Life Sciences Commons^™

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. …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

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. …

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 …

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 …

Transcription Regulation Of Human Il1b Gene In Monocytes And Lymphoid Cd4 T Cells, Sree H. Pulugulla

Electronic Theses and Dissertations

Cytokines are key regulators of the inflammatory response and play an important role in facilitating intercellular communication between various immune cell types. Interleukin‑1β (IL‑1β) is a potent pro-inflammatory cytokine that is required for robust initiation of innate immune response and subsequent development of adaptive immunity. IL-1β is first synthesized as an inactive cytoplasmic, non‑glycosylated, precursor molecule (proIL‑1β) by monocytes and macrophages in response to invading pathogenic microbes. The activation of caspase‑1 by inflammasomes cleaves proIL-1β into mature biologically active IL-1β that is released from cells via a non-classical, endoplasmic reticulum‑independent secretory pathway directly from the cytoplasm via Gasdermin D membrane …

Genetic And Biochemical Analysis Of A Conserved, Multi-Gene System Regulation Spore-Associated Proteins In Streptomyces Coelicolor, Joseph Sallmen

Electronic Theses and Dissertations

Streptomyces coelicolor is a Gram positive, filamentous soil dwelling bacterium that exhibits a complex life cycle including the transition from a vegetative mycelium to a sporulating, aerial mycelium. Early genetic studies identified two classes of genes that resulted in developmental blocks, bald and white. The bald (bld) phenotype occurs when colonies cannot produce aerial hyphae. White (whi) colonies exhibit incomplete sporulation and/or loss of production of the concurrently produced grey pigment. While some of the original mutants have been explored, the developmental functions of many of the identified genes are not well understood. Of particular interest …

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain …

A Transcriptomic Exploration Of Hawaiian Drosophilid Development And Evolution, Madeline M. Chenevert

LSU New Orleans Theses and Dissertations

One in four known species of fruit flies inhabit the Hawaiian Islands. From a small number of colonizing flies, a wide range of species evolved, some of which managed to reverse-colonize other continental environments. In order to explore the developmental pathways, which separate the Hawaiian Drosophila proper and the Scaptomyza group that contains reverse-colonized species, the transcriptomes of two better-known species in each group, Scaptomyza anomala and Drosophila grimshawi, were analyzed to find changes in gene expression between the two groups. This study describes a novel transcriptome for S. anomala studies as well as unusual changes in gene expression …

The Vezo Communities And Fisheries Of The Coral Reef Ecosystem In The Bay Of Ranobe, Madagascar, Shane Abeare

LSU New Orleans Theses and Dissertations

Madagascar, a country whose extraordinary levels of endemism and biodiversity are celebrated globally by scientists and laymen alike, yet historically has received surprisingly little research attention, is the setting of the present dissertation. Here, I contribute to the need for applied research by: 1) focusing on the most intensely fished section of the Toliara Barrier Reef, the Bay of Ranobe; 2) characterizing the marine environment, the human population, and the fisheries; and 3) collecting the longest known time-series of data on fisheries of Madagascar, thereby providing a useful baseline for future analyses. In Chapter 1, the bathymetry of the Bay …

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

LSU 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 …

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. …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

State-Dependent Mapping Of Glyr-Cholesterol Interactions By Coupling Crosslinking With Mass Spectrometry, Nicholas Ferraro

Electronic Theses and Dissertations

The glycine receptor (GlyR) belongs to a superfamily of pentameric ligand-gated ion channels (pLGICs) that mediate fast neurotransmission. GlyR typically modulates inhibitory transmission by antagonizing membrane depolarization through anion influx. Allosteric interactions between the receptor and its lipid surroundings affect receptor function, and cholesterol is essential for pLGIC activity. Human α1 GlyR was purified from baculovirus infected insect cells and reconstituted in unilamellar vesicles at cholesterol: lipid ratios below and above the cholesterol activity threshold with aliquots of azi-cholesterol. State-dependent crosslinking studies of receptors primarily in its resting (no glycine), desensitized (10mM glycine) and open (F207A/A288G, 30nM ivermectin) states were …

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

A 100-M-Scale Modeling Study Of A Gale Event On The Lee Side Of A Long Narrow Mountain, Halie Xue, Jian Li, Tingting Qian, Hongping Gu

Plants, Soils, and Climate Faculty Publications

In this study, a gale event that occurred on the lee side of a long narrow mountain was investigated, together with the associated mountain flows, using a realistic-case large-eddy simulation (LES) that is based on the Weather Research and Forecasting Model. The mountain is located on the southeastern Tibetan Plateau, where approximately 58 gales occur annually, mostly in the afternoons during the winter season. Benefitting from realistic topography and high horizontal resolution as fine as 111 m, the LES can replicate features similar to the wind fields observed during the gale period. Investigation of the early morning wind structure over …

