Animal Experimentation and Research Commons^™

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 …

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 …

Consolidated Chamber Design And Protocol For Olfactory Conditioning Assay With Drosophila Melanogaster, Sasha Bronovitskiy, Andres Castillo, Michael Yan, Fang Ju Lin

Journal of the South Carolina Academy of Science

The olfactory conditioning assay is widely used in Alzheimer’s disease research to quantify learning and memory in Drosophila melanogaster. The assay tests ability to recall an aversive conditioned stimulus of scent paired with electrical shock when presented a choice between shock-associated and unrelated scents. The T-maze, a commonly used apparatus for olfactory conditioning assays, employs an elevator mechanism to transfer live flies from the shock-delivering training chamber to the scent selection point. This elevator mechanism is known to cause fly casualty. T-mazes are not commercially available and often difficult to reproduce. Other existing variations of olfactory conditioning apparatuses use …

Comparative Analysis Of The Effects Of Actual Versus Assumed Opioid Experience On The Regulation Of Ventral Striatal Opioid Receptor Gene Expression, Indu Mithra Madhuranthakam, Martin Job

Rowan-Virtua Research Day

Rationale: We conducted experiments to assess the effect of prior opioid experience on gene expression changes. We compared the current experimenter-imposed short versus extended-access conditions of opioid self-administration and developed a new quantitative method to determine their effectiveness in identifying the role of opioid experience in regulating opioid receptor expression levels in the ventral striatum (VS) using an oxycodone self-administration/abstinence model.

Methods: In this study, male Sprague-Dawley rats (n=36) were trained for 20 days to self-administer oxycodone at 0.1 mg/kg/infusion under short access (n=15, or saline as controls n=3, for 3h/day) or extended access (n=15, or saline as controls n=3, …

Reverse Genetics: Downregulating Chk-1 And Fasn-1 In The Gonads Of C. Elegans, Sam Thompson

Undergraduate Theses

Despite its widespread use in research, the model organism C. elegans has several biological processes like gonadal development with potentially unexplored genetic regulators. Previous transcriptome analysis has identified several genes that are upregulated in a specific tissue or sex during the development of the somatic gonad in C. elegans (Kroetz et al. 2015) that have not been previously connected to this process. Of these genes, this research is concerned with chk-1 and fasn-1. Abrogating the expression of these genes in gonadal tissue during gonadogenesis could cause a change in phenotype for affected C. elegans that would aid in understanding these …

Dopamine Injections To The Midbrain Periaqueductal Gray Inhibit Vocal-Motor Production In A Teleost Fish, Alexander Allen, Elizabeth Heisler, James Matthew Kittelberger

Biology Faculty Publications

Across vertebrates, the midbrain periaqueductal gray (PAG) plays a critical role in social and vocal behavior. Dopaminergic neurotransmission also modulates these behaviors, and dopaminergic innervation of the PAG has been well documented. Nonetheless, the potential role of dopamine in shaping vocal production at the level of the PAG is not well understood. Here, we tested the hypothesis that dopamine modulates vocal production in the PAG, using a well-characterized vertebrate model system for the study of vocal communication, the plainfin midshipman fish, Porichthys notatus. We found that focal dopamine injections to the midshipman PAG rapidly and reversibly inhibited vocal production …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

An Ecological Perspective Of American Rodent-Borne Orthohantavirus Surveillance, Nathaniel Mull

