Life Sciences Commons^™

Acclimation, Long-Term Repeatability, And Phenotypic Correlations Of Aerobic Metabolic Traits In The Gulf Killifish, Fundulus Grandis, Jessica E. Reemeyer

University of New Orleans Theses and Dissertations

This research examined the effects of acclimation to lowered salinity, elevated temperature, and hypoxia on aerobic metabolism of the Gulf killifish, Fundulus grandis, a common estuarine resident of the Gulf of Mexico. Standard metabolic rate (SMR), maximum metabolic rate (MMR), absolute aerobic scope (AAS), and critical oxygen tension (P_crit) were each influenced by one or more acclimation treatments. Assessing the consistency of these traits measured in the same individuals over time, all were found to be significantly repeatable with no indication that the repeatability of any traits was affected by acclimation conditions. Significant correlations were found between …

Molecular Insights Into Major Peripheral T-Cell Lymphoma Entities With Advances In A Representative Model System, Tayla B. Heavican

Theses & Dissertations

Peripheral T-cell lymphoma (PTCL) is a group of complex clinicopathological entities associated with an aggressive clinical course. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-not otherwise specified (PTCL-NOS) are the two most frequent categories accounting for more than 50% of PTCLs. Gene expression profiling (GEP) defined molecular signatures for AITL and delineated biological and prognostic subgroups within PTCL-NOS (PTCL-GATA3 and PTCL-TBX21). Genomic copy number analysis and targeted sequencing revealed unique genomic abnormalities and oncogenic pathways, indicating distinct oncogenic evolution. PTCL-GATA3 exhibited higher genomic complexity characterized by frequent loss or mutation of tumor suppressor genes targeting the CDKN2A/B-TP53 axis and PTEN-PI3K pathways. …

Brca1 & Ctdp1 Brct Domainomics In The Dna Damage Response, Kimiko L. Krieger

Theses & Dissertations

Genomic instability is one of the enabling characteristics of cancer. DNA damage response pathways are important for genomic integrity and cell cycle progression. Defects in DNA damage repair can often lead to cell cycle arrest, cell death, or tumorigenesis. The activation of the DNA damage response includes tightly regulated signaling cascades that involve kinase phosphorylation and modular domains that scaffold phosphorylated motifs to coordinate recruitment of DNA repair proteins. Modular domains are conserved tertiary structures of a protein that can fold, function, and evolve independently from an intact protein. One of the most common modular domains involved in DNA damage …

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

Functional Implications Of Nlrp1 Variants For Autoimmune Disease, Laura J. Westhoff

Undergraduate Honors Theses

NLRP1 is a protein-coding human gene that plays a crucial role in the NLRP1 inflammasome. Variants to the NLRP1 gene have been associated with autoimmune and autoinflammatory diseases. We examined the effects of polymorphisms at two SNPs on cytokine levels and NLRP1 gene expression in 50 human volunteers without diagnosed autoimmune disease. NLRP1 was genotyped at SNPs rs2670660 and rs12150220 and individuals who were homozygous at one or more SNP were selected for further analysis. Serum IL-18 and IL-1β levels were quantified using ELISA. NLRP1 gene expression was measured using real-time PCR. A strong linkage was found between genotypes of …

Characterizing The Combination Of Rpa Inhibitors With Parp Inhibitors In High-Grade Serous Ovarian Cancer, Yat Tang

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) is the most common and deadly gynecologic malignancy. HGSC patients with BRCA1/2 mutations have homologous recombination deficiency (HRD), requiring parallel pathways to maintain genome integrity (e.g., PARP1, PARP2). Approximately 50% of ovarian carcinomas are estimated to exhibit HRD. For the remaining 50% and the large percentage of HRD patients with acquired or innate resistance to single-agent PARP inhibitors, there is a need to develop alternative therapeutic strategies.

