Life Sciences Commons^™

Development And Application Of Mass Spectrometry-Based Protein Footprinting In Structural Proteomics, Ming Cheng

Arts & Sciences Electronic Theses and Dissertations

Integral mass spectrometry (MS) has emerged as an important tool for protein structural characterization. It readouts are a broad range of structural information, including stoichiometry, interactions, conformations and conformation change, and dynamics. Protein footprinting is a pivotal component in the intergral MS toolkit.My dissertation centers around the development and application of protein footprinting to characterize protein structure. It is divided into seven chapters.Chapter 1 serves as the introduction for integral mass spectrometry in structural proteomic.In Chapter 2, we extended the fast-photochemical oxidation of proteins (FPOP) platform by adding the trifluoromethyl radical (•CF3) as a new reagent. We discovered that •CF3 …

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages And Type 2 Immunity, Nicholas N. Jarjour

Arts & Sciences Electronic Theses and Dissertations

Transcriptional control of gene expression is essential for life, tailoring protein production to development and environment to maintain organismal homeostasis. A limited set of proteins termed transcription factors are critical to this process. As our understanding of these central regulators has improved, new aspects of cell and organismal biology have been revealed. Herein, we demonstrate the importance of the transcription factor Bhlhe40 to tissue-resident macrophages, T helper type 2 cells, and type 2 immune responses, revealing novel transcriptional control of macrophages and unexpected cytokine regulation of helminth infection. We find that Bhlhe40 is cell-intrinsically required for normal proliferation of large …

Elucidating Enhancer Function In Epidermal Development And Filaggrin Loss-Of-Function Variants In African American Atopic Dermatitis, Mary Elizabeth Mathyer

Arts & Sciences Electronic Theses and Dissertations

The epidermis is the outermost tissue of the skin and provides the body’s first line of defense against external assaults. The epidermis is primarily composed of keratinocytes that terminally differentiate and rise apically toward the surface to form the semipermeable barrier of the skin. A hallmark of keratinocyte terminal differentiation is the expression of genes from the Epidermal Differentiation Complex (EDC) locus. Many of the EDC protein products contribute to the structural integrity of the skin barrier, evidenced by several gene knockouts such as loricrin, and even genetic variation within gene coding sequences, that modulate the integrity of the skin …

Genomic Contributors To Individual Differences In Reward-Related Neural Activity, Lindsay Jane Michalski

Arts & Sciences Electronic Theses and Dissertations

Aberrant reward-related behavior, including impulsive and risk-taking behaviors, is a common feature of externalizing psychopathology (e.g., attention deficit hyperactivity disorder, antisocial personality disorder, and substance-use disorders). Through imaging studies, these behaviors have been linked to dysregulated reactivity within a diffuse reward-related corticostriatal neural network, including the striatum, frontal regions (namely orbital, ventromedial, and dorsolateral cortices), the insula, and the hippocampus. Because variability in risk-taking behavior and related psychopathology is moderately-to-largely heritable (i.e., with estimates ranging from 40 – 80%), a genetically-informed approach is well-positioned to provide valuable insight into the etiology of reward-related neural and behavioral phenotypes that characterize externalizing …

Physiologic And Pathologic Profiling Of Clonal Variations, Wing Hing Wong

Arts & Sciences Electronic Theses and Dissertations

This thesis sought to provide a better understanding of clonality in various malignant and non-malignant settings using a variety of genomic analytical tools. Clonality is pre-defined as the presence of a mixed population of cells in which each sub-population has distinct somatic mutation profile. It is a common feature in cancers where subpopulations of cells arise as a result of independent, yet continual acquisition of somatic mutations. The clonal architecture of cancers can be used as a diagnostic and prognostic biomarker as well as to monitor disease progression or resolution. Besides cancer, clonal variability and expansion is also implicated in …

Rhodococcus Opacus Pd630 Genetic Tool Development To Enable The Conversion Of Biomass, Drew Michael Delorenzo

