Animal Experimentation and Research Commons^™

Animal Research For Alzheimer Disease: Failures Of Science And Ethics, John J. Pippin, Sarah E. Cavanaugh, Francesca Pistollato

Biomedicine and Animal Models in Research Collection

This chapter addresses the epidemiology and current understanding of AD as a scientific and societal challenge, reviews the uses and results of animal research in basic science and drug development, and discusses risk factors and funding. Important follow-up topics, including current and in-development, human-relevant approaches for replacement of the failed animal research paradigm, deserve comparable treatment and hence are not addressed here. The reader is referred to the list of recommended readings at the end of the chapter for further discussion of these topics.

Behavioral Research On Captive Animals: Scientific And Ethical Concerns, Kimberley Jayne, Adam See

Morality and Ethics of Animal Experimentation Collection

The first half of this chapter focuses exclusively on animals that are used in laboratory behavioral research to model wild behavior, what is typically involved, problems associated with this practice, and how behavioral research has revealed scientific problems in the animal model. The second half of this chapter then addresses the ethical questions of whether scientific curiosity of animal behavior in general provides any justification for carrying out this research in this first place, with specific focus on non-human primates (nhps).

Ethics, Efficacy, And Decision-Making In Animal Research, Lawrence A. Hansen, Kori Ann Kosberg

Morality and Ethics of Animal Experimentation Collection

Few would disagree with the ethical contention that if cruelty to animals is not wrong, then nothing is wrong. In fact, it is not only wrong, but in most states in the us, it is a crime, a felony no less. And yet, intentionally inflicting pain and suffering upon animals, which meets Webster’s definition of cruelty, is routinely countenanced when vivisection (from the Latin vivi, to be alive, and secare, to cut) is performed under license for biomedical research. Deciding to embrace, or reject, or limit animal research demands our best ethical judgment; and it is complicated by factual disputes …

Ethical And Scientific Pitfalls Concerning Laboratory Research With Non-Human Primates, And Possible Solutions, Constança Carvalho, Augusta Gaspar, Andrew Knight, Luís Vicente

Morality and Ethics of Animal Experimentation Collection

Basic and applied laboratory research, whenever intrusive or invasive, presents substantial ethical challenges for ethical committees, be it with human beings or with non-human animals. In this paper we discuss the use of non-human primates (NHPs), mostly as animal models, in laboratory based research. We examine the two ethical frameworks that support current legislation and guidelines: deontology and utilitarianism. While human based research is regulated under deontological principles, guidelines for laboratory animal research rely on utilitarianism. We argue that the utilitarian framework is inadequate for this purpose: on the one hand, it is almost impossible to accurately predict the benefits …

Identifying Dopamine Receptor Genes And Transcription Marbled Crayfish, Wolfgang Stein, Saisupritha Talasu

Faculty Publications – Biological Sciences

Modulatory transmitters are major contributors to nervous system plasticity and behavioral flexibility, they determine motivational states and are involved in psychiatric and neurological disorders. Neuromodulators act through a variety of distinct receptors and due to the diversity in receptor subtypes and distribution, a single neuromodulator can exert many different actions. A prerequisite to understand the ways modulators work is thus to identify which receptors are expressed in an animal.

I studied which Dopamine receptors are present in the Procambarus virginalis, a highly invasive species of all female genetic clones with high quality genome and transcriptomes. Their broad behavioral repertoire makes …

Hematologic Safety Of Chronic Brain-Penetrating Erythropoietin Dosing In App/Ps1 Mice, Jiahong Sun, Joshua Yang, Kathrine Whitman, Charlene Zhu, David H. Cribbs, Ruben J. Boado, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer's disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Changes In Expression Of The Autophagy-Related Genes Microtubule-Associated Protein 1 Light Chain 3Β And Autophagy Related 7 In Skeletal Muscle Of Fattening Japanese Black Cattle: A Pilot Study, Tomonori Nakanishi, Tadaaki Tokunaga, Takafumi Ishida, Ikuo Kobayashi, Yuta Katahama, Azusa Yano, Laurie Erickson, Satoshi Kawahara

Hebrew Theological College Publications and Research

Objective

Autophagy is a bulk degradation system for intracellular proteins which contributes to skeletal muscle homeostasis, according to previous studies in humans and rodents. However, there is a lack of information on the physiological role of autophagy in the skeletal muscle of meat animals. This study was planned as a pilot study to investigate changes in expression of two major autophagy-related genes, microtubule-associated protein 1 light chain 3β (MAP1LC3B) and autophagy related 7 (ATG7) in fattening beef cattle, and to compare them with skeletal muscle growth.

