Animal Experimentation and Research Commons^™

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.

A Composition Of Phytonutrients For Glycemic And Weight Management, Yasuyo Urasaki

Annual Research Symposium

No abstract provided.

Update – Food & Drug Administration’S Animal Testing Mandate, Andrew N. Rowan

WellBeing News

Following the end of the Second World War, the World Medical Association developed new ethical guidelines regarding research involving human subjects. These guidelines included requirements to obtain informed consent from research subjects but also emphasized the importance of conducting animal research before engaging in human clinical trials and other human research. This principle was included in legislation mandating the FDA to require prior animal research before permitting human trials of new drugs. That mandate was recently eliminated by new US legislation cosponsored by Senators Cory Booker and Rand Paul. The FDA can now encourage non-animal methods and no longer has …

Differential Strain-Dependent Ovarian And Metabolic Responses In A Mouse Model Of Pcos, April K. Binder, Danielle L. Peecher, Amanda J. Qvigstad, Silvia D. Gutierrez, Jennifer Magaña, David B. Banks, Kenneth S. Korach

Biology Faculty Scholarship

Several mouse models have been developed to study polycystic ovarian syndrome (PCOS), a leading cause of infertility in women. Treatment of mice with dihydrotestosterone (DHT) for 90-days causes ovarian and metabolic phenotypes similar to women with PCOS. We used this 90-day DHT treatment paradigm to investigate the variable incidence and heterogeneity in two inbred mouse strains, NOD/ShiLtJ and 129S1/SvlmJ. NOD mice naturally develop type 1 diabetes, and recent meta-analysis found increased androgen excess and PCOS in women with type 1 diabetes. 129S1 mice are commonly used in genetic manipulations. Both NOD and 129S1 DHT treated mice had early vaginal opening, …

Loss-Of-Function KCa2.2 Mutations Abolish Channel Activity, Young-Woo Nam, Mohammad Asikur Rahman, Grace Yang, Razan Orfali, Meng Cui, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated potassium channels subtype 2 (K_Ca2.2, also called SK2) are operated exclusively by a Ca²⁺-calmodulin gating mechanism. Heterozygous genetic mutations of K_Ca2.2 channels have been associated with autosomal dominant neurodevelopmental disorders including cerebellar ataxia and tremor in humans and rodents. Taking advantage of these pathogenic mutations, we performed structure-function studies of the rat K_Ca2.2 channel. No measurable current was detected from HEK293 cells heterologously expressing these pathogenic K_Ca2.2 mutants. When co-expressed with the K_Ca2.2_WT channel, mutations of the pore-lining amino acid residues (I360M, Y362C, G363S …

Exploring The Potential Of Intranasally Administered Naturally Occurring Quercetin Loaded Into Polymeric Nanocapsules As A Novel Platform For The Treatment Of Anxiety, Shady Swidan, Khaled Younis Mahmoud, Nahla Ahmed Elhesaisy, Abdelrahman Rashed, Ebram Mikhael, Mahmoud Fadl, Mahmoud Elsadek, Merna Mohamed, Merna Mostafa, Mohamed Hassan, Omar Halema, Youssef Elnemer

Pharmacy

Anxiety is one of the most prevalent forms of psychopathology that afects millions worldwide. It gained more importance under the pandemic status that resulted in higher anxiety prevalence. Anxiolytic drugs such as benzodiazepines have an unfavorable risk/beneft ratio resulting in a shift toward active ingredients with better safety profle such as the naturally occurring quercetin (QRC). The delivery of QRC is hampered by its low water solubility and low bioavailability. The potential to enhance QRC delivery to the brain utilizing polymeric nanocapsules administered intranasally is investigated in the current study. Polymeric nanocapsules were prepared utilizing the nanoprecipitation technique. The best …

A Critical Look At Wild Pig Elimination: Myths And Facts, Kim M. Pepin, Travis L. Guerrant, Jeremiah L. Psiropoulos, Jeanine T. Neskey, John M. Tomeček, Michael J. Bodenchuk, Janean L. Romines

Human–Wildlife Interactions

Wild pigs (Sus scrofa) are abundant and widely distributed in the United States. They damage crops and pastures, predate livestock and sensitive species, impact ecosystem functions, and damage personal property. To address these issues, some states in the United States are seeking complete elimination. A frequently asked question by stakeholders is: “What portion of the population needs to be removed annually to reach elimination?” The number 70% is widely touted as the answer. There is little scientific evidence to support that this percent annual removal would be needed to achieve elimination, yet 70% has now become a standard …

An Automatic System To Evaluate Bait Station Visitation By Brown Treesnakes And Mongooses, Robert T. Sugihara, William C. Pitt, Are R. Berentsen, Francis L. Benevides Jr.

