Digital Commons Network^™

Investigating The Thermodynamic Properties Of Fat10 And Fat10ylated Proteins, Aravind R

Theses and Dissertations

Degradation of proteins by the proteasome is crucial in regulating protein levels in the cell. Post-translational modifications, such as ubiquitylation and Fat10ylation, trigger proteasomal degradation of the substrate proteins. While ubiquitylation orchestrates multiple cellular processes, Fat10ylation is primarily involved in the inflammatory response. Unlike ubiquitin, recycled upon substrate degradation, Fat10 is degraded along with its substrate. Although the thermodynamic properties of the substrate are critical for effective proteasomal degradation, they remain poorly understood for the Fat10-proteasome pathway.

Here, we demonstrate that Fat10 exhibits markedly lower thermodynamic stability and faster unfolding kinetics compared to ubiquitin. This is due to the absence …

Role Of Ring-Box E3 Ligases In Runx2 And Sp7 Protein Turnover During Osteoblast Differentiation, Abeera Sikandar

All ETDs from UAB

The bone matrix synthesis by osteoblast during skeletogenesis is regulated by several transcription factors and signaling pathways. Runx2 and Sp7 are master regulators of osteoblast differentiation and bone formation. Deletion of both genes in mice results in the complete failure of ossification. In humans, Sp7 and Runx2 genes mutations cause osteogenesis imperfecta and cleidocranial dysplasia, respectively. The progression of osteoblast differentiation requires a coordinated and temporal expression of Runx2 and Sp7 genes. Posttranslational modifications regulate the cellular levels and function of Runx2 and Sp7 proteins. Ubiquitination controls protein turnover through targeted degradation. The multi-subunit SCF-complex is the largest class of …

Crisprofft: Comprehensive Database Of Crispr/Cas Off-Targets, Grant Wang, Xiaona Liu, Aoqi Wang, Jianguo Wen, Pora Kim, Qianqian Song, Xiaona Liu, Xiaobo Zhou

Faculty, Staff and Student Publications

The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) programmable nuclease system continues to evolve, with in vivo therapeutic gene editing increasingly applied in clinical settings. However, off-target effects remain a significant challenge, hindering its broader clinical application. To enhance the development of gene-editing therapies and the accuracy of prediction algorithms, we developed CRISPRoffT (https://ccsm.uth.edu/CRISPRoffT/). Users can access a comprehensive repository of off-target regions predicted and validated by a diverse range of technologies across various cell lines, Cas enzyme variants, engineered sgRNAs (single guide RNAs) and CRISPR editing systems. CRISPRoffT integrates results of off-target analysis from 74 studies, encompassing …

Information Technology Management And Emotional Intelligence, Tina M. Muheim

Walden Dissertations and Doctoral Studies

Information technology (IT) employees often face high stress, burnout, and turnover, indicating a potential gap in IT leaders’ emotional intelligence (EI), which may hinder their ability to support and retain their teams effectively. Since IT plays a critical role in organizational performance and achieving strategic goals, addressing this gap is crucial for improving team well-being and organizational success. Grounded in EI theory, the purpose of this quantitative correlational study was to examine the relationship between IT managers’ EI subscales—assertiveness and interpersonal relationships—and their influence on the EI subscale, happiness/well–being indicator. The participants were 38 IT managers from U.S. organizations who …

The Manipulation Of Odor Availability Of Training Aids Used In Detection Canine Training, Katylynn B. Sloan, Michele N. Maughan, Caitlin E. Sharpes, Robin R. Greubel, Shawna F. Gallegos, Aleksandr E. Miklos, Lindsay D. Waldrop

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Detection canines can identify numerous substances for which they have been trained. Historically, and a point of ongoing contention, detection canine threshold (i.e., sensitivity or limit of detection) training has primarily focused on changing the weight of the training aid substance used. There has been minimal focus on other principles, such as surface area, confinement, and temperature, which can be manipulated to affect odor availability. That said, trainers have been manipulating odor availability for years without necessarily understanding the governing scientific principles. The aim of this review is to highlight the principles that control odor availability of a substance and …

Selectivity Of Invasive Species Suppression Efforts Influences Control Efficacy, Rae Fadlovich, Kevin Landom, Timothy E. Walsworth

Watershed Sciences Student Research

1. Highly fecund invaders and size-selective suppression efforts often limit the effectiveness of invasive species control programs, as compensatory processes can allow suppressed populations to recover. While population models have long explored how demographic characteristics impact management feasibility, there is a growing need to evaluate how the selectivity of suppression efforts might impact the long-term feasibility of control.
2. We use a simulation framework that integrates age-based selectivity to evaluate the effect of increasing the range of ages selected for during harvest-based invasive species control. We applied this approach to common carp in Utah Lake, the location of one of the world's …

