Life Sciences Commons^™

From Bugs To Drugs: Bacterial 3-Iaa Enhances Efficacy Of Chemotherapy In Pancreatic Cancer, Y David Seo, Jennifer A Wargo

Faculty, Staff and Student Publications

Tintelnot et al. identified enrichment of indole-3-acetic acid (3-IAA), a tryptophan metabolite produced by gut microbiota, as a predictor of chemotherapy response in pancreatic adenocarcinoma. Recapitulated in mouse models, 3-IAA represents a novel potential therapeutic approach for chemotherapy sensitization.

Comprehensive Investigation Of The Role Of Cd38 In Ovarian Nad+ Metabolism And Reproductive Aging, Lauren Haky

Natural Sciences and Mathematics | Biological Sciences Master's Theses

Nicotinamide adenine dinucleotide (NAD+) is a cofactor and coenzyme found in all living cells and is crucial for energy metabolism and tissue homeostasis. It is well documented that several tissues exhibit an age-related NAD+ decline which is strongly associated with aging and age-associated diseases. While the underlying cause of NAD+ decline is unknown, one possibility is that the major NAD+ consuming enzyme, CD38, may drive tissue NAD+ decline during aging. Several studies have previously reported that NAD+ precursor supplementation or CD38 inhibition increased tissue NAD+ levels, overall health, and lifespan in mice.

Women experience an irreversible decline in reproductive health …

Effects Of Membrane Components On The Oligomerization Of Amyloid-Β (Aβ) In Alzheimer Disease, Jhinuk Saha

Dissertations

Deposition of extracellular proteinaceous plaques of amyloid-β (Aβ) is one of the major hallmarks of Alzheimer disease (AD). Although, insoluble high molecular fibrils of Aβ are the main constituents of the senile plaques in AD, low molecular weight soluble Aβ oligomers have emerged as the key toxic species involved in memory impairment and neuronal cell death in AD. The process for generation of oligomers can be highly diverse and can involve homotypic interactions of Aβ as well as heterotypic interaction of Aβ with other macromolecules. Previously, the generation of Aβ oligomers with distinct biochemical and biophysical characteristics catalyzed non-esterified fatty …

Improved Synthesis And Anticancer Activity Of A Potent Neuronal Nitric Oxide Synthase Inhibitor, Dhananjayan Vasu, Cory T. Reidl, Eric Wang, Sun Yang, Richard B. Silverman

Pharmacy Faculty Articles and Research

An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Prostaglandin F2Α Regulates Mitochondrial Dynamics And Mitophagy In The Bovine Corpus Luteum, Michele R. Plewes, Emilia Przygrodzka, Corrine F. Monaco, Alexandria P. Snider, Jessica Jessica Keane, Patrick D. Burns, Jennifer R. Wood, Andrea S. Cupp, John S. Davis

Department of Animal Science: Faculty Publications

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, …

The Effects Of Aluminum Ion Exposure On Planarian Photophobic Response To Different Wavelengths Of Light, Anden J. Velez

Graduate Student Dissertations, Theses, Capstones, and Portfolios

Aluminum exposure has been linked to the development of neurological diseases (Kim et al., 2021). It has increased in quantity in the environment due to industrial activity in producing personal care products and fast food (Tietz et al., 2019). The freshwater invertebrate planarian flatworm Giardia dorotocephala (G. dorotocephala) serves as a model organism. Humans and planarians both express the ion channel transient receptor potential ankyrin 1 (TRPA1), which is responsible for thermotaxis, locomotive response to heat, and pain reception (Arenas et al., 2017). Aluminum exposure can exert ion channel-related toxicity via the TRPA1 protein. It has been found …

Investigating The Role Of Tgf-Beta Signaling In Acoel Regeneration & Fission, Franchesca A. Aziz

Undergraduate Honors Theses

Whole-body regeneration and asexual reproduction are widespread in the Metazoa, yet little is known about the genetic systems that drive the regeneration process outside of a few model organisms. While many animals utilize fission followed by regeneration to accomplish asexual reproduction, Convolutriloba longifissura is unusual in performing a double fission, requiring significant anterior-posterior and medial-lateral regeneration that alters the orthogonal body axes in adult tissues. To better understand the process of axial re-specification during postembryonic development, we studied the genetic mechanisms used by C. longifissura to modify and respecify axial polarity during asexual reproduction and subsequent regeneration. Because conserved signaling …