Replication Protein A (RPA) is a heterotrimeric protein crucial for genome maintenance. Phosphorylation of RPA in DNA damage response (DDR) is a negative regulator of DNA end resection. …

Ecdysoneless, A Novel Regulator Of Ca2+ Homeostasis And Metabolism, Aniruddha Sarkar

Theses & Dissertations

The hallmarks of cancer include sustained proliferation and survival in the face of cellular stresses imposed by the oncogenic drive, as well as metabolic rewiring for tumor growth under adverse nutritional conditions. Adaptive alterations in key biochemical networks that underlie metabolic rewiring represent potential opportunities to develop new therapeutic strategies against cancer.

My thesis focuses on mammalian Ecdysoneless (ECD), a conserved homolog of the fly Ecdysoneless gene product, which engages fundamental cell biological processes of ER stress, Ca²⁺ signaling and metabolism to help sustain the oncogenic drive in tumor cells. Recent studies from our laboratory provide a clear evidence …

Acid Resistance Mechanisms In Staphylococcus Aureus, Chunyi Zhou

Theses & Dissertations

Staphylococcus aureus is a leading cause of opportunistic infections in community and health care settings. To thrive in a great variety of environments, S. aureus has developed the capability of tolerating temporary pH changes, as well as resisting constant acid stress. To evaluate the impact of strong and weak acid stress on S. aureus, growth patterns of JE2 were monitored when cultured in chemically defined media (CDM) at various pH in the presence of hydrochloric acid (HCl), acetic acid, and lactic acid. Our results showed that S. aureus responds to strong and weak acids in different manners. S. aureus …

The Role Of Reactive Oxygen Species In Regulating Macrophage And Fibroblast Activation Within The Breast Cancer Tumor Microenvironment, Brandon J. Griess

Theses & Dissertations

The tumor microenvironment (TME) is a key determining factor in breast cancer, especially the more aggressive subtype triple negative breast cancer (TNBC). The activated fibroblasts and macrophages within the TME have many tumor promoting functions. Therefore, targeting their activation presents a novel therapeutic approach in TNBC. My work studied the role of reactive oxygen species (ROS) during fibroblast and macrophage activation in breast cancer.

My studies showed that expression of the secreted antioxidant enzyme, EcSOD, is silenced in breast cancer samples, in part, via increased promoter methylation. The re-expression of EcSOD inhibited c-Met activation in the TNBC cell line, MDA-MB231. …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

Mechanism Of Bax/Bak Activation In Apoptotic Signaling, Kai Huang

Theses & Dissertations

The Bcl-2 family proteins, including the anti-apoptotic members, pro-apoptotic effectors Bax/Bak, and the BH3-only proteins, are key components of the mitochondrial apoptotic pathway. The BH3-only protein Bid is critical for the mitochondrial pathway of apoptosis after TRAIL-induced death receptor activation. However, the mechanism of Bid activation during TRAIL-induced apoptosis is unclear. By putting back wild-type and mutants of Bid in Bid deficient (Bid KO) and Bid/Bax/Bak TKO colon cancer cells, we demonstrated that cleavage by caspase 8 and mitochondrial targeting are critical events for Bid activation. One of the biggest mysteries in apoptosis is how Bax/Bak was activated by BH3-only …

Hdac1 Is A Required Cofactor Of Cbfβ-Smmhc And A Therapeutic Target In Inversion 16 Acute Myeloid Leukemia, Lisa E. Richter

Theses & Dissertations

Acute myeloid leukemia (AML) is a neoplastic disease characterized by the uncontrolled proliferation and accumulation of immature myeloid cells. A common mutation in AML is the inversion of chromosome 16 [inv(16)], which generates a fusion between the genes for core binding factor beta (CBFB) and smooth muscle myosin heavy chain (MYH11), forming the oncogene CBFB-MYH11. The expressed protein, CBFβ-SMMHC, forms a heterodimer with the key hematopoietic transcription factor RUNX1. Although CBFβ-SMMHC was previously thought to dominantly repress RUNX1, recent work suggests that CBFβ-SMMHC functions together with RUNX1 to activate transcription of specific target genes.

