Genetics Commons^™

Therapeutic Potential Of Astrocyte-Derived Extracellular Vesicles In Mitigating Cytotoxicity And Transcriptome Changes In Human Brain Endothelial Cells, Ruth Juliana Stewart

Doctoral Dissertations

Extracellular vesicles (EVs) play a major role in cell-to-cell communication via the horizontal transfer of RNA, DNA, proteins, and lipids that affect the physiological response of the recipient cells. Astrocytes are a type of glial cell that exerts a protective effect on neurons and brain endothelial cells. The astrocytes and the endothelial cells form the blood-brain barrier. Due to their nano-size and non-complex structure, EVs can efficiently cross the blood-brain barrier. This study investigated and assessed the impact of EVs on reducing oxidative DNA damage in human brain endothelial cells (HBECs). The protective potential of astrocyte-derived EVs was determined by …

Analyzing And Extending Machine Learning Frameworks On High Risk Domains, Chengbin Hu

USF Tampa Graduate Theses and Dissertations

Machine learning (ML) has become a transformative force in high-risk domains such as genomics and cybersecurity, where accurate predictions and robust defenses are essential. This dissertation advances ML frameworks in these areas by developing methods to enhance predictive power in health applications and assess vulnerabilities in machine learning systems.

In the genomics field, the work addresses challenges in Non-Invasive Prenatal Testing (NIPT) of monogenic disorders by proposing a deep learning model that reconstructs the fetal genome using maternal plasma cell-free DNA (cfDNA) and parental whole-genome sequencing (WGS) data. This model achieves high accuracy in single nucleotide variation (SNV) prediction, surpassing …

Engineering The Coherent Phonon Transport In Polar Ferromagnetic Oxide Superlattices, In Hyeok Choi, Seung Gyo Jeong, Do-Gyeom Jeong, Ambrose Seo, Woo Seok Choi, Jong Seok Lee

Chemical and Materials Engineering Faculty Publications

Artificial superlattices composed of perovskite oxides serves as an essential platform for engineering coherent phonon transport by redefining the lattice periodicity, which strongly influences the lattice-coupled phase transitions in charge and spin degrees of freedom. However, previous methods of manipulating phonons have been limited to controlling the periodicity of superlattice, rather than utilizing complex mutual interactions that are prominent in transition metal oxides. In this study on oxide superlattices composed of ferromagnetic metallic SrRuO3 and quantum paraelectric SrTiO3 , phonon modulation by controlling the geometry of superlattice in atomic-scale precision is realized, demonstrating the coherent phonon engineering using structural and …

Repeated Shifts In Sociality Are Associated With Fine-Tuning Of Highly Conserved And Lineage-Specific Enhancers In A Socially Flexible Bee, Beryl M. Jones, Andrew E. Webb, Scott M. Geib, Sheina Sim, Rena M. Schweizer, Michael G. Branstetter, Jay D. Evans, Sarah D. Kocher

Entomology Faculty Publications

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used self-transcribing active regulatory region sequencing, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from 3 social and 3 solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers …

A Long-Recognized But Undescribed New Species Of Cyprinella (Cypriniformes: Leuciscidae) From North Carolina And South Carolina, United States, Bryn H. Tracy, Fred C. Rohde, Michael A. Perkins, Laura M. Lee, Kara B. Carlson, Madelyn Mccutcheon, Brena K. Jones, Heather K. Evans

Southeastern Fishes Council Proceedings

Cyprinella leptocheilus sp. nov., Siouan Thinlip Chub, is described as a new species that is endemic to Sand Hills and upper Coastal Plain streams in North Carolina and South Carolina. Recognized as an undescribed species since the early 1970s, this fish was known in the literature and in museum electronic databases as Hybopsis n. sp., H. sp. cf. zanema, Cyprinella n. sp., and C. sp. cf. zanema. Unofficially, it had gone by the common name Thinlip Chub. It was thought to be closely related to the two other barbeled Cyprinella species: Thicklip Chub, …

Unravelling The Impact Of Blood Metabolites, And Lifestyle Factors On Periodontal Disease Using Mendelian Randomization, Rhea Charles

USF Tampa Graduate Theses and Dissertations

Periodontal disease remains a global public health concern. Despite the availability of preventive and therapeutic strategies, the multifactorial nature of periodontitis complicates its understanding and management. Periodontal disease is associated with an increased risk of chronic conditions, including ischemic heart disease (IHD), gestational hypertension, respiratory diseases such as COPD and bronchitis, and various cancers, including kidney and pancreatic cancers. Moreover, individuals with diabetes, autoimmune diseases like lupus and Crohn’s disease, and osteoporosis are more likely to develop periodontitis. The ambiguity in the direction of causality between periodontal disease and its associated conditions poses challenges for effective treatment. Mendelian randomization offers …