Secondary Channel Backwaters May Be Superior Nurseries For Native Fishes In The San Juan River Of The American Southwest, But Monsoon-Driven Deteriorations May Lessen Their Quality, Blake Hansen

Electronic Theses & Dissertations

The Razorback Sucker (Xyrauchen texanus) and Colorado Pikeminnow (Ptychocheilus lucius) are federally-endangered species occurring in the San Juan River of NM, CO, and UT, USA. These species have shown little natural recruitment in this system, with a lack of high-quality nursery habitats being one potential explanation for this phenomenon. The young-of-year of both species prefer backwaters, including those that form in secondary channels or in association with islands. However, it is unknown how factors that could limit imperiled fish recruitment, such as hydrologic stability, physicochemical features, resource availability, and nonnative fish densities, differ between secondary channel …

Assessing Paleoenvironmental Change Of A Boca Raton Inlet Through Midden Shell Artifact Analysis, Maria Gabriella Almeida

Graduate Student Dissertations, Theses, Capstones, and Portfolios

In this archeological study of a barrier island shell midden in Boca Raton, FL, we evaluate possible environmental and cultural changes that occurred through time by performing a quantitative analysis of shell artifacts of Giant False Donax (Iphigenia brasiliana) and Common Atlantic Oyster (Crassostrea virginica) collected from the shell midden. Middens are archeological trash sites used by researchers to identify artifacts used by past populations to understand their behaviors. The artifacts collected in shallow portion of the midden are younger (therein representing more recent time periods) and the artifacts collected at the deeper portion are older …

Evaluating Abiotic And Biotic Factors Affecting Plant Succession Processes At Malheur Lake, Beth Boos, Sammy L. King

LSU Master's Theses

Arid wetlands are diverse systems that provide habitat for a variety of flora and fauna, including stopover and breeding habitat for migratory birds. In the western United States, these wetlands support a network of stopover sites on the Pacific Flyway, and due primarily to wetland loss and alterations, these areas are becoming more isolated. Malheur Lake is a shallow endorheic lake in eastern Oregon that supported a robust emergent marsh throughout most of the 20^th century. However, following large scale flooding in the 1980s, emergent vegetation was extirpated and has only reestablished in small patches. Our objective was to …

Development And Validation Of An Ultrahigh-Performance Liquid Chromatography–Tandem Mass Spectrometry Method To Investigate The Plasma Pharmacokinetics Of A KCa2.2/KCa2.3 Positive Allosteric Modulator In Mice, Mohammad Asikur Rahman, Devaraj Venkatapura Chandrashekar, Young-Woo Nam, Basir Syed, David Salehi, Hamidreza Montazeri Aliabadi, Miao Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Rationale

There is currently no treatment for spinocerebellar ataxias (SCAs), which are a group of genetic disorders that often cause a lack of coordination, difficulty walking, slurred speech, tremors, and eventually death. Activation of K_Ca2.2/K_Ca2.3 channels reportedly exerts beneficial effects in SCAs. Here, we report the development and validation of an analytical method for quantitating a recently developed positive allosteric modulator of K_Ca2.2/K_Ca2.3 channels (compound 2q) in mouse plasma.

Methods

Mouse plasma samples (10 μL) containing various concentrations of 2q were subjected to protein precipitation in the presence of a structurally similar …

Spike-Timing-Dependent Plasticity Alters Sensory Network Connectivity, Adalee Lube

Arts & Sciences Graduate Student Theses and Dissertations

A fundamental question in neuroscience is: how does a sensory system optimize detection of behaviorally relevant stimuli, when those stimuli and the sensory environment are constantly changing? Spike-timing-dependent plasticity (STDP), in which synapse strength changes based on the relative timing of pre- and post-synaptic spiking, has been implicated in changes in neuronal connectivity thought to underlie learning and memory. Synaptic strength changes caused by STDP have been shown in optic tectum, visual cortex, hippocampus, and other brain regions in vitro across many organisms like fish, frogs, and mice. Although it is possible that STDP mechanisms underlie changes in sensory neuron …