Methods

Six castrated Japanese Black cattle (initial body weight: 503±20 kg) were enrolled in …

Optimization Of Primary Cilia Detection In Musculoskeletal Tissue, Ragen Engel

Williams Honors College, Honors Research Projects

The objective of this research project was to optimize a laboratory technique for visualizing primary cilia in musculoskeletal tissue of young swine, specifically the growth plate of long bones. This was accomplished through varying fixation procedures, antigen retrieval methods, antibody concentrations, and incubation times. By varying these parameters, a reproducible procedure was developed to examine the primary cilia in multiple tissues including ligament, fascia, and growth plate. This experiment introduced variances in fixation methods, with methanol or formalin. Paraffin and frozen embedding techniques were also varied for comparison with regards to cilia visualization. Results from the acetylated alpha tubulin (aTUB) …

Development Of A Functional Testing Platform For The Sensory Segment Of The Neuromuscular Reflex Arc, Alisha Colon

Electronic Theses and Dissertations

Investigations of human biology and disease have been hindered by the use of animal models. The information obtained from such studies often results in clinically irrelevant results and drug trial failures. Additionally, several governing bodies have been formulating legislation to move away from animal models and toward more ethical and efficient testing platforms for drug discovery and cosmetic research. As an answer to these issues, "body-on-a-chip" systems have been a rapidly developing field which easily recapitulates in vivo functionality, providing a more relevant, repeatable, and ethical testing platform to better predict biology. These systems can be used as human-based testing …

Population Health Of Spotted Salamanders (Ambystoma Maculatum) In Created Vernal Pools: An Integrative Approach, Alice R. Millikin

Graduate Theses, Dissertations, and Problem Reports (ETD)

Habitat creation is an important tool for conservation to counteract habitat loss and degradation. Vernal pools are susceptible to destruction due to limited detection, protection, and regulation. These wetlands provide fishless breeding habitat for many amphibian species including spotted salamanders (Ambystoma maculatum) in eastern North America. Determining whether created vernal pool habitat is successful is often determined by demographic data of colonizing populations. I suggest that hormone levels, population genetics, and disease prevalence can improve our understanding of population health in created habitat. The goal of this dissertation was to assess the health of spotted salamander larvae in …

Effect Of Group Size On The Activity Budget Of Two Captive Chimpanzees (Pan Troglodytes), Kaeley Sullins

All Master's Theses

Captive facilities housing chimpanzees are required to provide adequate care and provisions such as dietary, social, and environmental enrichment to promote the psychological well-being of the apes in their care. Chimpanzees are social creatures and changes in groups as well as relocation to a facility with new social partners, can impact each individual chimpanzee’s welfare. By tracking each chimpanzee’s activity budgets, managers can assess welfare and make improvements or adjustments if necessary. I looked at the activity budgets of two captive chimpanzees after the death of a group member and the two chimpanzees’ subsequent relocation to a novel, more socially …

Cold Tolerance, Temperature Mediated Discontinuous Gas Exchange, And Emergence Of The Blue Orchard Mason Bee (Osmia Lignaria), Logan Kral

All Master's Theses

The relationship between low temperatures, emergence and supercooling point of Osmia lignaria were the subject of this study. One hundred sixty-eight bees were subjected to 5 pre-wintering temperature treatments (two constant temperature controls - 22^oC, 14^oC, one of which with and one without a 12h photoperiod, and three 12h:12h thermoperiod treatments – 14:10^oC, 14:5^oC, and 14:0^oC) and were then evaluated in terms of emergence time and post-emergence vigor. An additional 70 bees were tested for metabolic rate and discontinuous gas exchange in response to test temperature conditions. An additional sample …

Seal And Polar Bear Behavioral Response To An Icebreaker Vessel In Northwest Greenland, Kate Lomac-Macnair, José Pedro Andrade, Eduardo Esteves

Human–Wildlife Interactions

Icebreaker vessels are important scientific tools, enabling access and research within the polar regions of the world, including the High Arctic. These vessels have the potential to overlap with marine mammal habitats in infrequently studied areas. Marine mammal behavioral responses to icebreaker vessel presence and distance at which responses occur are not well documented or understood. During the Petermann 2015 Expedition on the icebreaker Oden, seal and polar bear (Ursus maritimus) data were collected in Petermann Fjord (Northwest Greenland), the adjacent Nares Strait region, and transit to and from Thule, Greenland over 31 days (July 30 to …