Graduate Theses and Dissertations

Orthohantaviruses are a global group of viruses found primarily in rodents, though several viruses have also been found in shrews and moles. Many rodent-borne orthohantaviruses are capable of causing one of several diseases in humans, and the mortality associated with these diseases ranges from < 0.1% - 50% depending on the specific etiological virus. In North and South America, orthohantavirus research was ignited by an outbreak of severe disease in the Four Corners region of the United States in 1993. However, despite the discovery of over 20 orthohantaviruses in the Americas, our understanding of orthohantavirus ecology and virus-host dynamics in this region is still limited, and orthohantavirus surveillance is generally restricted in scope to select regions and small portions of host distributional ranges. In Chapter I, I present a literature review on the current understanding of American rodent-borne orthohantavirus ecology. This review focused on under-studied orthohantaviruses, addressing gaps in knowledge by extrapolating information from well-studied orthohantaviruses, general rodent ecology, and occassionally from Eurasian orthohantavirus-host ecology. There were several key conclusions generated from this review that warrant further research: 1) the large number of putative orthohantaviruses and gaps in orthohantavirus evolution necessitate further surveillance and characterization, 2) orthohantavirus traits differ and are more generalizable based on host taxonomy rather than geography, and 3) orthohantavirus host species are disproportionately found in grasslands and disturbed habitats. In Chapter II, I present a prioritized list of rodent species to target for orthohantavirus surveillance based on predictive modeling using machine learning. Probable orthohantavirus hosts were predicted based on traits of known orthohantavirus hosts using two different types of evidence: RT-PCR and virus isolation. Predicted host distributions were also mapped to identify geographic hotspots to spatially guide future surveillance efforts. In Chapter III, I present a framework for understanding and predicting orthohantavirus traits based on reservoir host phylogeny, as opposed to the traditional geographic dichotomy used to group orthohantaviruses. This framework establishes three distinct orthohantavirus groups: murid-borne orthohantaviruses, arvicoline-borne orthohantaviruses, and non-arvicoline cricetid-borne orthohantaviruses, which differ in several key traits, including the human disease they cause, transmission routes, and virus-host fidelity. In Chapter IV, I compare rodent communities and orthohantavirus prevalence among grassland management regimes. Sites that were periodically burned had high rodent diversity and a high proportion of grassland species. However, rodent seroprevalence for orthohantavirus was also highest in burned sites, representing a trade-off in habitat management outcomes. The high seroprevalence in burned sites is likely due to the robust populations supported by the high quality habitat resulting from prescribed burning. In Chapters V and VI, I describe Ozark virus and Sager Creek virus, two novel orthohantaviruses discovered from specimens collected during Chapter IV. Both chapters report full genome sequences of the respective viruses and compare both nucleotide and protein phylogenies with related orthohantaviruses. Additionally in Chapter VI, I support the genetic analyses with molecular and ecological characterizations, including seasonal fluctuations in host abundance, correlates of prevalence, evidence of virus shedding, and information on host cell susceptibility to Sager Creek virus.

Factors That Affect Home Range Of Timber Rattlesnakes (Crotalus Horridus) In Northwest Arkansas, Bannon Gallaher

Graduate Theses and Dissertations

Conservation of animal populations requires knowledge of their habitat and spatial needs. Quantifying spatial requirements involves the analysis of home range. We examined the effects of sex, body size (SVL), body condition (log mass/log SVL), and year on home range in Timber Rattlesnakes (Crotalus horridus) in Northwest Arkansas. Individual locality data from an ongoing, 22+ year radio-telemetry study in Madison Co., Arkansas were analyzed using both minimum convex polygon (MCP) and Kernel Density Estimates (KDE). Plots of the number of sequential observations versus home range (MCP and KDE) determined that a minimum of 25 locations per individual per active season …

Mitral Valve Imaging And Biomechanics: A Workflow Towards Computational Modeling And Validation, Sam Stephens

Graduate Theses and Dissertations

The mitral valve serves a critical role in healthy cardiac function by ensuring the unidirectional flow of oxygenated blood from the left atrium into the left ventricle. It experiences the highest pressures found within the heart and its closure is the result of a complex interaction of several different structures that, furthermore, are unique to each individual. Despite the valve’s vital role however, the specific function of these constituent structures is not fully understood. This, confounded by its asymmetric, personalized nature, make surgical interventions for the mitral valve far less effective than for its neighboring aortic valve. Efforts to overcome …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations and Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Characterizing And Evaluating Growth Performance And Poultry Production Efficiencies Using Conventional And Novel Monitoring Methods On Modern Broilers And Japanese Quail, Travis Tabler

Graduate Theses and Dissertations

The poultry industry is integral to the global agricultural system as consumption rates continue to rise worldwide. With the global population projected to reach 10 billion by 2050, there is an increasing need for efficient and sustainable animal protein sources. Feed efficiency is a significant factor in poultry production costs, as feed accounts for 50 to 70% of total production costs. Given increasing concerns surrounding feed efficiency improvements, there is a focus on the genetic improvement of broiler digestibility to improve nutrient utilization and reduce production costs. Water availability is also of critical concern for the poultry industry, as estimates …

How Much Does The Host Matter? Larval Performance Of Speyeria Butterflies On Different Hosts And Artificial Diet, Alina Nguyen, Ashlyn Chan

Pacific Undergraduate Research and Creativity Conference (PURCC)

No abstract provided.