An Evolving View Of Host-Microbiome Co-Development In Healthy And Undernourished Children, Robert Yuzen Chen

Arts & Sciences Graduate Student Theses and Dissertations

Affecting more than 795 million children under the age of 5, childhood undernutrition is one of the greatest impediments to the flourishing of humankind. Current dietary interventions fail to ameliorate many of the long-term sequelae of undernutrition, including immune system dysfunction, impaired vaccine responses, persistent central nervous system (CNS) dysfunction, and early mortality. These shortcomings suggest that our understanding of the biological state of undernutrition is incomplete, and that traditional food therapies fail to target key drivers of undernutrition-dependent pathologies. Recently, work from our lab has provided preclinical evidence demonstrating that impaired development of the distal gut microbiota plays a …

A Mechanistic Study Of Err Α/Γ Agonists For Treatment Of Metabolic Dysfunction In Heart Failure, Mckenna Lael Losby

Arts & Sciences Graduate Student Theses and Dissertations

Heart failure is the leading cause of death in the United States and current therapeutic interventions fail to reverse the disease progression. In the failing heart, pathological cardiac remodeling leads to disease progression: a process characterized by hypertrophy, inflammation, fibrosis, and metabolic remodeling. By pharmacologically targeting the nuclear hormone receptors estrogen receptor-related receptor α and γ (ERRα and γ), it may be possible to reverse the array of metabolic pathways that are pathologically inhibited in the failing heart. Fatty acids are the primary fuel source of the adult heart that generate the ATP required for each contraction; however, in heart …

Histamine Production By Airway Resident Haemophilus Species Induces Rhinitis, Michael Lint

Arts & Sciences Graduate Student Theses and Dissertations

Allergic rhinitis is one of the most common chronic illnesses in America, affecting more than 60 million people each year. Allergies develop when sensitization to an environmental allergen result in the production of antigen-specific IgE. Subsequent exposure to the allergen, detected by IgE, then binds to the surface of mast cells triggering the release of inflammatory mediators particularly histamine, which contribute to characteristic allergic symptoms of nasal itching, sneezing, and wheezing. Although fundamental mechanisms underlying allergy development have been previously characterized, recent research has implicated commensal bacteria residing in the respiratory tract in contributing to the development of allergic inflammation, …

Mechanisms And Consequences Of Microtubule-Based Symmetry Breaking In Plant Roots, Natasha Anriel Bilkey

Arts & Sciences Graduate Student Theses and Dissertations

Directional growth in plants is primarily determined by the axis of cell expansion, which is specified by the net orientation of cortical microtubules. Microtubules guide the deposition of cellulose and other cell wall materials. In rapidly elongating cells, transversely oriented microtubules create material anisotropy in the cell wall that prevents radial cell expansion, channeling cell expansion in the longitudinal direction. Mutations perturbing microtubule organization frequently lead to aberrant cell growth in land plants, with some mutations leading to helical growth patterns (called ‘twisted mutants’), often in roots. This phenotype manifests as right-handed or left-handed twisting of cell files along the …

Understanding The Spectrum Of Dnmt3a Mutations In Neurodevelopmental Disease, Diana Christian Beard

Arts & Sciences Graduate Student Theses and Dissertations

Epigenetic mechanisms are critical for precisely controlling gene expression programs to allow for the development and function of the brain, and disruptions of these processes are highly associated with neurodevelopmental disease. DNA methylation is one mechanism used to regulate gene expression, and neurons employ a unique form of DNA methylation particularly at CA dinucleotides (mCA), that is not widely observed in other somatic cell types. The DNA methyltransferase DNMT3A is required to establish mCA, and mutations in DNMT3A are associated with autism spectrum disorder (ASD) and an overgrowth and intellectual disability disorder called Tatton-Brown Rahman Syndrome (TBRS). However, it remains …

Investigating Disease Progression And Therapeutic Targets In Multiple Myeloma Using Single-Cell Technologies, Lijun Yao