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 …

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 …

Towards A “Rescue Ready” Mindset: Can Lifeguard Teams Learn Lessons From The Attributes Of Chronic Unease?, Billy Rj Doyle, Jonathon Webber

International Journal of Aquatic Research and Education

Highly Reliable Organisations (HROs) are safety-centric organisations that operate in complex environments alongside risky technologies and processes. There is a high risk of catastrophe and error in these settings, the consequences of which may result in loss of life, financial cost, and damage to the environment. “Chronic unease” is a concept originally adopted by Royal Dutch Shell describing a mindset that has five predictable attributes that contribute to an individual’s and organisational safety culture. The authors of this paper describe the attributes of chronic unease in the context of lifeguard operations. A case study of a dangerous and dynamic rescue …

Green Strategic Planning Approach For International Shipping Activities, Xiaofang Wu, Luoping Zhang, Huan Feng

Department of Earth and Environmental Studies Faculty Scholarship and Creative Works

Sustainability is a long-term and ultimate goal for international shipping, although it is slowly making progress. The shipping perspective that moves away from “port-to-port” operations to “door-to-door” services also requires international shipping to take a long-term and holistic view instead of fragmented efforts. How to achieve the long-term sustainability goal becomes a key issue for door-to-door international shipping. Hence, green strategic planning for door-to-door international shipping was proposed with green development that puts forward the eco-centric point of view as its basic theory for sustainability. This study used a strategic decision-making approach, a so-called multi-dimensional decision-making (MDDM), coupled with the …

Diary Of A Service Dog (Dropout), Kristen An Horton, Heidi Anne Horton Pittman

Zea E-Books Collection

My name is Granger. I am a Labrador Retriever. I want to be a service dog. It is not always easy. This is my story. (Human's note: The most important take away is that the public, children and adults, need to learn how to not interact with service dogs. As Granger says, “I’m cute. I’m working. Please ignore me.”)

Potential Distribution Of Six North American Higher-Attine Fungus-Farming Ant (Hymenoptera: Formicidae) Species, Sarah F. Senula, Joseph T. Scavetta, Joshua A. Banta, Ulrich G. Mueller, Jon N. Seal, Katrin Kellner

Biology Faculty Publications and Presentations

Ants are among the most successful insects in Earth’s evolutionary history. However, there is a lack of knowledge regarding range-limiting factors that may influence their distribution. The goal of this study was to describe the environmental factors (climate and soil types) that likely impact the ranges of five out of the eight most abundant Trachymyrmex species and the most abundant Mycetomoellerius species in the United States. Important environmental factors may allow us to better understand each species’ evolutionary history. We generated habitat suitability maps using MaxEnt for each species and identified associated most important environmental variables. We quantified niche overlap …

Divergent Phenotypic Response Of Rice Accessions To Transient Heat Stress During Early Seed Development, Puneet Paul, Balpreet K. Dhatt, Jaspreet Sandhu, Waseem Hussain, Larissa Irvin, Gota Morota, Paul E. Staswick, Harkamal Walia

Department of Agronomy and Horticulture: Faculty Publications

Increasing global surface temperatures is posing a major food security challenge. Part of the solution to address this problem is to improve crop heat resilience, especially during grain development, along with agronomic decisions such as shift in planting time and increasing crop diversification. Rice is a major food crop consumed by more than 3 billion people. For rice, thermal sensitivity of reproductive development and grain filling is well-documented, while knowledge concerning the impact of heat stress (HS) on early seed development is limited. Here, we aim to study the phenotypic variation in a set of diverse rice accessions for elucidating …

A Bifunctional Atpase Drives Tad Pilus Extension And Retraction, Courtney K. Ellison, Jingbo Kan, Jennifer L. Chlebek, Katherine R. Hummels, GaёL Panis, Patrick H. Viollier, Nicolas Biais, Ankur B. Dalia, Yves V. Brun

Publications and Research

A widespread class of prokaryotic motors powered by secretion motor adenosine triphosphatases (ATPases) drives the dynamic extension and retraction of extracellular fibers, such as type IV pili (T4P). Among these, the tight adherence (tad) pili are critical for surface sensing and biofilm formation. As for most other motors belonging to this class, how tad pili retract despite lacking a dedicated retraction motor ATPase has remained a mystery. Here, we find that a bifunctional pilus motor ATPase, CpaF, drives both activities through adenosine 5′-triphosphate (ATP) hydrolysis. We show that mutations within CpaF result in a correlated reduction in the rates of …