Analysis Of Wild Rodent Gut Microbiota As A Function Of Exposure To Ticks And Tick-Borne Pathogens, Joshua Pandian

Honors Theses

Due to advances in high-throughput parallel sequencing, researchers have conducted novel studies exploring relationships between microbiome compositions and different aspects of organism health. Some of these studies have shown that the gut microbiome of rodent models has effects on organism health and behavior and that infection with pathogens and the composition of the skin microbiome are linked to changes in gut microbiome composition. While previous studies have shown how vector microbiota impact vector behavior and pathogen transmission, the effect vectors have on reservoir species microbiomes has been a less prominent focus. We were interested in the relationships between tick parasitism, …

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …

Adaptive Plasticity Of Coloration In Response To Environmental Change, Karissa Coffield

2023 Midwest Ecology & Evolution Conference

When rapid environmental changes occur, different selective forces can create phenotypic trade-offs in which a trait can provide fitness benefits or costs under different environmental conditions. Amphibians are particularly vulnerable to environmental change, and previous research has revealed that some species will plastically respond to variation in temperature and ultra-violet radiation (UVR) by altering their coloration. Divergent selection on coloration may change with elevation and climate induced shifts in temperature because high temperatures are likely to result in lighter color morphs but as elevation increases, UVR exposure increases leading to the prediction that darker color morphs will be more common. …

Rapid Assesment Of Aquatic Insect Diversity And Abundance Used To Evaluate The Quality Of Stream Restoration, Kaleb Stephen Kindoll

2023 Midwest Ecology & Evolution Conference

Stream and wetland restoration activities seek to improve the function of aquatic ecosystems. Measurement of the diversity and abundance of aquatic insects are commonly used to evaluate the success of restoration efforts, but these measurements are often very time consuming. In this study, we attempt to construct an efficient method that can be used to rapidly assess the diversity and abundance of aquatic insects as a measure of the quality of stream restoration. We suspended uniform sized pieces of cardboard paper coated with adhesive to trap insects in three different environments: one restored and two unrestored streams with similar characteristics. …

Movement, Behavior, And Trophic Ecology Of A Pelagic Predator Guild In The Eastern Tropical Pacific Ocean, Ryan Keith Logan

All HCAS Student Capstones, Theses, and Dissertations

Pelagic apex predators exert strong influences on ecological communities, and often support valuable commercial or recreational fisheries worldwide. Yet, due to their rarity and pelagic lifestyle, many species, such as billfishes, have proven particularly difficult to study at resolutions necessary to define dynamics of recovery from fishery interaction, physical interaction with environmental features and prey exploitation, and competitive interactions among other billfish predators. This leads to a paucity of knowledge on billfish ecology and habitat use, and hinders management efforts. With the ever-improving and miniaturization of technology and oceanographic datasets, the ability to define and quantify these interactions of fish …

Chronic Kidney Disease Promotes Cerebral Microhemorrhage Formation, Chuo Fang, Wei Ling Lau, Jiahong Sun, Rudy Chang, Adrian Vallejo, Donghy Lee, Jihua Liu, Han Liu, Yu-Han Hung, Yitong Zhao, Annlia Paganini-Hill, Rachita K. Sumbria, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background

Chronic kidney disease (CKD) is increasingly recognized as a stroke risk factor, but its exact relationship with cerebrovascular disease is not well-understood. We investigated the development of cerebral small vessel disease using in vivo and in vitro models of CKD.

Methods

CKD was produced in aged C57BL/6J mice using an adenine-induced tubulointerstitial nephritis model. We analyzed brain histology using Prussian blue staining to examine formation of cerebral microhemorrhage (CMH), the hemorrhagic component of small vessel disease and the neuropathological substrate of MRI-demonstrable cerebral microbleeds. In cell culture studies, we examined effects of serum from healthy or CKD patients and …

Comparison Of Dna Extraction Methods For Soft Tissue Samples, Steve Guzman, Nathaniel E. Hill, Mujtaba Shah, Jonathon Reynolds, Cole Farnsworth, Molly Henley, Alfred Amendolara, Laura Minor, John Dougherty Jr., John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

No abstract provided.