Arts & Sciences Graduate Student Theses and Dissertations

Multiple Myeloma (MM) is a highly heterogeneous disease characterized by uncontrolled clonal expansion of plasma cells. Single-cell techniques are advantageous in providing a more granular understanding of inter- and intratumoral genomics and surrounding microenvironments. The high relapse rate and intrinsic complexity of MM make the application of single-cell technologies particularly beneficial. Understanding the concordance of the measurements across single cell techniques in MM is of great interest. In this dissertation, we first integrated three single-cell technologies, namely scRNA-seq, CyTOF, and CITE-seq, to characterize MM immune microenvironment and assess their concordances of measurement. Overall, cell type abundances were relatively consistent, while …

Single-Molecule Spectroscopy Of The Sars-Cov-2 Nucleocapsid Protein, Jasmine Cubuk

Arts & Sciences Graduate Student Theses and Dissertations

The COVID pandemic has affected over 760,000,000 individuals worldwide since late 2019. Understanding how SARS-CoV-2, the virus responsible for the disease, functions at a mechanistic level is essential to develop therapeutics and vaccines. SARS-CoV-2 utilizes four structural proteins that work together during the viral life cycle to ensure the spread of infections: spike (S), envelope (E), membrane (M) and nucleocapsid (N). Though much work has focused on the S protein for the purpose of vaccines, the N protein plays a key function in the viral life cycle as well. Nucleocapsid is responsible for packaging the viral genome and incorporating the …

Bioinformatic Tools To Alleviate The Annotation Bottleneck Within Precision Oncology, Erica Kay Barnell

Arts & Sciences Graduate Student Theses and Dissertations

In the era of advanced ability to perform complex genomic sequencing, precision oncology has been adopted as the ideal paradigm for optimization of outcomes for patients with cancer. However, despite technological advances in all aspects of the massively parallel sequencing pipeline, the application of precision oncology to every clinical workflow has been unattainable. Suboptimal adoption of custom medicine within oncology is attributable to the annotation bottleneck, which currently demands inordinate manual and computational requirements for completion. Alleviation of the annotation bottleneck requires co-development of bioinformatic strategies and analysis knowledgebanks to automate variant identification and variant annotation for clinical utility. The …

The Influence Of The Gut Microbiota On Asthma In School-Aged Children And Adults, Naomi Grace Wilson

Arts & Sciences Graduate Student Theses and Dissertations

Asthma is a common respiratory disease with a highly heterogeneous pathophysiology. The human gut microbiota, comprising of all the microorganisms that inhabit the gastrointestinal tract, is linked to the development of asthma and can alter airway inflammation in animal models. The idea that the gut microbiota can have bidirectional cross-talk with the lung, such as gut dysbiosis affecting lung disease, is termed the gut-lung axis. While the gut microbiota of early life has been an area of particular interest for asthma pathogenesis research, the effect of its taxonomic and functional composition after asthma diagnosis is less clear. This dissertation employs …

Mechanisms Of Transcription Regulation By Card In Mycobacterium, Dennis Xiaoqian Zhu

Arts & Sciences Graduate Student Theses and Dissertations

Mycobacterium tuberculosis (Mtb) is an important human pathogen that is responsible for over 1 million deaths each year. As a bacterial pathogen, Mtb is highly adapted to survival within the host environment, which imposes numerous environmental stresses on the bacteria. To survive these challenges, Mtb utilizes a network of transcription factors to adapt its gene expression and physiology. CarD is an essential transcription factor in mycobacteria that binds directly to RNA polymerase (RNAP) rather than DNA sequence motifs on the chromosome. Prior mechanistic studies of CarD’s function in mycobacteria have been limited to studies of CarD’s effects on individual kinetic …

An Exploratory Study On Strategies Adopted By Parents Who Use E-Cigarettes To Negotiate Risk Perceptions Of Their Children's Secondhand Exposure And Parental Role Modeling, Joon Kyung Nam, Jesse P Zatloff, Su-Wei Wong, Hsien-Chang Lin, Wei-Chung Su, Anne Buu