The Short Allele Of The Serotonin Transporter Gene (Slc6a4) Increases Predisposition To Anxiety And Negative Emotional States, Gabriella Hitti

PANDION: The Osprey Journal of Research and Ideas

Mental disorders, such as anxiety and mood disorders, have long been a focus of psychological research, and increasing evidence points to a genetic basis for their occurrence. Polymorphisms of the serotonin transporter (5-HTT) gene (SLC6A4) may predispose an individual to anxiety-related symptoms. SLC6A4 has two common alleles: the short (s) allele, which results in less 5-HTT protein production, and the long (l) allele, which results in more 5-HTT. Integrated findings from psychometric evaluations, behavioral animal models, and biological assessments establish a link between the s allele of SLC6A4 and heightened anxiety phenotypes. The allele’s influence on serotonin levels and brain …

Sars-Cov-2 Vaccine Improved Hemostasis Of A Patient With Protein S Deficiency: A Case Report, Mohammad A. Mohammad, Alaa Malik, Lekha Thangada, Diana Polanía-Villanueva, Jovanny Zabaleta, Rinku Majumder

School of Medicine Faculty Publications

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient’s plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent …

Monitoring The Seasonal Presence Of The Blue Shiner, Cyprinella Caerulea, In Little River Canyon National Preserve Using Environmental Dna, Deanna Meadows

Theses

The study of environmental DNA (eDNA) has provided researchers with a more accessible and sensitive way to identify the presence of specific species compared to traditional monitoring methods. eDNA enables species detection by analyzing environmental samples such as water or soil, which contain genetic material shed by organisms in a given area. Research indicates that eDNA techniques have become a valuable method for monitoring threatened and invasive species, proving particularly reliable for detecting aquatic species compared to traditional techniques. Quantitative PCR (qPCR) has been used in numerous eDNA studies, as it provides for greater accuracy than conventional PCR. Cyprinella …

Upregulation Of Fatty Acid Synthase Increases Activity Of Β-Catenin And Expression Of Notum To Enhance Stem-Like Properties Of Colorectal Cancer Cells, Courtney O. Kelson, Josiane Weber Tessmann, Mariah E. Geisen, Daheng He, Chi Wang, Tianyan Gao, B. Mark Evers, Yekaterina Y. Zaytseva

Markey Cancer Center Faculty Publications

Dysregulated fatty acid metabolism is an attractive therapeutic target for colorectal cancer (CRC). We previously reported that fatty acid synthase (FASN), a key enzyme of de novo synthesis, promotes the initiation and progression of CRC. However, the mechanisms of how upregulation of FASN promotes the initiation and progression of CRC are not completely understood. Here, using Apc/VillinCre and ApcMin mouse models, we show that upregulation of FASN is associated with an increase in activity of β-catenin and expression of multiple stem cell markers, including Notum. Genetic and pharmacological downregulation of FASN in mouse adenoma organoids decreases the activation of β-catenin …

Inorganic Pyrophosphate Plasma Levels In Patients With Ggcx-Associated Pxe-Like Phenotypes, Qiaoli Li, Catherine Troutman, Mary Peckiconis, Tamara Wurst, Sharon Terry

Department of Biochemistry and Molecular Biology Faculty Papers

ntroduction: Pseudoxanthoma elasticum (PXE) is an autosomal recessive ectopic calcification disorder clinically affecting the skin, eyes, and vascular system. Most cases of PXE are caused by inactivating pathogenic variants in the ABCC6 gene encoding a hepatic transmembrane efflux transporter, which facilitates the extracellular release of ATP, the precursor of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Pathogenic variants in GGCX, encoding γ-glutamyl carboxylase required for activation of vitamin K-dependent coagulation factors as well as matrix Gla protein (MGP) and Gla-rich protein (GRP), two inhibitors of ectopic calcification, have also been reported to cause cutaneous changes like those seen …

Deciphering Evolutionary Co-Option By Studying The Origin Of Self-Fertility In Caenorhabditis Nematodes, Jonathan P. Harbin

