissertations, Theses, and Capstone Projects

Since its advent in the 20th century, informed consent has become a cornerstone of ethical healthcare, and obtaining it a core obligation in medical contexts. In my dissertation, I aim to examine the theoretical underpinnings of informed consent and identify what values it is taken to protect. I will suggest that the fundamental motivation behind informed consent rests in something I’ll call bodily self-sovereignty, which I argue involves a coupling of two groups of values: autonomy and non-domination on the one hand, and self-ownership and personal integrity on the other. I will then go on to consider two 'case …

Higher Entropy Observed In Sars-Cov-2 Genomes From The First Covid-19 Wave In Pakistan, Najia Karim Ghanchi, Asghar Nasir, Kiran I. Masood, Syed Hani Abidi, Syed Faisal Mahmood, Akber Kanji, Safina Abdul Razzak, Waqasuddin Khan, Saba Shahid, Maliha Yameen, Ali Raza, Javaria Ashraf, Zeeshan Ansar Ahmed, Mohammad Buksh Dharejo, Nazneen Islam, Zahra Hasan, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: We investigated the genome diversity of SARS-CoV-2 associated with the early COVID-19 period to investigate evolution of the virus in Pakistan.
Materials and methods: We studied ninety SARS-CoV-2 strains isolated between March and October 2020. Whole genome sequences from our laboratory and available genomes were used to investigate phylogeny, genetic variantion and mutation rates of SARS-CoV-2 strains in Pakistan. Site specific entropy analysis compared mutation rates between strains isolated before and after June 2020.
Results: In March, strains belonging to L, S, V and GH clades were observed but by October, only L and GH strains were present. The …

The Role Of Pannexin 3 In Forced Exercise Bone Remodelling And Its Potential Implications For Osteoarthritis, Justin Tang

Undergraduate Student Research Internships Conference

Exercise such as running has been hypothesized to be a factor of osteoarthritis development. However, the relationship is unclear as differences in genetic backgrounds may influence the risk of osteoarthritis (OA). The gene Panx3 codes for the Pannexin 3 protein (PANX3), a mechanically sensitive channel that allows for the passage of various signalling molecules in both chondrocytes and osteoblasts (Boassa et al., 2007; Penuela et al., 2013; Zhang et al., 2021). We have previously shown PANX3 to be protective in traumatic osteoarthritis, however beneficial in age-induced osteoarthritis (Moon et al., 2021), suggesting that PANX3’s role in osteoarthritis development …

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

Discovery Of Sex Differences In Response To P53 Loss And Gain-Of-Function In Glioblastoma, Nathan Cuyle Rockwell

Arts & Sciences Electronic Theses and Dissertations

The tumor suppressor TP53 (p53) is the most frequently mutated gene in cancer and among the most mutated genes in brain cancer. Functionally, p53 is a transcription factor that, when activated by an array of stress stimuli, regulates a complex transcriptional program that contributes to a variety of antiproliferative pathways. The loss of p53 function (LOF), either through mutation, deletion, or inhibition by alterations in the proteins that regulate p53, removes an essential barrier to the unfettered proliferation and genomic instability that drive transformation. Unlike most tumor suppressors, many p53 mutations are missense mutations that lead to stable expression of …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

Anatomy And Physiology Preparatory Course Textbook (2nd Edition), Carlos Liachovitzky

Open Educational Resources

The goal of this preparatory textbook is to give students a chance to become familiar with some terms and some basic concepts they will find later on in the Anatomy and Physiology course, especially during the first few weeks of the course.

Organization and functioning of the human organism are generally presented starting from the simplest building blocks, and then moving into levels of increasing complexity. This textbook follows the same presentation. It begins introducing the concept of homeostasis, then covers the chemical level, and later on a basic introduction to cellular level, organ level, and organ system level. This …

Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche

Pharmaceutical Sciences (MS) Theses

Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells (HMECs) were …

Effects Of Trans-Acting Factors On The Translational Machinery In Yeast, Brandon M. Trainor