Targeting the …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …

Defining The Role Of Tyrosine Phosphorylation In The Regulation Of Connexin43 In Cardiac Diseases, Li Zheng

Theses & Dissertations

Connexins are integral membrane proteins that oligomerize to form gap junction channels. Ions and small molecules diffuse intercellularly through these channels, allowing individual cellular events to synchronize into the functional response of an entire organ. Gap junction channels composed of Connexin43 (Cx43) mediate electrical coupling and impulse propagation in the normal working myocardium. In the failing heart, Cx43 remodeling (decreased expression, altered phosphorylation state, loss at intercalated discs, and increased presence at lateral membranes) contributes to rhythm disturbances and contractile dysfunction. While there is considerable information regarding key interactions of Cx43 in the regulation of gap junction channels, unfortunately, the …

Microfiber Concentrations In Sand From Nesting Sea Turtle Beaches In Costa Rica, South Carolina, And Florida., Kaylin Leroy, George Boneillo

Honors Theses

Microplastics are an increasing threat to marine environments and the organisms that inhabit them. Since plastic pollution in the ocean is prominent throughout the globe, microplastic is washing ashore, affecting important sea turtle nesting sites. This study quantified microfibers in the sand of various sea turtle nesting sites around the world. Sand samples were collected in Myrtle Beach (South Carolina), Destin (Florida) and the Pacuare Reserve (Costa Rica). The microfibers were retrieved using a super saline solution and then filtered under a hood. Filters were then counted using microscopy. Microfibers were found at every sampling site, with the lowest surface …

Potential Arm Preference Within Starfish Species Including Asterias Vulgaris And Luidia Clathrata: A Study And Summary, Rebecca Jones, Young Robert

Honors Theses

Foraging arm preference was tested in two species of starfish: Asterias vulgaris and Luidia clathrata. No evidence was found for a species-wide preference or for a preference by individual sea stars, but trials were impacted by illness and resulting low sample size.

Predation Effects On Mid-Marsh Ribbed Mussel Mortality, Cluster Size, And Facilitation Of Cordgrass Growth, Colten Winter, Keith Walters

Honors Theses

Reciprocal facilitation between Geukensia demissa, ribbed mussels, and Sporobolus alterniflorus, cordgrass, has a positive effect on salt marsh ecosystems. Mussel clusters enhance cordgrass growth and drought resistance and cordgrass provides attachment and shade for mussel aggregations. Along with benefits for both mussels and cordgrass, the mutualism facilitates increased biodiversity and shoreline stabilization and enhances marsh ecosystem functions. Aspects of mussel patch configuration including cluster size, perimeter and connectivity modulate the reciprocal facilitation effects of cordgrass and mussels on marsh ecosystems. In a northern South Carolina marsh system, mussel patch configuration positively influenced cordgrass biomass. Predation affected mussel patch …

Effects Of Temperature On Enzyme Activity Of Aquatic Litter-Associated Fungi, Nicholas Bautz

Honors Theses

The decomposition of leaf litter in aquatic ecosystems is carried out mostly by microorganisms, including bacteria and fungi. Fungi, known as aquatic hyphomycetes, dominate microbial communities in the decomposition of leaf litter. These fungi produce extracellular enzymes that aid in the sequestration of carbon and nutrients and lead to the breakdown of complex plant polymers. We evaluated the effects of temperature on extracellular enzyme activity within the framework of the Metabolic Theory of Ecology (MTE). The activity of β-1,4-glucosidase and β-1,4-xylosidase was estimated fluorometrically using artificial substrate analogs. Phenol oxidase activity was estimated spectrophotometrically from oxidation of L-DOPA (L-3,4-dihydroxyphenylalanine). We …

A Landscape On The Threshold Of Change: Patterns Of Soil Microbial Ecology Along Dynamic Geomorphic And Hydrologic Features In A Polar Desert, Kelli L. Feeser, David J. Van Horn, Heather N. Buelow, Daniel R. Colman, Theresa A. Mchugh, Jordan G. Okie, Egbert Schwartz, Cristina D. Takacs-Vesbach, Becky A. Ball, Andrew G. Fountain, Michael N. Gooseff, Joseph S. Levy, Maciej K. Obryk