Theses and Dissertations

In my research, I examined the characteristics of male and female sex-determination mutants in C. nigoni and investigated the regulatory pathway they define. This work tested whether flexibility in the sex-determination pathway was a preexisting condition that favored the origin of self-fertility in Caenorhabditis. Furthermore, I developed an approach for using interspecies hybrid mutants to assess the robustness of the C. nigoni pathway. My findings showed that the C. nigoni pathway is highly robust and canalized, suggesting that changes leading to self-fertility must have involved the impairment of this canalization in the germ line, to allow eventual alteration of germ …

Enhanced Bmp Signaling Via Alk2 In Osteoclasts Decreases Bone Density In Mice, Yolanda V. Gutierrez, Hiroyuki Yamaguchi, Yuji Mishina, Yoshihiro Komatsu

Research Colloquium

Bone remodeling is a complex biological process that has been extensively studied. Bone Morphogenetic Proteins (BMPs) are recognized as one of the critical growth factors that coordinate bone remodeling. Previous studies have demonstrated that BMP signaling in osteoclasts has a positive effect on osteoclast function. However, little is known about how each BMP type I receptors control osteoclastogenesis. To investigate this question, we utilized the Cre-LoxP system to specifically activate BMP signaling through ALK2 in mice. We utilized Cathepsin K (Ctsk)-Cre driver to activate BMP signaling in osteoclasts in mice. Compared with aged- and gender-matched controls, gain-of-function of BMP mutant …

Testicular Phenotypes Of Rdhe Dko Mice, Aja Slay

All ETDs from UAB

The bioactive form of vitamin A, all-trans-retinoic acid (RA), plays a critical role in cell differentiation, metabolism, and cellular proliferation by regulating gene transcription. RA signaling is critical during embryogenesis to ensure proper development and during adulthood for tissue maintenance. Disruption of the RA signaling pathway induced by vitamin A deficiency and genetic defects in vitamin A metabolizing enzymes results in embryonic malformations. Previous studies implicate the short-chain dehydrogenase/reductase (SDR) family members as important in RA synthesis. Among the SDR family are retinol dehydrogenase epidermal 2 (RDHE2) and RDHE2-similar (RDHE2S)- collectively RDHE. To gain insight into how RDHE influences the …

Multi-Omics Analysis Of Nf1 Deficiency In Various Cell Types Implicates Roles Outside Of Ras For Cells And Their Microenvironment, Christian Xavier Fay

All ETDs from UAB

Neurofibromatosis type 1 is an autosomal dominant disease in which many patients develop the hallmark feature, neurofibromas, benign tumors that develop along the peripheral nerves. Currently there is no known cure for NF1, and more than 3000 germline pathogenic variants (PVs) in NF1 have been observed. The neurofibromin gene encodes the 320kDa NF1 protein which has multiple predicted functions. Its most under-stood molecular role is in binding GTP-Ras and stimulating Ras-GTPase to cleave GTP to GDP and inactivate Ras signaling. In fact, the only FDA-approved therapeutic is the MEK inhibitor selumetinib which acts downstream of Ras. NF1 also has Ras …

Identifying Links Between Cardiovascular Disease And Insomnia Using Human Genetics And Drosophila Models, Farah Abou Daya

All ETDs from UAB

Cardiovascular disease (CVD) is the leading cause of death worldwide and its in- cidence remains on the rise globally. In addition to other factors, CVD is associated with insomnia, which is the most common sleep disorder. It is defined as the persistent diffi- culty in initiating and/or maintaining sleep. Insomnia symptoms were found to double the risk of incident CVD. However, the specific shared causal pathways remain poorly un- derstood, making it difficult to identify new therapeutic targets that ameliorate insomnia- related CVD risks. Recently, genome-wide association studies (GWAS) identified genet- ic loci significantly associated with insomnia symptoms. Here, we …

Aars Online: A Collaborative Database On The Structure, Function, And Evolution Of The Aminoacyl-Trna Synthetases, Jordan Douglas, Haissi Cui, John J. Perona, Oscar Vargas-Rodriguez, Henna Tyynismaa, Claudia Alvarez Carreño, Jiqiang Ling, Lluís Ribas De Pouplana, Xiang-Lei Yang, Michael Ibba, Hubert Becker, Frédéric Fischer, Marie Sissler, Charles W. Carter Jr., Peter Wills

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like …

Pilbara Demersal Scalefish Resource Recovery Plan 2023- 2043 (Phase 1), Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

The Pilbara Demersal Scalefish Resource (PDSR) includes over 60 demersal scalefish species. The resource is accessed by the Pilbara Trap Managed Fishery, Pilbara Fish Trawl (Interim) Managed Fishery, and the Pilbara Line Fishery (PTMF, PFTIMF & PLF respectively) as well as the recreational and charter fisheries.