Probability Discounting Of Lewis And Fischer 344 Rats: Strain Comparisons At Baseline And Following Acute Administration Of D-Amphetamine, Jenny E. Ozga

Graduate Theses, Dissertations, and Problem Reports (ETD)

Risky choice can be defined as choice for a larger, uncertain reinforcer over a smaller, certain reinforcer when choosing the smaller alternative maximizes reinforcement. Risky choice is studied using various procedures in the animal laboratory; one such procedure is called probability discounting. There are many variables that contribute to risky decision-making, including biological and pharmacological determinants. The present study assessed both of these variables by evaluating dose-response effects of d-amphetamine on risky choice of Lewis (LEW) and Fischer 344 (F344) rats. The probability-discounting procedure included discrete-trials choices between one food pellet delivered 100% of the time and three food …

Behavioral Assessment Of Social Structure And Guest Provisioning Program Participation Of Zoo-Housed Giraffes (Giraffa Camelopardalis) Under Varying Spatial Availability., Fatima Ramis

UNF Graduate Theses and Dissertations

Close encounters with animals are considered integral for visitors and are trademark components of traditional educational engagement in zoological parks. As capacity for up-close encounters continue to increase with a simultaneous development in the field of animal welfare science, behavioral assessments on the role of common close encounters is timely. Giraffes (Giraffa camelopardalis) visitor feeding programs are established in approximately 57% of institutions accredited by Association of Zoos and Aquariums. Due to successful breeding and capacity building for zoological giraffe populations, this percentage will likely continue to increase. There is a great deal of variation in the environmental …

Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra

Theses and Dissertations

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT_2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT_2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT_2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT_2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …

Microplastics In Full View: Birds As Bioindicators Of Malta's Coastal Ecosystem Health, Dalton Brauer

Masters Theses, 2010-2019

Plastic pollution has recently become a widely studied topic, yet research on microplastics has remained lacking for specific geographic regions. Microplastics are small plastics resulting from degradation or the dumping of raw material and can lead to deleterious impacts on the coastal marine environment and its organisms. To assess Malta’s coastal environmental health, water birds (inshore, offshore and pelagic species) were used as bioindicators by assessing the presence and abundance of plastic within their stomach contents. The project hoped to fill some of the current gaps in knowledge on microplastics within Malta by creating a working baseline, as well as …

Study Of Three Potential Variables That May Impact The Maximum Shear Force And Shear Variation During The Growth And Transport Of Mixed Sex Broilers Grown In Commercial Poultry Houses, Mark Christie

Graduate Theses and Dissertations

Temperature conditions during the transportation to the processing facility of commercial broilers have a direct impact on the meat texture, specifically maximum shear force and shear variation of cooked breast meat. Analysis of a calendar year of flock data (N=346), reveals that the largest impact of transport conditions, specifically temperature, is on the standard deviation of the flocks range of cooked shear values. The optimal transport temperature that yields broiler breast meat with average flock minimum shear and standard deviation values is approximately 60°F. The shear values for flocks at or near 60°F are on average 1 kg less than …

Optimizing Methods To Determine Metabolizable Energy Values Of Feed Ingredients For Broilers, Skyler P. West

Graduate Theses and Dissertations

Determination of metabolizable energy (ME) and amino acid (AA) digestibility values of single feed indigents continues to be two of the most important aspects for successful least-cost poultry feed formulation. It would be advantageous if a common diet type could be utilized to determine both ME and AA digestibility values of feed ingredients within a single assay. Two experiments were conducted to evaluate the effect of basal diet type and excreta collection method on the ME value of single feed ingredients determined in broiler chicks using the regression method. In experiment 1, the objective was to investigate the influence of …

Efficacy Of Natural Compounds With Novel Carrier Systems For Controlling Campylobacter Jejuni In Post-Harvest Poultry, Sandip Shrestha

Graduate Theses and Dissertations

Campylobacter jejuni, a leading cause of bacterial gastroenteritis worldwide, is strongly associated with the consumption and/or mishandling of raw contaminated poultry products. Thus, interventions aiming to reduce C. jejuni counts on poultry products could greatly reduce the incidence of human campylobacteriosis. In the first study, the efficacy of a generally recongnized as safe (GRAS) compound, carvacrol (CR; derived from oregano oil), as an antimicrobial wash treatment to reduce C. jejuni on chicken skin was evaluated. Three delivery systems of CR: suspension, emulsion and nanoemulsion were used. C. jejuni counts were reduced up to 4 log10 cfu/sample by 2% dose of …