Biology ETDs

The McMurdo Dry Valleys (MDV) of Antarctica are on the threshold of widespread landscape scale change due to increasing temperature and solar radiation and altered hydrology: buried ice is melting, the soil active layer is thickening, thermokarst features are developing along streams, water tracks are expanding, and lake levels are rising. These changes will impact the microbial communities found in each of the affected habitats. The purpose of this work is to first, understand the spatial distribution of soil bacteria in the MDV, specifically investigating the scale-dependent effects of environmental heterogeneity, and second, to perform surveys and coupled experiments to …

Trade-Offs Between Survival And Reproduction In Starvation-Selected Drosophila Melanogaster, Tammara Beeghly

UNLV Theses, Dissertations, Professional Papers, and Capstones

Evolutionary outcomes are demonstrated by traits that affect an organism’s schedule of reproduction and survival. These life history traits are reflected in an organism’s physiology, development and behavior. Environmental changes, such as availability of nutritional resources, can profoundly affect evolutionary outcomes of individuals and populations. When shortages arise, there will be trade-offs in the allocation of resources, where one trait prevails at the expense of another.

In the laboratory, we can mimic conditions in nature and study the specific effects of the conditions that we re-create. In our case, over 100 generations of Drosophila melanogaster have been selected for starvation …

Uncovering New Mechanisms Of Cdc34 And Cullin-Ring Activity, Spencer Hill

UNLV Theses, Dissertations, Professional Papers, and Capstones

Ubiquitylation is a cellular regulatory system found in all eukaryotic cells, which has managed to find a role in most pathways imaginable. The system works fundamentally through the ligation of a small protein known as ubiquitin onto a substrate. Depending on the context of the ubiquitin ligation, the substrate can be directed towards a number of cellular fates, the best-studied being degradation of the substrate. While originally thought of as a signal for cellular disposal units to degrade aberrant proteins, we now know that ubiquitin plays a highly nuanced role in cellular epistasis, controlling everything from the cell cycle to …

The Perplexing Paradox Of Clostridioides (Clostridium) Difficile Infection (Cdi) - Analysis Of Anti-Germinants As Part Of Cdi Prophylaxis, Christopher Yip

UNLV Theses, Dissertations, Professional Papers, and Capstones

Clostridioides (Clostridium) difficile infections (CDI) have become the leading cause of nosocomial antibiotic-associated diarrhea worldwide. Under normal circumstances, bacteria found in the gastrointestinal tract provide a barrier against C. difficile colonization. Upon antibiotic therapy, the protective barrier is lost as the microbial community becomes depleted thus providing the opportunity for C. difficile to colonize the human gut. Exposure to taurocholate, a bile acid produced within the mammalian gastrointestinal tract, causes C. difficile spores to begin their transition, a process known as germination, from metabolically dormant structures to toxin-producing cells. As germination is required for the onset of CDI, anti-germination compounds …

Mojave Desert Ecosystem Recovery: Potency Of Biotic And Abiotic Restoration Methods In Low Elevation Plant Communities, Mary Amanda Balogh

UNLV Theses, Dissertations, Professional Papers, and Capstones

The historic and current state of land in the Mojave Desert, including land managed by the National Park Service with fundamental goals of natural resource conservation and preservation, been severely degraded by a variety of anthropogenic disturbances. Due to increasingly sporadic and unpredictable precipitation patterns, land managers struggle to implement restoration projects with high success rates and are resource-limited for post-treatment monitoring. In this study, I examined success rates of biotic (outplanting, seeding) and abiotic (soil manipulation, vertical mulch) restoration treatments on various disturbance types in the creosote-bursage (Larrea tridentata-Ambrosia dumosa), blackbrush (Coleogyne ramosissima), and Joshua tree woodland (Yucca brevifolia) …

‘Am I Turning Into A Man?’ Experiences Of Pakistani Women With Pcos, Rida E Zehra Zaidi