Alternative Splicing In The Brain: Across Disease States, Sexes, Regions, And Cell Types, Emma Finn Jones

All ETDs from UAB

Molecular phenotype heterogeneity is prevalent across multiple contexts and is mediated by mRNA expression differences and the gene and isoform level. Isoform-level mRNA complexity in the brain is essential for healthy neurodevelopment, and perturbations in AS are associated with many neurological and psychiatric disorders. While previous research has examined how AS changes in the brain, there is still a gap in using newer techniques to study these changes with greater specificity. Therefore, we address this gap by using long-read and scRNA-seq technologies to study isoform-level diversity in AS across four contexts (i.e., disease, sex, region, and cell type) in the …

Single Nucleus Multiomics Reveals The Drought-Driven Gene Regulatory Atlas In Arabidopsis, Jinbao Liu

All ETDs from UAB

The regulation of gene expression in plant responses to drought has been thoroughly in-vestigated in previous studies. Despite this, a detailed understanding of the cell type-specific regulatory mechanisms, encompassing multi-layered biological processes, is lack-ing. In this study, we report the use of single nucleus multiomic analysis in Arabidopsis seedlings in response to drought stress. Our single-nuclei RNA (snRNA) analysis deline-ated 14 distinct clusters representing major root and shoot cell types and discovered new cell type-specific drought markers. Integration of snRNA with single-nuclei ATAC (snATAC) data in leaf epidermis, root endodermis, and guard cells revealed accessible chromatin regions (ACRs)-linked genes predominantly …

Controlled By Disorder: Modifications To An Unstructured C-Terminal Region Alter Srsf1'S Intramolecular Interactions And Tendency To Phase Separate, Talia Fargason

All ETDs from UAB

The protein Serine-Arginine-rich Splicing Factor 1 (SRSF1) is essential in multiple stages of the mRNA lifecycle, including alternative splicing, nonsense-mediated decay, and nuclear export. SRSF1’s dysfunction is linked to cancers, viral evasion, and developmental disorders. Its function depends on interactions between structured and unstructured regions, modulated by phosphorylation. However, the unstructured regions, while critical for regulation, contribute to protein insolubility, hindering full-length studies. Prior to the work presented here, structural studies of SRSF1 were limited to analysis of its isolated domains. This dissertation develops new techniques to characterize SRSF1, focusing on its intermolecular interactions driving phase separation and intramolecular interactions …

Elucidating The Impact Of Ribosome Biogenesis On Breast Cancer, Amr Rafat Elhamamsy

All ETDs from UAB

Ribosome biogenesis, a complex and multi-step process that occurs predominantly in the nucleolus, plays a critical role in cellular function by mediating protein synthesis through the assembly of ribosomal RNAs (rRNAs) and ribosomal proteins into functional ribosomes. In cancer, dysregulation of this process is linked to the development of specialized ribosomes (onco-ribosomes) that support oncogenic translation programs, enhancing tumor progression and therapeutic resistance. This dissertation explores the interplay between ribosome biogenesis and cancer, focusing particularly on the role of RNA Polymerase I (RNA Pol I) activity under hypoxic conditions and rRNA modifications in breast cancer. My first study elucidates the …

Production And Radiochemistry Of Theranostic Radioscandium Nuclides, Shelbie Jaylene Cingoranelli

All ETDs from UAB

In nuclear medicine, theranostics utilizes radionuclide pairs for diagnosis and therapy. Radioscandium isotopes (43Sc, 44Sc, and 47Sc) offer a promising alternative to the 68Ga/177Lu theranostic pair due to their identical radiolabeling conditions, complexes and in vivo pharmacokinetics. 43Sc (t1/2=3.89h, β+=88%) and 44Sc (t1/2 =3.97h. β+=94.3%) are suitable for Positron Emission Tomography (PET) imaging whereas 47Sc (t1/2=3.3d. Eβ-ave=162keV) is suitable for targeted radiotherapy and Single Photon Emission Computed Tomography (SPECT). These isotopes require production routes that lead to high radionuclidic purity and radiochemistry development for incorporation into radiopharmaceuticals. This study explores the production, purification, and application of these isotopes. The proton …

Cytotoxic, Genotoxic, And Metabolic Effects Of Dihydroxyacetone In Heart, Liver And Lung Models, Arlet Hernandez