Faculty, Staff and Student Publications

Existing health messages mainly targeted youth susceptible to vaping or parents who do not have much knowledge about e-cigarettes. This study makes a unique contribution by conducting the first in-depth investigation of e-cigarette-using parents' risk perceptions and parental role modeling and how these two factors affect their vaping behaviors at home or implementation of any strategies to reduce their children's risk. Fifteen parents who used e-cigarettes participated in a semi-structured interview. Interview transcripts were coded and analyzed through a deductive approach of thematic analysis. This study demonstrates the need to develop and disseminate future health messages for e-cigarette-using parents who …

Evaluating The Impact Of Temperature And Artificial Light At Night On The Growth, Swimming Performance, And Corticosterone Levels Of Southern Leopard Frog (Lithobates Sphenocephalus) Tadpoles, Skylar Alexander

Honors Theses

Anthropogenic activities caused by urbanization have considerably altered our world’s ecosystems which has led to a global amphibian population decline. Encroaching and unyielding urbanization by humans has contributed to a rise in artificial light at night due to light pollution as well as increased temperature due to climate change. Both rising temperatures and artificial light at night (ALAN) have been shown to individually have negative effects on amphibian physiology such as increased stress and decreased behavior. However, due to the drastic nature of human imposition, amphibians typically encounter these anthropogenic stressors in combination. Therefore, it is important to understand how …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Graduate Student Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Agricultural Shocks On Household Stability: A Case Study Of Tanzania Maize Farmers, Zimmi Ndlovu

Master's Theses

As the global populations grow, the need for stronger agricultural resilience in areas with high food insecurity like Sub-Saharan Africa (SSA) is a must. Crop failure due to climate related events has increased substantially over the past decade, raising the risks to vulnerable groups like subsistence farmers. Understanding the effects of climate variability on farmers and their crops is a pivotal step towards increasing resilience and productivity. In this paper I approach this question using a Linear Probability Fixed-effects Model on Tanzanian Panel Survey data with monthly temperature and precipitation for years 2008 to 2013. Results suggest a negative relationship …

Anillin And Dunk: The Conserved And Non-Conserved Players Regulating Myosin Dynamics In Drosophila Cleavage, Jiayang Chen

Dartmouth College Ph.D Dissertations

Cleavage is a common process during early embryogenesis. Similar to conventional cytokinesis, Drosophila cellularization, a unique form of cleavage, requires precise regulation of non-muscle myosin II ("myosin") at cleavage furrows, where myosin forms an interconnected basal array before reorganizing into individual cytokinetic rings. However, how myosin is regulated through both conserved and cellularization-specific mechanisms during this special form of cytokinesis remains unclear.

In my first project, I investigated the molecular mechanisms by which the cellularization-specific zygotic gene dunk regulates myosin at the basal array. I identified anillin (Scraps in Drosophila), a conserved scaffolding protein in cytokinesis, as the primary …

Single-Molecule Super-Resolution Imaging Of Geobacter Sulfurreducens Under Anaerobic Conditions, Ziyi Hu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Geobacter sulfurreducens are anaerobic bacteria capable of making electrical contacts with other organisms and extracellular electron acceptors. The challenge of imaging live Geobacter bacteria is maintaining anaerobic conditions during the imaging process. In this thesis, we augment a single-molecule localization microscope (SMLM) with a home-built anaerobic imaging chamber and use constant argon bubbling to maintain oxygen-free imaging conditions. To validate the imaging protocol, we use the transient binding of Nile red to resolve the spherical morphology of lipid-coated glass spheres with nanoscale resolution. However, when imaging Geobacter, the distribution of Nile red localizations is non-uniform, both between different cells …

Manage Your Money Wisely: How Consumers And Marketers Can Effectively Communicate Money Issues, Alexander Park

Olin Business School Graduate Student Theses and Dissertations

Consumers and marketers find it challenging to communicate money matters. For example, consumers experience discomfort and uneasiness when discussing financial issues with their social relationships. Firms often receive backlash when sharing their good financial deeds (e.g., charitable efforts) with consumers. Because financial matters can be a sensitive topic, in my research, I explore the difficulties consumers and marketers experience when communicating money issues and how they can better navigate these problems.In Chapter One, I investigate a particularly uneasy interaction that consumers often face with their friends and acquaintances: the need to ask for money back. Seven fully preregistered studies (N …