The PDSR is managed in accordance with the North Coast Demersal Scalefish Resource Harvest Strategy (Harvest Strategy). The sustainability objectives of the PDSR are set out in the Harvest Strategy and monitored via the use of an indicator species approach, whereby the status of key species is considered representative of the status of the …

Deciphering Cellular Heterogeneity In Spodoptera Frugiperda Midgut Cell Line Through Single Cell Rna Sequencing, Surjeet Kumar Arya, Douglas A. Harrison, Subba R. Palli

Entomology Faculty Publications

Using the 10x Genomics Chromium single-cell RNA sequencing (scRNA-seq) platform, we discovered unexpected heterogeneity in an established cell line developed from the midgut of the Fall armyworm, Spodoptera frugiperda, a major global pest. We analyzed the sequences of 18,794 cells and identified ten unique cellular clusters, including stem cells, enteroblasts, enterocytes and enteroendocrine cells, characterized by the expression of specific marker genes. Additionally, these studies addressed an important knowledge gap by investigating the expression of genes coding for respiratory and midgut membrane insecticide targets classified by the Insecticide Resistance Action Committee. Dual-fluorescence tagging method, fluorescence microscopy and fluorescence- activated cell …

The Influence Of Environmental Change On Genetic Diversity Across Spatial And Taxonomic Scales, Connor M. French

Dissertations, Theses, and Capstone Projects

The spatial distribution of genetic diversity is of interest to biodiversity scientists and conservationists and is a fundamental metric of biodiversity. Genetic diversity patterns across spatial and taxonomic scales contain information about population and assemblage dynamics that can convey their resilience to environmental change. Ectotherms are especially linked to their environments and may be especially sensitive to fluctuations in the environment over time. Herein, I investigate global and regional patterns of genetic diversity in two groups of ectotherms, insects and lizards, to understand the relationship between environmental change and genetic diversity, from populations to assemblages. Overall, my research aims to …

Autophagy And Meiotic Fidelity In C. Elegans, Kaitlin E. Kosinski

Dissertations, Theses, and Capstone Projects

Autophagy is an evolutionarily conserved multi-step recycling process in which cellular material is enclosed in the double membrane-bound autophagosome, which fuses with the lysosome to degrade its contents. Autophagy is essential for development and cellular adaptation to environmental or intracellular stress and is an important regulator of germline stem cell homeostasis in the model nematode C. elegans. We sought to determine if autophagy is important for genome stability during meiosis and found that the core adult C. elegans autophagy genes bec-1, atg-7, unc-51, and atg-18 were all required for proper meiotic development of oocytes. Loss of these …

How Many Fathers? Frequency Of Multiple Paternity In Soupfin Sharks (Galeorhinus Galeus) From California And Australia, Okoiya Kelly

Theses

Multiple paternity has been widely documented in elasmobranch fishes (sharks, rays, and skates); however, the frequency of multiple paternity (FMP; the percentage of sampled litters having multiple sires) varies greatly both among and within species. Understanding the reasons for this inter- and intraspecific variation in FMP may be key to understanding why females mate with multiple males. The soupfin shark (Galeorhinus galeus) is an understudied species in this regard with only one study previously investigating multiple paternity, in which two out of five litters sampled from New Zealand were found to have multiple sires (FMP = 40.0%). We augmented this …

Population Genetic Diversity In Two Biological Systems, Alyson Emery

Electronic Theses and Dissertations

Population genetic analysis can be used to answer questions about population structure and composition in many biological systems. Recent improvements to sequencing technologies have made population genetic studies more accessible than ever before. Many of the same techniques can be applied to different biological systems, but some analyses may differ depending on how genetically divergent the populations in question are. Here, we describe two unique projects using next-generation genome sequencing, each looking at population structure at different levels of genetic divergence: the first involved determining interspecific population structure between two species of hybridizing field cricket using a novel sequencing method, …

Akt Disruption Leads To Non-Canonical Apical Constriction In Drosophila Embryos, Vincent Brown

Electronic Theses and Dissertations

The Akt/mTOR pathway (Akt pathway) has largely been examined in terms of its role as the primary nutrient sensing pathway due to its ability to recognize nutrient availability within a cell, particularly amino acids and glucose. Among its nutrient sensing characteristics, this pathway also contributes to a large variety of other cell functions such as cell growth, proliferation, protein synthesis, and cell survival via anti-apoptotic signaling. Although many aspects of this pathway have been carefully studied, the extent to which it regulates embryonic development remains unclear. Here, I examine Akt function in the early Drosophila embryo and demonstrate that Akt …