All ETDs from UAB

Dihydroxyacetone (DHA) is a triose sugar found as an active ingredient in sunless tanning products (STPs) and by-product in electronic cigarettes (e-cigarettes). DHA can rapidly be absorbed into cells and tissues and incorporated into several metabolic pathways through its conversion into dihydroxyacetone phosphate (DHAP). Previous studies have shown that DHA promotes cytotoxicity and genotoxicity primarily characterized in skin models. The extent of these effects in systemic models is highly cell-type specific. Here we investigate the cytotoxic, genotoxic, and metabolic effects of DHA across several cell models. First, we investigated the effects of DHA in a metabolically active cell line, hepatocellular …

Vitamin D Receptor Signaling Antagonizes RorT Signaling To Reprogram Th17 Cells, Blake Frey

All ETDs from UAB

Vitamin D3 has long been associated with protection against a myriad of autoimmune diseases commonly linked to dysregulation of the T helper 17 (Th17) program. Th17 cells rely on the nuclear receptor (NR) RORγt as the master transcription factor for differentiation and function, establishing a metastate that can drive pro-inflammatory or alternative pathways depending on external cues. Vitamin D3 signals through another NR, the vitamin D receptor (VDR), to inhibit IL-17A in favor of the immunosuppressive cytokine IL-10; however, the precise mechanisms remain unclear. We developed a novel dual Vdr reporter and conditional knockout mouse model, and for the first …

The Evolutionary Ecology Of Reproductive System Variation In Haploid-Diploid Freshwater Red Macroalgae, Sarah Connelly

All ETDs from UAB

Reproductive systems describe the relative rates of sexual versus asexual reproduction and selfing versus outcrossing, governing the transmission of genetic diversity between generations and shaping evolutionary responses to environmental change. Though sex has inherent costs, it contributes to the reproductive system for most eukaryotes, generating incredible life cycle diversity. Life cycles are expected to be correlated with different reproductive systems. Diploid life cycles should be associated with outcrossing, whereas life cycles with a long-lived haploid phase are hypothesized to be associated with selfing and asexual reproduction. To test this hypothesis, we used ten polymorphic microsatellite loci to genotype 311 gametophytes …

Targeted Exon Skipping Of Nf1 Exon 52 As A Mutation Specific Therapeutic For Neurofibromatosis Type 1, Cameron Lee Church

All ETDs from UAB

Modification of pre-mRNA splicing using antisense oligonucleotides (ASOs) can be used to skip one or more exons carrying pathogenic DNA sequence variants. Our previ-ously published data indicates NF1 exon 52 is a good target for exon skipping as a cDNA screen indicates an NF1 isoform lacking exon 52 maintains both high neurofi-bromin expression and the ability to suppress Ras activity. To develop an exon skipping approach, we designed antisense phosphorodiamidate morpholino oligomers (PMOs) to skip exon 52. Our lead PMO has a low IC50 of 45nM and is able to restore NF1 expres-sion and Ras-suppression in a cell line with …

Scalable Resonance-Based Multi-Coil Inductive Links For Wireless Power Transmission And Passive Sensing In Biomedical Applications, Reepa Saha

All ETDs from UAB

Type 2 Diabetes (T2D) has become a major health crisis, affecting up to 95% of the 38.4 million diabetes cases in the United States and costing approximately $327 billion annually. Current treatments mainly focus on symptom management rather than reversing the disease. However, clinical observations suggest a promising link between certain stomach surgeries, such as the removal of the upper stomach, and diabetes reversal within a year. This raises the possibility of anatomical changes influencing diabetes outcomes, though the underlying neural mechanisms remain unclear. This dissertation is organized into three interconnected research segments, each contributing to a platform that deepens …

Diurnal Function And Expression Of Aquaporins In The Mouse Kidney, Phi Hung Nguyen

All ETDs from UAB

Aquaporins (AQPs) are a family of proteins that play a major role in maintaining water homeostasis. Aquaporin 2 (AQP2) and aquaporin 3 (AQP3) are expressed in the collecting duct and regulated by the antidiuretic hormone arginine vasopressin (AVP) through the AVPR2 receptor. It is well known that biological circadian rhythms are critical for maintaining homeostasis. In both humans and rodents, the kidneys exhibit time-of-day-dependent changes in function. We hypothesized that there is a diurnal pattern in urine and/or plasma osmolality, and that this may reflect changes in kidney aquaporins in mice. Male and female C57BL/6J mice (10-11 weeks old) were …

Increasing The Knowledge, Awareness, And Readiness To Change Of Cultural Sensitivity Among Public Health College Students, Margaret Enlow