Graduate School of Biomedical Sciences Theses and Dissertations

Synthesis of proteins, or translation, is a complex biological process requiring the coordinated effort of numerous protein and RNA factors. Central to translation is the ribosome, a complex macromolecular complex consisting of both ribosomal RNA (rRNA) and ribosomal protein (r-protein). Ribosomes are essential and are one of the oldest and most abundant biomolecules across all forms of life. In addition to the ribosome, translation requires messenger RNA (mRNA), transfer-RNA conjugated to an amino acid (aa-tRNA), translation factors, and energy in the form of ATP and GTP. Translation universally occurs in four major stages, initiation, elongation, termination, and recycling, with initiation …

Understanding The Pathogenesis Of Renal Medullary Carcinoma, Melinda Soeung

Dissertations & Theses (Open Access)

Renal medullary carcinoma (RMC) is a lethal cancer that predominantly affects young individuals with sickle cell trait (SCT). It is not currently understood why RMC only affects certain individuals with SCT. We found that patients with RMC more frequently participated in high-intensity exercise than matched controls. Using mouse models of SCT, we demonstrated the significant increase of renal hypoxia in the right kidney following high- but not moderate-intensity exercise. We also demonstrated in cell culture studies that SMARCB1 is ubiquitinated for proteasome-mediated degradation in hypoxia, and the re-expression of SMARCB1 leads to compromised proliferation in renal cells specifically in the …

Epithelial Memory Of Resolved Inflammation Limits Tissue Damage While Promoting Pancreatic Tumorigenesis, I-Lin Ho

Dissertations & Theses (Open Access)

Inflammation is a major risk factor for pancreatic ductal adenocarcinoma. When occurring in the context of pancreatitis, mutations of KRAS accelerate tumor development. We discovered that long after its complete resolution, a transient inflammatory event primes pancreatic epithelial cells to subsequent transformation by oncogenic KRAS. Upon recovery from acute inflammation, epithelial cells of the pancreas display an enduring adaptive response associated with sustained transcriptional and epigenetic reprogramming. Such adaptation enables the prompt reactivation of acinar-to-ductal metaplasia (ADM) upon subsequent inflammatory events, thus efficiently limiting tissue damage via rapid decrease of zymogen production. We propose that since activating mutations of KRAS …

Deciphering The Perpetual Fight Between Virus And Host: Utilizing Bioinformatics To Elucidate The Host's Genetic Mechanisms That Influence Jc Polyomavirus Infection, Michael P. Wilczek

Electronic Theses and Dissertations

JC polyomavirus (JCPyV) is a human-specific pathogen that infects 50-80% of the population, and can cause a deadly, demyelinating disease, known as progressive multifocal leukoencephalopathy (PML). In most of the population, JCPyV persistently infects the kidneys but during immunosuppression, it can reactivate and spread to the central nervous system (CNS), causing PML. In the CNS, JCPyV targets two cell types, astrocytes, and oligodendrocytes. Due to the hallmark pathology of oligodendrocyte lysis observed in disease, oligodendrocytes were thought to be the main cell type involved during JCPyV infection. However, recent evidence suggests that astrocytes are targeted by the virus and act …

Understanding The Role Of Arglu1 In Interferon Signaling Activation In Breast Cancer, Phuoc Nguyen

Dissertations & Theses (Open Access)

In the U.S., the highest number of new cancer cases belongs to breast cancer in women, and this cancer also bears the second-highest death rate in women. Despite significant progress in breast cancer treatment that has been made in the past several decades, innovative and efficient therapies are still needed to eradicate this deadly disease. Novel cancer immunotherapy with immune checkpoint blockade (ICB) could induce long-lasting responses and improve survival in hard-to-treat malignancies. Regrettably, only a fraction of breast cancer patients respond to this highly promising strategy. To improving ICB therapy in breast cancer treatment, IFN signaling induction is a …

Unveiling Global Roles Of G-Quadruplexes And G4-22 In Human Genetics, Ruth Barros De Paula

Dissertations & Theses (Open Access)

G-quadruplexes are non-B DNA structures formed by four or more runs of repeated guanines that confer unique features to living organism’s genomes. These sequences are enriched in regulatory regions, such as promoters and 5’ UTRs, and have distinct regulatory roles in both health and disease states. Even though previous studies showed the impact of G4 in gene expression, none of them summarized the location-specific effect of G4. Also, there is no broad understanding about the most common G4 repeat in the human genome, named here as G4-22, and how it links to the evolution of mammals and their biology. In …