Perspectives From Caregivers For Children With Retinoblastoma: Psychosocial Concerns And Genetic Counseling, Kayla Marie Lashinger

Theses and Dissertations

Caregivers play a vital role in the care of children affected with retinoblastoma as most cases are diagnosed before the age of five years old. While previous studies have explored the psychosocial needs of caregivers of children with pediatric cancer, these have not specifically focused on retinoblastoma in the United States (US). Prior research identified the profound emotional burden in terms of depression, anxiety, guilt, isolation, and loneliness experienced by caregivers. Given previous findings and the National Cancer Institute’s recommendation for genetic counseling and testing for all individuals affected with retinoblastoma, this study aimed to assess psychosocial concerns in relation …

The Autistic Adult's Perspective On Genetic Testing In The Prenatal And Cancer Settings, Robin Lisa Urban

Theses and Dissertations

Prenatal and cancer genetic tests are recommended by many professional medical organizations. Previous studies have shown that autistic adults have a negative opinion towards genetic testing for autism but have not explored if this sentiment is shared for other types of genetic testing. We used a descriptive, web-based survey of autistic adults to assess their attitudes towards prenatal and cancer genetic testing (n=36). Our data showed that overall attitudes towards prenatal and cancer genetic testing are positive. Notably, participants had slightly more positive attitudes towards prenatal genetic testing related to neurodevelopmental disorders when compared to testing for disorders primarily affecting …

Assessing Obgyn Residents’ Knowledge, Attitudes, And Current Practices For Carrier Screening, Aubrey Morgan Surian

Theses and Dissertations

Obstetricians and gynecologists (OBGYNs) are the main providers that order carrier screening on a regular basis, so it is important to understand their knowledge, attitudes, and current practices regarding this screening. There are two primary professional organizations that have established practice guidelines for carrier screening, the American College of Obstetrics and Gynecology (ACOG) and American College of Medical Genetics (ACMG). With the growth of pan-ethnic carrier screening, these guidelines have become remarkably different. This study aimed to assess resident OBGYN’s utilization of pan-ethnic carrier screening, discern any discrepancies between knowledge, attitudes, and current practices, identify possible practice resources that may …

Perception Of Alzheimer’S Actionability Among End Users Of Direct-To-Consumer Genetic Tests, Emily Mason

Theses and Dissertations

The APOE ε4 allele is the best-known genetic risk factor for developing late-onset Alzheimer’s disease. Although new evidence is emerging, the extent to which lifestyle improvements can reduce Alzheimer’s risk needs further investigation. Research suggests that individuals with a higher genetic risk may be more likely to engage in risk-reducing health behavior changes following results disclosure. This study aimed to better understand these findings by assessing the health behavior and perceptions of Alzheimer’s actionability among consumers of DTC genetic tests. Our study revealed that individuals with 2 copies of the APOE ε4 allele were less likely to make lifestyle modifications …

Patients’ Experience Of Care Following Perinatal Case Conference, Mary Elise Nolen

Theses and Dissertations

The Perinatal Case Conference (PCC) at Prisma Health-Midlands Maternal-Fetal Medicine (MFM) is a biweekly multidisciplinary meeting to discuss pregnancies with prenatally identified congenital anomalies. Patients are primarily cared for by MFM and may have appointments with various subspecialists during their pregnancy. The goals of the PCC are multidisciplinary collaboration in planning for the management of each pregnancy and familiarizing each practitioner with the pending cases, so if or when intervention is needed, the clinicians are familiar with the case.

Researchers performed a chart review and surveyed patients whose pregnancies were discussed in the PCC to learn the patient’s perspective of …

The Utility Of Referrals From A State Early Intervention System To A Pediatric Genetics Clinic To Increase Access To Genetic Services, Mikayla Jennings

Theses and Dissertations

Infants or toddlers enrolled in state early intervention programs have developmental delays or are diagnosed with conditions that may result in developmental delays. These infants receive a wide range of services from early intervention. In the state of South Carolina, children in the early intervention program are offered genetic evaluations at no cost to the family. Exploring the relationship between state early intervention systems and genetic clinics and the impact on this particular patient population can provide support for new and continued use of this service delivery model.

The purpose of this study was to evaluate the service delivery model …