McKelvey School of Engineering Theses & Dissertations

The discovery of fossil fuels facilitated a new era in human history and allowed many firsts, such as the mass production of goods, the ability to travel and communicate long distances, the formation of population dense cities, and unprecedented improvements in quality of life. Alternative sources of energy and chemicals are needed, however, as hydrocarbon reserves continue to deplete and the effects of burning fossils on the planet become better understood. Lignocellulosic biomass is the most abundant raw material in the world and a viable alternative to petroleum-derived products. The pre-treatment of lignocellulose (e.g., thermocatalytic depolymerization, enzymatic hydrolysis, pyrolysis, etc.) …

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 …

A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang

McKelvey School of Engineering Theses & Dissertations

Twenty million Americans suffer from peripheral nerve injury (PNI) caused by trauma and medical disorders, with approximately $150 billion spent in annual health-care dollars in the United States. Even with proper surgical reconstruction, less than 50% of the patients achieve satisfactory functional recovery. The gold standard surgical repair for long gaps (>3cm) is the autologous nerve graft, despite its disadvantages such as donor site morbidity, risk of infection, and increased cost. Alternative methods, such as acellular nerve grafts (ANA), are ineffective for large lesion gaps because of the lack of cells and regeneration factors. Recent efforts have been focused …

Structural And Tissue-Level Adaptations Of Lumbar Intervertebral Discs In Humans With Inducible Low Back Pain Symptoms, Christian Isaiah Weber

McKelvey School of Engineering Theses & Dissertations

Low back pain (LBP) is a devastating musculoskeletal ailment that impacts majority of the global population. Up to 95% of cases are considered nonspecific where the origin is unclear. Although there is a diagnosis with these cases, there lacks specificity that would help individuals with treatment and pain management. Imaging techniques such as magnetic resonance imaging (MRI) are primarily utilized in the diagnosis of LBP as it illuminates internal structures of the spine. One important structure clearly identified with MRI is the intervertebral disc (IVD) that is susceptible to injury and disease. Further, diagnostic imaging is performed lying down where …

Landscape Scale: Inter- And Intraspecific Variation In Plant Interactions Along A Stress Gradient In The Sheep Range Of Nevada, Jordan Dowell

UNLV Theses, Dissertations, Professional Papers, and Capstones

Impending threats to shrubland ecosystems, posed by climate change, necessitate niche modeling efforts to project vegetation range shifts. However, efforts often remain unguided by individual-scale interspecific plant interactions. The stress gradient hypothesis posits that facilitation should increase in areas of high abiotic stress, only if the individuals are able to ameliorate the surrounding area via functional traits. The Sheep Range of Nevada was used to assess the role of functional traits as predictors of plant association. Larrea tridentata, Coleogyne ramosissima, and Artemisia nova were selected as shrubs with variable life history strategies and ranges in order to identify general patterns …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

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 …

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 …

Transcriptional Regulation Of Adipose Tissue Development By Pexrap And Med19, John Dean

Arts & Sciences Electronic Theses and Dissertations

Targeting adipose tissue function to decrease adiposity and improve insulin sensitivity could treat obesity and diabetes. How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat (BAT and WAT), as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis.Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its …

An Evolving Epigenome That Determines Tissue And Cell Specificity, Renee Louise Sears

Arts & Sciences Electronic Theses and Dissertations

Understanding the mechanisms driving phenotypic variation is a major goal of biology that unifies classical genetics with the emerging fields of genomics and epigenomics. Human and mouse share over 90% of genes and global tissue-specific patterns of expression are maintained between the species. Thus, it is hypothesized that gene expression is influenced through distinctive regulation among species in order to account for the unmistakable phenotypic divergence. DNA methylation, histone modifications, open chromatin patterns, transcription factor binding, and other epigenetic factors are all associated with shaping, maintaining, and repressing regulatory regions which in turn coordinate gene expression. It is vital to …

Discovering Motor Phenotypes In Autism Spectrum Disorder: A Cross-Syndrome Approach, Daniel Edwin Lidstone