Human–Wildlife Interactions

Understanding the temporal, spatial, and behavioral patterns of the free-ranging target species in response to candidate baits and baiting strategies is important to ensure control success. This information can also assist in the development and deployment of feeding stations and can exclude non-target species while constituting effective bait delivery and control strategies for certain invasive animals, especially at environmentally sensitive sites. We used passive integrated transponder (PIT) tags in conjunction with very-high frequency radio-telemetry to remotely record bait station visitations and evaluate bait attractiveness in separate field research studies of brown treesnakes (Boiga irregularis) on Andersen Air Force …

A Growth Model For Arctica Islandica: The Performance Of Tanaka And The Temptation Of Von Bertalanffy—Can The Two Coexist?, John M. Klinck, Eric N. Powell, Kathleen M. Hemeon, Jillian R. Sower, Daniel R. Hennen

CCPO Publications

Organisms increase in size over time (age) due to excess assimilation over metabolic (respiration) energy demands. Most organisms reach a maximum size with increasing age as gain and loss balance. The von Bertalanffy length-at-age relationship, which is commonly used in fishery assessment calculations, imposes such a maximum size. However, some fished species, such as ocean quahogs, Arctica islandica, are long lived and continue to grow at old age. The Tanaka age-at-length relationship has continued growth at old age, but is rarely used in stock assessment models. A modified form of the von Bertalanffy model is presented, which mimics the …

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …

Effects Of Social Context On Salivary Cortisol And Attention In Tufted Capuchins (Cebus [Sapajus] Apella), Andrew Desana

Master’s Theses

Social context alters cognitive performance, but the mechanisms for this remain unclear. One possibility is that stressors associated with social contexts mediate changes in cognitive performance by influencing attention. We conducted two experiments to investigate how social context affects performance on an attention task in capuchin monkeys (Cebus [Sapajus] apella). We additionally validated and measured physiological stress through salivary cortisol. In experiment one, capuchins were exposed to three conditions where they were either isolated or paired with an affiliative or agonistic social partner separated by a barrier. In experiment two, subjects received affiliative and agonistic conditions without barriers to allow …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Investigating The Roles Of Platelet Bioenergetics In Hemostasis And Thrombosis, Kanakanagavalli Shravani Prakhya

Theses and Dissertations--Molecular and Cellular Biochemistry

Platelets use a series of energy-dependent processes to mediate hemostasis, yet it is unclear which metabolic fuels/pathways are critical for platelet function. Platelets are metabolically flexible, switching between glycolysis and oxidative phosphorylation (OxPhos) depending on oxygen tension and substrate availability. The deletion of GLUT1 and GLUT3 together revealed an essential role in platelet function and hemostasis. To study platelet bioenergetics, we used clot contraction. We created a sensitive and inexpensive method to simultaneously assess clot contraction kinetics to directly compare and define the effects of different treatments or genetic manipulations on platelet function.

Since the pharmacological inhibitors cannot be used …

Heat Shock Protein 90 (Hsp90) System In Health And Disease., Daniella Munezero

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cells rely on heat shock proteins (HSP) to facilitate and regulate the folding of the substrate proteins into their native state, and degradation if misfolding cannot be prevented. HSP90, a member of the HSP family, is a potential target for treatment of cancer and neurodegenerative diseases. Unfortunately, several clinical trials for cancer treatment have been discontinued due to cell toxicity accompanying HSP90 inhibition. HSP90 has four distinct but structurally similar paralogs. HSP90 inhibitors target all the paralogs despite increasing proof of functional differences among the paralogs. Understanding the in vivo function of HSP90 and the role played by each paralog …