All ETDs from UAB

This research examined if a lecture-based intervention increased the DEI knowledge, awareness, and readiness to change in undergraduate public health students. Topics included a systematic review of DEI activities in undergraduate public health classrooms/academic programs, determining reliability of an adapted tool to measure knowledge, awareness, and readiness to change, and statistical analyses of pre- and post-data to determine knowledge, awareness, and readiness to change after students participated in the lecture-based intervention. The systematic review identified a gap in the literature regarding public health DEI education in the classroom. Through additional analyses, themes of DEI were identified in previous publications that …

Point-Of-Care Portable Perfusion Phantom For Accurate Dce-Mri Measurement, Martin Dawson Holland

All ETDs from UAB

Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) monitors the temporal changes in contrast agent concentration within human tissues to assess the pharmacokinetic parameters of that tissue. Traditionally, these scans are evaluated qualitatively, but quantitative DCE-MRI (qDCE) may improve patient care by enabling more objective and accurate data analysis. One significant challenge hindering the broader adoption of qDCE is the variability of data across different MRI machines. Each manufacturer employs unique hardware and software configurations, leading to inconsistencies in quantifying the contrast agent concentration in tissues and, consequently, the pharmacokinetic parameters. Even using the same scanner, measurements can drift due to hardware …

Social Dominance And Cortical Neuronal Synchrony In Male Mecp2 Knockout Mice, Cesar Andres Acevedo Triana

All ETDs from UAB

Social behaviors are critical for the survival of individuals, and their dysfunction is common in several neuropsychiatric and neurodevelopmental disorders including autism, where impaired sociability is one of the core diagnostic symptoms and compromises the interpretation of social cues, with an apparent lack of interest in others. Among the neurodevel opmental disorders associated with autism, Rett syndrome (RTT) is a disorder predominantly affecting females and caused by spontaneous loss-of-function mutations in the X-linked MECP2 gene, which encodes the transcriptional regulator MeCP2 that regulates many critical genes. RTT individuals have impaired motor, cognitive, and social abilities most of which are recapitulated …

Metabolic And Physiological Characteristics Of Diet Manipulation And Genetic Modification In Two Rat Models Of Aging, Soe Maung Maung Phone Myint

All ETDs from UAB

As society and human civilization advances, humans have begun to live longer and most people live to be longer than 60, which was not the case several decades ago. According to the World Health Organization(WHO), by the turn of the next decade at 2030, 1 in 6 people will be 60 years or older, accounting for almost 1.4 billion people. Aging affects people differently but in general, it has a propensity to induce widespread and progressive molecular and cellular damage which leads to a myriad of diseases and eventually death. The greatest risk factor for most of the chronic diseases …

The Relationship Between Molten Iron Chemistry Of A Cupola Furnace And Airborne Contaminants, Darkeya D. Rowe

All ETDs from UAB

The purpose of this research was to understand the potential relationship between the molten iron chemistry of a cupola furnace and airborne contaminants. Three-day air sampling was performed for the emissions of a cupola furnace using 37 mm mixed cellulose ester (MCE) filter cassettes at an iron foundry. The samples were analyzed for 21 elements and compounds by a commercial laboratory using the modified National Institude for Occupational Safety and Health (NIOSH) Method 7303, most of which were metals. The concentrations of 13 out of 21 elements and compounds were compared to the corresponding elements in molten metal/iron stream analyzed …

Effects Of Whole-Food, Plant-Centered Diets On Glycemic Control, Medication Use, Ectopic Fat, And Cardiovascular Health In Adults With Type 2 Diabetes, Cody Hanick

All ETDs from UAB

Type 2 diabetes (T2D) is a global health and economic concern. Safe and effective treatments for T2D, including dietary approaches, are limited. Additionally, it remains unclear whether dietary carbohydrate quality or quantity matters more for managing T2D. Most nutrient-dense carbohydrate quality sources—such as fruit, vegetables, legumes, and whole grains—come from plant foods and are recommended for people with T2D by the American Diabetes Association. Furthermore, when these food groups are combined into a dietary pattern, a whole-food, plant-based (WFPB) diet is created. However, few studies have tested the effects of a WFPB diet or carbohydrate-rich food groups in people with …

Information Technology Management And Emotional Intelligence, Tina M. Muheim

Walden Dissertations and Doctoral Studies

Information technology (IT) employees often face high stress, burnout, and turnover, indicating a potential gap in IT leaders’ emotional intelligence (EI), which may hinder their ability to support and retain their teams effectively. Since IT plays a critical role in organizational performance and achieving strategic goals, addressing this gap is crucial for improving team well-being and organizational success. Grounded in EI theory, the purpose of this quantitative correlational study was to examine the relationship between IT managers’ EI subscales—assertiveness and interpersonal relationships—and their influence on the EI subscale, happiness/well–being indicator. The participants were 38 IT managers from U.S. organizations who …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