UNLV Theses, Dissertations, Professional Papers, and Capstones

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a behavioral phenotype characterized by persistent deficits in social communication and social interaction accompanied by restricted, repetitive patterns of behaviors, interests, or activities. Currently in the US, approximately 2.5% of children have a diagnosis of ASD. The etiology of ASD is complex, however the disorder does have a strong genetic basis. Specific genetic mutations can lead to neuroanatomical and neurophysiological changes during development resulting in a behavioral phenotype that falls along the ASD spectrum and may result in a diagnosis of ASD. The severity of ASD-specific behaviors falls on a continuum …

The Effect Of Pleistocene Glacial - Interglacial Cycles On Patterns Of Genetic Diversity And Differentiation Of Populations Of Leptodactylus Albilabris (White-Lipped Frog) In The Puerto Rican Bank, Andre Nguyen

UNLV Theses, Dissertations, Professional Papers, and Capstones

The historical distributional shifts of various species have been attributed to the glacial-interglacial cycles of the Pleistocene Epoch (2.6 mya – 10,000 ya). Sea level changes caused by Pleistocene glacial-interglacial cycles impacted the total area of landmasses, particularly in island systems. Cooler, glacial periods increased emergent (subaerial) island area via lower sea levels. Adjacent islands may have become connected through emergent land bridges, resulting in a larger subaerial landmass. Warmer interglacial periods led to higher sea levels, which in turn reduced island area, and in some cases, submerged land bridges, fragmenting larger islands into separate, smaller units. The Puerto Rican …

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) …

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 …

Long-Term Study Of Prescribed Fire Effects On Stand Dynamics And Oak Regeneration Potentials In Degraded Upland Oak-Hickory Stands In Northwestern Arkansas, Mason C. Danheim, Kathryn R. Kidd Dr, Hal O. Liechty Dr, Brian P. Oswald Dr

Electronic Theses and Dissertations

Upland oak-hickory forests in the Ozark Mountains of northwestern Arkansas and south central Missouri were impacted by oak decline during the early 2000s. This decline event was caused by predisposing (e.g., mature, dense stand conditions), inciting (i.e., drought), and contributing (e.g., red oak borer, E. rufulus H., outbreak) factors. Immediately following onset of the decline, substantial crown dieback and tree mortality, particularly for two red oak species (northern red oak, Quercus rubra Michx. and black oak, Q. velutina Lam.), were observed. In addition, densities of advanced oak regeneration were inadequate at this time, resulting in poor regeneration potentials for …

Feeding The Future Meat Doesn’T Come Cheap, Lukas C. Southard

Capstones

Cultured – or as it is referred to by companies innovating the technology clean – meat is expected to be the next innovation to change the way the world gets its animal protein. Meat from animal cells grown in a lab seems like science fiction but it is around the corner from hitting your supermarket shelves. The technology has been developed but how these companies intend on scaling up their production to meet retail demands remains a mystery. So far companies have relied on seed and early stage investment from venture capital companies and private sources to fund research. Predictions …

Pre-Juvenile Naked Goby (Gobiosoma Bosc) Age And Growth, Annamaria Deitz, Juliana Harding

Honors Theses

Due to the abundance of larval naked gobies, Gobiosoma bosc, within the estuarine ichthyoplankton, it is important to understand their age and growth. Naked gobies are a largely distributed, both geographically and within an estuary, small, benthic fish species. There are 3 pairs of otoliths, calcium carbonate structures within the ear canal, that detect vibrations and record the age of the fish, both daily and annually. Using laboratory-reared gobies of a known age (Tremont et al. 2015), daily signatures on the sagittal otoliths were first validated to be daily, then a growth curve for the wild caught larvae was …

What If The Key To Climate Change Is Hiding Under The Sea?, Shira Feder

Capstones

“We know more about outer space than we do the ocean,” says Vicki Ferrini, a research scientist at Columbia University with over 20 ocean expeditions under her belt. And as the woman leading Seabed 2030, the charge to map the world’s oceans—which are 85% unexplored—she knows how vital this is to combat climate change and exactly how she’s going to do it. Read it here: https://medium.com/@shira.feder/what-if-the-key-to-climate-change-is-hiding-under-the-sea-4503565c33a2

Maternal Immunity: Preimplantation Preparation And Spatial Distribution Of Ccl19, Ashleigh Elbert