Representative Economic Budgets For Nebraska Cow Herds, Glennis Mcclure, Jay Parsons

Cornhusker Economics

In 2017, the University of Nebraska-Lincoln Institute of Agricultural and Natural Resources (IANR) and Nebraska Extension made a commitment to implement a multidisciplinary Beef Systems Initiative (BSI). BSI is administered by the Center for Grassland Studies and is comprised of six projects designed to develop and support implementation of beef production systems that optimize feed resource use, natural resource conservation, and producer success in Nebraska through improved management of perennial grasslands and systems of integrated crop-beef cattle production. In addition to BSI, a parallel project funded by the Foundation for Food and Agriculture Research (FFAR) is studying the best practices …

Succession Of Microbial Populations And Nitrogen-Fixation Associated With The Biodegradation Of Sediment-Oil-Agglomerates Buried In A Florida Sandy Beach, Boryoung Shin, Ioana Bociu, Max Kolton, Markus Huettel, Joel E Kostka

C-IMAGE Publications

The Deepwater Horizon (DWH) oil spill contaminated coastlines from Louisiana to Florida, burying oil up to 70 cm depth in sandy beaches, posing a potential threat to environmental and human health. The dry and nutrient-poor beach sand presents a taxing environment for microbial growth, raising the question how the biodegradation of the buried oil would proceed. Here we report the results of an in-situ experiment that (i) characterized the dominant microbial communities contained in sediment oil agglomerates (SOAs) of DWH oil buried in a North Florida sandy beach, (ii) elucidated the long-term succession of the microbial populations that developed in …

The Feasibility Of Vigorous Resistance Exercise Training In Adults With Intellectual Disabilities With Cardiovascular Disease Risk Factors, Stijn Wetering, Alyt Oppewal, Thessa I. M. Hilgenkamp

Physical Therapy Faculty Research

Background The cardiovascular disease (CVD) risk is high in adults with intellectual disabilities. This CVD risk can potentially be decreased with a resistance training (RT) programme at vigorous intensity, following previous research on successful High‐Intensity Training programmes. Our aim was to explore the feasibility of a vigorous RT‐programme for adults with intellectual disabilities with CVD risk factors. Method Twenty‐four adults with intellectual disabilities with at least one CVD risk factor participated in a 24‐week RT‐programme. The training intensity was increased from novice (50%1RM) to vigorous (75%–80%1RM). Feasibility was based on the achieved training intensity at the end of the RT‐programme. …

Management Controls The Net Greenhouse Gas Outcomes Of Growing Bioenergy Feedstocks On Marginally Productive Croplands, Virginia L. Jin, Marty Schmer, Catherine E. Stewart, Robert B. Mitchell, Candiss O. Williams, Brian J. Wienhold, Gary Varvel, Ronald F. Follett, John Kimble, Kenneth P. Vogel

United States Department of Agriculture-Agricultural Research Service / University of Nebraska-Lincoln: Faculty Publications

Bio-based energy is key to developing a globally sustainable low-carbon economy. Lignocellulosic feedstock production on marginally productive croplands is expected to provide substantial climate mitigation benefits, but long-term field research comparing greenhouse gas (GHG) outcomes during the production of annual versus perennial crop-based feedstocks is lacking. Here, we show that long-term (16 years) switchgrass (Panicum virgatum L.) systems mitigate GHG emissions during the feedstock production phase compared to GHG-neutral continuous corn (Zea mays L.) under conservation management on marginally productive cropland. Increased soil organic carbon was the major GHG sink in all feedstock systems, but net agronomic GHG outcomes …

Defects In Mating Behavior And Tail Morphology Are The Primary Cause Of Sterility In Caenorhabditis Elegans Males At High Temperature, Emily M. Nett, Nicholas B. Sepulveda, Lisa N. Petrella

Biological Sciences Faculty Research and Publications

Reproduction is a fundamental imperative of all forms of life. For all the advantages sexual reproduction confers, it has a deeply conserved flaw: it is temperature sensitive. As temperatures rise, fertility decreases. Across species, male fertility is particularly sensitive to elevated temperature. Previously, we have shown in the model nematode Caenorhabditis elegans that all males are fertile at 20°C, but almost all males have lost fertility at 27°C. Male fertility is dependent on the production of functional sperm, successful mating and transfer of sperm, and successful fertilization post-mating. To determine how male fertility is impacted by elevated temperature, we analyzed …