Faculty, Staff and Student Publications

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Circakb: A Comprehensive Knowledgebase Of Circadian Genes Across Multiple Species, Xingchen Zhu, Xiao Han, Zhijin Li, Xiaobo Zhou, Seung-Hee Yoo, Zheng Chen, Zhiwei Ji

Faculty, Staff and Student Publications

Circadian rhythms, which are the natural cycles that dictate various physiological processes over a 24-h period, have been increasingly recognized as important in the management and treatment of various human diseases. However, the lack of sufficient data and reliable analysis methods have been a major obstacle to understanding the bidirectional interaction between circadian variation and human health. We have developed CircaKB, a comprehensive knowledgebase of circadian genes across multiple species. CircaKB is the first knowledgebase that provides systematic annotations of the oscillatory patterns of gene expression at a genome-wide level for 15 representative species. Currently, CircaKB contains 226 time-course transcriptome …

Perspectiva De Género En La Animación: Desafíos Y Logros En La Industria, Carmen Pérez González, Luis Mayo Vega

GDI. Revista de investigación de Género, Diseño e Innovación

La perspectiva de género en la industria de la animación se centra en los desafíos y logros que enfrentan las mujeres en este campo. Se identifican los principales obstáculos que afrontan las directoras de animación, evidenciando un aumento en la representación femenina a lo largo de los años, aunque aún lejos de alcanzar la igualdad. Se destaca la importancia de incluir voces femeninas en la investigación académica para promover una representación equitativa. La metodología analiza informes recientes que evalúan la participación de mujeres en la industria y se recopilan recomendaciones de directoras destacadas para fomentar la equidad de género. Los …

Monitoring And Assessment Of Population, Reproductive, And Health Effects In Colonial Waterbirds Breeding At Contaminated Great Lakes Sites In Michigan, Keith A. Grasman, Mandy Annis, Carly Eakin, Jeremy Moore, Lisa L. Williams

University Faculty Publications and Creative Works

Immunological, reproductive, and population endpoints were assessed in fish-eating birds during 2010–2019 in the Saginaw River and Bay and River Raisin Areas of Concern (AOCs) and Grand Traverse Bay, which are ecosystems historically contaminated with polychlorinated biphenyls, dibenzo-p-dioxins, and dibenzofurans. Reference sites were in the lower St. Marys River (herring gulls and Caspian terns), eastern Lake Superior (terns), and eastern Lake Huron (black-crowned night herons). Relative risk ratios for embryonic nonviability (from both infertility and mortality) in gull embryos were 2–3-fold higher than the reference site in both AOCs and Grand Traverse Bay. Twelve of 13 deformed embryos and chicks …

Intrinsic Adaptive Plasticity In Mouse And Human Sensory Neurons, Lisa A Mcilvried, John Smith Del Rosario, Melanie Y Pullen, Andi Wangzhou, Tayler D Sheahan, Andrew J Shepherd, Richard A Slivicki, John A Lemen, Theodore J Price, Bryan A Copits, Robert W Gereau

2020-Current year OA Pubs

In response to changes in activity induced by environmental cues, neurons in the central nervous system undergo homeostatic plasticity to sustain overall network function during abrupt changes in synaptic strengths. Homeostatic plasticity involves changes in synaptic scaling and regulation of intrinsic excitability. Increases in spontaneous firing and excitability of sensory neurons are evident in some forms of chronic pain in animal models and human patients. However, whether mechanisms of homeostatic plasticity are engaged in sensory neurons of the peripheral nervous system (PNS) is unknown. Here, we show that sustained depolarization (induced by 24-h incubation in 30 mM KCl) induces compensatory …

Distinct Properties And Activation Of Hexameric And Heptameric Pannexin 1 Channel Concatemers, Smriti Gupta, Yu-Hsin Chiu, Mohan C Manjegowda, Bimal N Desai, Kodi S Ravichandran, Douglas A Bayliss

2020-Current year OA Pubs

Pannexin 1 (PANX1) is a member of a topologically related and stoichiometrically diverse family of large pore membrane ion channels that support the flux of signaling metabolites (e.g., ATP) and fluorescent dyes. High-resolution structural analyses have identified PANX1 as a heptamer despite early evidence suggesting that it might be a hexamer. To determine if PANX1 channel activity is supported in both hexameric and heptameric conformations, we examined properties of concatenated PANX1 constructs comprising either six or seven subunits with intact or truncated C-termini (the latter to mimic caspase-cleavage activation). In whole-cell recordings from PANX1-deleted cells, the C-tail-truncated hexameric and heptameric …