Electronic Theses & Dissertations

Maternal Immunity: Preimplantation preparation and the role of CCL19

An Abstract of the thesis by

Ashleigh R. Elbert

The maternal uterus in mammals undergoes extensive remodeling in preparation for implantation of the semi-allogenic embryo. Activation of the T cell homing receptor, CCR7, regulates multiple aspects of adaptive immunity. Genetic deletion of CCR7 reduces T regulatory (T Reg) cell migration into mouse uteri and decreases embryo implantation. CCL19 and CCL21 are the sole ligands for CCR7. It is hypothesized that CCL19 expression could attract T reg cells into the pre-implantation uterus and provide local immune suppression prior to implantation. Sprague Dawley …

Investigating The Relationship Between Hormone Receptors Dax-1 And Estrogen Receptor Within Prostate Cancer Cell Lines, Meghana G. Vijayraghavan

Master's Theses

Prostate cancer (PCa) is estimated to be the second leading cause of cancer-related deaths among men in the United States in 2019. While most prostate tumors rely on androgens for growth signaling, there are subsets of tumors that become androgen-resistant, therefore resisting conventional androgen-depravation therapy. Consequently, research has focused on targeting different hormone receptors for novel therapeutics. One such receptor is Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX-1). DAX-1 is known to interact with other hormone receptors, such as androgen receptor (AR) and estrogen receptors (ERs) to suppress the proliferative effects …

California Stream Condition Index (Csci) Score Analysis Of Streams Sampled From 1998 To 2017 In The San Francisco Bay Region, Jenna Rais

Master's Projects and Capstones

Human impacts to California’s streams have altered the state’s riparian and hydrological landscape. This is a critical issue with regard to natural resources, including ecosystem services such as water availability and water quality. Regulations have a limited amount of impact on the improvement of this landscape and can also become complicated by politics. Scientific advances have developed ways to quantify and describe the quality of streams, this includes the development of the California Stream Condition Index (CSCI) which is based on benthic macroinvertebrate (BMI) population numbers and functions. This index allows scientists to not only score the quality of a …

Vaxinsight: An Artificial Intelligence System To Access Large-Scale Public Perceptions Of Vaccination From Social Media, Jingcheng Du

Dissertations & Theses (Open Access)

Vaccination is considered one of the greatest public health achievements of the 20th century. A high vaccination rate is required to reduce the prevalence and incidence of vaccine-preventable diseases. However, in the last two decades, there has been a significant and increasing number of people who refuse or delay getting vaccinated and who prohibit their children from receiving vaccinations. Importantly, under-vaccination is associated with infectious disease outbreaks. A good understanding of public perceptions regarding vaccinations is important if we are to develop effective vaccination promotion strategies. Traditional methods of research, such as surveys, suffer limitations that impede our understanding of …

Quantification Of Neuronal Specific Responses To Depletion Of The Nascent Polypeptide-Associated Complex In Caenorhabditis Elegans, Harrison Hall

Senior Honors Projects, 2010-2019

Cells experiencing misfolded protein stress can become debilitated and die, consistent with this stress being linked to numerous diseases. When misfolded proteins accumulate in the endoplasmic reticulum (ER), the unfolded protein response (UPR) initiates mechanisms that resolve this stress or trigger apoptosis, dependent on the severity and/or duration of the stress. The nascent polypeptide-associated complex (NAC) is a heterodimeric chaperone that mediates proper protein folding and localization during translation; depletion of the NAC promotes misfolded protein stress in the ER, resulting in the initiation of the UPR in affected cells. The relationship between the NAC and the UPR is not …

Best Management Practices For The Conservation Of Western Pond Turtle Populations In California, Cristina Yarnal

Master's Projects and Capstones

This project provides insight into western pond turtle (Actinemys marmorata) population health at sites in three states on the western part of the United States. Washington, Oregon and California have identified the western pond turtle as endangered, a critical and a species of special concern in that respective order. Washington has implemented a recovery plan for western pond turtles and Oregon has established best management practices for the conservation of native turtles. California has yet to establish any guidelines for the conservation of western pond turtles. This species is endemic to the western United States and has been …