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …

No Evidence For Kin Protection In The Expression Of Sickness Behaviors In House Mice, Patricia C. Lopes, Per Block, Alice Pontiggia, Anna K. Lindholm, Barbara König

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When infected, animals change their behaviors in several ways, including by decreasing their activity, their food and water intake, and their interest in social interactions. These behavioral alterations are collectively called sickness behaviors and, for several decades, the main hypotheses put forward to explain this phenomenon were that engaging in sickness behaviors facilitated the fever response and improved the likelihood of host survival. However, a new hypothesis was recently proposed suggesting that engaging in sickness behaviors may serve to protect kin. We tested this kin protection hypothesis by combining a field and a laboratory experiment in house mice. In both …

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study is to …

Diffusion Through The Ex Vivo Vitreal Body – Bovine, Porcine, And Ovine Models Are Poor Surrogates For The Human Vitreous, Sara Shafaie, Victoria Hutter, Marc B. Brown, Michael T. Cook, David Y.S. Chau

Pharmacology and Animal Models in Research Collection

The human vitreous humour is a complex gel structure whose composition and physical properties can vary considerably from person to person and also change with age. To date, the viscoelastic properties of the human vitreous gel has not been thoroughly investigated and despite many years of intensive research, an ideal vitreous substitute remains a challenge. Understanding the physical structure and properties of the vitreous is of fundamental and therapeutic interest, providing a clear insight into diffusion and transport of administered ophthalmic drug molecules into the vitreous. A number of mammalian surrogates, mainly bovine, porcine and ovine vitreous humours have been …

Factors Affecting Gastropod Larval Development And Performance: A Systematic Review, Maria Rosa, Dianna K. Padilla, David Charifson, Alyssa Liguori, Mica Mccarty-Glenn, Allison Rugila

Biology Faculty Publications

The goal of this article was to use a systematic review of studies on the larval stages of gastropods reared to metamorphosis to determine whether there are general patterns for the effects of temperature, rearing density, and food availability on larval development and performance among species, major taxa, and modes of development. Most studies did not include sufficient metadata to be included in many of the analyses. For all analyses, there were differences among major groups of taxa in terms of response to the considered variables. Increased temperature was frequently correlated with decreased development time and increased growth but often …

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …

Role Of Intrinsic Disorder In Animal Desiccation Tolerance, Brett Janis, Clinton Belott, Michael Menze

Faculty and Staff Scholarship

This review compares the molecular strategies employed by anhydrobiotic invertebrates to survive extreme water stress. Intrinsically disordered proteins (IDPs) play a central role in desiccation tolerance in all species investigated. Various hypotheses about the functions of anhydrobiosisrelated intrinsically disordered (ARID) proteins, including late embryogenesis abundant (LEA) and tardigrade-specific intrinsically disordered proteins, were evaluated by broad sequence characterization. A surprisingly wide range in sequence characteristics including hydropathy and the frequency and distribution of charges was discovered. Interestingly, two clusters of similar proteins were found that potentially correlate with distinct functions. This may indicate two broad groups of ARID proteins, composed of …

Uplc-Ms/Ms Analysis Of Dextromethorphan-O-Demethylation Kinetics In Rat Brain Microsomes, Barent N. Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Formation of dextrorphan (DXT) from dextromethorphan (DXM) has been widely used to assess cytochrome P450 2D (CYP2D) activity. Additionally, the kinetics of CYP2D activity have been well characterized in the liver microsomes. However, studies in brain microsomes are limited due to the lower microsomal content and abundance of CYP2D in the brain relative to the liver. In the present study, we developed a micro-scale enzymatic incubation method, coupled with a sensitive UPLC-MS/MS assay for the quantitation of the rate of DXT formation from DXM in brain microsomes. Rat brain microsomes were incubated with different concentrations of DXM for various times. …

Targeting Neuropeptides To Bone Fractures For Accelerated Healing, Nicholas A. Young, Jeffery J. Nielsen, Philip S. Low

The Summer Undergraduate Research Fellowship (SURF) Symposium

In patients over the age of 65 especially, bone fractures represent a significant disease burden. Non-invasive drug therapies are not available for bone fractures which represents a problem for this population. Vasoactive intestinal peptide (VIP) and Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), two neuromodulator peptides in the glucagon superfamily, have demonstrated positive regulation of osteoblast proliferation and activity. Using acidic oligopeptides, we have developed ligands that target to and accumulate at fracture sites. These targeting ligands can be synthesized in sequence with bone anabolic peptides to minimize off target effects and increase potency at the fracture site to create safer and …