MSJ Capstone Projects

According to the National Institutes of Health, 20 – 25% of all regularly ovulating women have PCOS. This disorder has a range of visible symptoms including excessive weight gain, hirsutism, acne, and hair loss among others. These symptoms make it difficult for women with the syndrome to fit the femininity ideals of the society, as it demands female bodies to be slim, smart, hair less, and to have porcelain skin and regular menstrual cycles. Women with PCOS and other health problems in Pakistan spend all their lives fighting unnecessary battles. This struggle has severe impacts on their physical and mental …

Early Child Development Amid The Pandemic, Zain Saeed Siddiqui

MSJ Capstone Projects

I would like to bring to notice the importance of early child development because the early years are crucial for the development especially the skills that are going to help children succeed in life. Basically, I would like to focus on the natural development of the human being from birth to maturity, enabling children to become the transforming elements of society, leading to a harmonious and peaceful world.

Emotional well-being and social competence provide a strong foundation for emerging cognitive abilities, and together they are the bricks and mortar that comprise the foundation of human development.

Generally, development happens in …

Dynamics And Control In Spiking Neural Networks, Fuqiang Huang

McKelvey School of Engineering Theses & Dissertations

In the brain, neurons (brain cells) produce electrical impulses, or spikes, that are thought to be the substrate of information processing and computation. Through enigmatic processes, these spikes are ultimately decoded into perceptions and actions. The nature of this encoding and decoding is one of the most pervasive questions in theoretical neuroscience. In other words, what are the specific functions enacted by neural circuits, through their biophysics and dynamics? This thesis examines the dynamics of neural networks from the perspective of control theory and engineering. The pivotal concept is that of the normative synthesis of neural circuits, wherein neural dynamics …

Wheelchair Propulsion For Everyday Manual Wheelchair Users: Repetition Training And Machine Learning-Based Monitoring, Pin-Wei Chen

Arts & Sciences Electronic Theses and Dissertations

Upper limb pain and injuries are prevalent among manual wheelchair users and can restrict their participation and daily activities. Due to the high repetition and force in wheelchair propulsion, chronic wheelchair propulsion has been linked to the risk of upper limb pain and injury. Prevention of upper limb pain and injury is a high priority in wheelchair-related research. Decades of research in wheelchair propulsion biomechanics have led to clinical practice guidelines (CPG). Unfortunately, a decade after the publication of the CPG, CPG-recommended propulsion is still uncommon. Hence, for the first aim, a randomized controlled trial pilot study with two groups …

Generation And Utilization Of Diverse Memory B Cells After Flavivirus Challenges, Rachel Wong

Arts & Sciences Electronic Theses and Dissertations

Over the course of an effective immune response to an infection, two distinct B cell populations are generated to provide protection against reinfection, long-lived plasma cells (LLPCs) and memory B cells (MBCs). LLPCs and MBCs originate from germinal center (GC) B cells that have undergone B cell receptor (BCR) affinity maturation through iterative rounds of somatic hypermutation, proliferation, and selection. Thus, LLPCs and MBCs can bind to their antigen with higher affinity than their naïve B cell precursors. LLPCs constitutively secrete antibodies and can provide sterilizing immunity that pre-exists subsequent infections. MBCs, on the other hand, are quiescent and provide …

A Noncanonical Function Of The Telomerase Rna Component In Human Embryonic Stem Cells, Kirsten Ann Brenner

Arts & Sciences Electronic Theses and Dissertations

Telomeres are stretches of TTAGGG nucleotide repeats located at the ends of linear chromosomes that shorten with progressive cell division and prevent genomic instability at the cost of limiting a cell’s capacity to proliferate. This limitation can be overcome by telomerase, a ribonucleoprotein complex that elongates telomeres via reverse-transcription of the template telomerase RNA component (TERC). Recent studies have reported potential functions of TERC outside of its role in telomere maintenance. These noncanonical functions of TERC are however poorly defined, and the molecular mechanisms and biological relevance behind such functions remain elusive. Here, we generated conditional TERC knock-out human embryonic …