Animal Experimentation and Research Commons^™

Validation Of A Novel Trpm8 Knockout Mouse Model, Bilan Mohamed

Thinking Matters Symposium

Recent studies suggest that the use of thermoregulatory treatments that affect brown fat may help curb obesity. However it is unknown how these treatments may affect bone homeostasis. Our work has focused on the transient receptor potential melastatin (TRPM8) protein, which is responsible for detecting colder temperatures in sensory neurons. Previous work within the Motyl laboratory has found that Trpm8 plays a role in bone acquisition. Mice with a global deletion of the Trpm8 gene have reduced trabecular bone volume fraction due to reduced bone formation by osteoblasts. However, it is unclear whether sensory neuron or osteoblast-mediated expression of Trpm8 …

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

Seasonal Plumage Condition Variation And The Thermal Value Of The Feather Coats Of House Sparrows (Passer Domesticus), Jordana Mf Graveley, Margaret Rubega, Kevin R. Burgio

Honors Scholar Theses

Feathers are critical to how birds thermoregulate, and thus their total energy balance. The feather coat insulates birds by trapping air next to the skin and acting as a physical barrier to heat loss. Despite previous work studying thermal balance in birds, relatively few studies have focused on the thermal contribution of the feather coat alone; most studies have focused on physiological and behavioral responses. Moreover, to our knowledge, no studies have directly measured the effect of feather wear through the annual cycle on the thermal performance of the feather coat. To address this, we used a thermal camera to …

Optimization Of Grow-Out Of Bouldering Coral Microfragments: Land Vs. Offshore Nursery, Ashlee A. Steinberg

All HCAS Student Capstones, Theses, and Dissertations

Corals along the Florida Reef Tract and the wider Caribbean have been declining for decades. Low densities of adult colonies hinder the ability of corals to replenish themselves through sexual reproduction, thus reef managers are focusing on restoration actions that increase coral biomass. Microfragmentation is a way to quickly increase the biomass of bouldering corals by cutting the coral into small pieces which forces the coral to allocate its resources away from reproduction and back into growth, increasing its growth rate. This study assessed the optimal location for grow-out (land vs. offshore nursery) and its synergy with size of fragment …

Trials And Tribulations Of Humanizing Mice For Cancer Research, Brittney Ruedlinger, Steven Warsof, Eric Feliberti, Mary Beth Hughes, Ayobami ‘Edwin’ Oshin, Chunqi Jiang, Brittany P. Lassiter, Siqi Guo, Stephen J. Beebe

The Graduate School Posters

Cancers are aggressive, evasive, and ruthless killers, claiming millions of lives every year. Cancers are heterogeneous and there is often no single, clearly defined problem as they harness and manipulate a multitude of fundamental mechanisms at the very essence of life. To investigate these mechanisms and vet potential interventive therapies, humanized mice offer a unique model as a prelude to the use of nanosecond pulse stimulation (NPS), a pulse power technology applying nanosecond duration, high electric field pulses, to ablate human tumors. Immunodeficient mouse strains, NSG and NSG-SGM3, were engrafted with human immune cells and human tumors, which would allow …

Morph- And Sex-Specific Differences In Corticosterone Of The Arizona Tiger Salamander (Ambystoma Mavortium Nebulosum), Megan Zerger

Scholars Week

Life history morph, sex, and body condition are traits that may influence stress within salamander populations because of differences in physiology and environmental conditions. Given widespread declines and the effects chronic stress can have on amphibian health, it is important to understand within-population drivers of stress and how population level variation may influence population viability. Thus, the objective of our study was to assess how corticosterone varies within the Arizona tiger salamander (Ambystoma mavortium nebulosum) population at the Mexican Cut Nature Preserve. We used a non-invasive skin swabbing method to collect baseline and elevated corticosterone from paedomorph (aquatic …

Anti-Inflammatory Effects Of Α7-Nicotinic Ach Receptors Are Exerted Through Interactions With Adenylyl Cyclase-6, Simeng Zhu, Shiqian Huang, Guofang Xia, Jin Wu, Yan Shen, Ying Wang, Rennolds S. Ostrom, Ailian Du, Chengxing Shen, Congfeng Xu

Pharmacy Faculty Articles and Research

Background and purpose

Alpha 7 nicotinic acetylcholine receptors (CHRNA7) suppress inflammation through diverse pathways in immune cells, so is potentially involved in a number of inflammatory diseases. However, the detailed mechanisms underlying CHRNA7’s anti‐inflammatory effects remain elusive.

Experimental approach

The anti‐inflammatory effects of CHRNA7 agonists in both murine macrophages (RAW 264.7) and bone marrow‐derived macrophages (BMDM) stimulated with LPS were examined. The role of adenylyl cyclase 6 (AC6) in Toll‐like Receptor 4 (TLR4) degradation was explored via overexpression and knockdown. A mouse model of chronic obstructive pulmonary disease was used to confirm key findings.

Results

Anti‐inflammatory effects of CHRNA7 were …

A Zugunruhe Data Collection System Using Passive Infrared Sensors, Ryan Terry, Luis E. Ramirez, Carol Carrera, Abigail Kimmitt, Kira Delmore, Ana Goulart

Pursue: Undergraduate Research Journal

When engineers and biologists work together, there is a lot to learn on both sides. For instance, our work introduced us to zugunruhe, which is a German word that means “unrest”. It is used in the context of migratory birds, as they become restless at night, inside their cages, during their migratory period. When does zugunruhe start? It usually starts when the weather becomes cold and the days shorter, but it varies for different bird species. Moreover, global warming has caused changes in zungunruhe’s timing, which made it even harder to predict. Another question is about genetics: is …

Dirofilaria Immitis Prevalence In Canis Latrans In Kentucky, Melanie Ann Brandon

Murray State Theses and Dissertations

Dirofilaria immitis (canine heartworm) was found in forty-two (42) of the two hundred seventy-five (275) Canis latrans (coyote) necropsied in the state of Kentucky from November 27, 2019 through March 3, 2021. Thirty-five (35) of the positive cases were from western Kentucky region with the other seven spread across the state. With this group of coyotes, one hundred fifty-eight (158) were male and the other one hundred six-teen (116) were female. The estimated age ranged from a pup to senior dogs. A little over forty percent of the dogs were obtained through coyote/predator tournaments; the remaining were acquired from pest …

Effects Of Wastewater Effluent On Fish Fin Morphology Of Larval Fathead Minnows (Pimephales Promelas) And Swimming Performance Of Smallmouth Buffalo (Ictiobus Bubalus), Seth Michael Bogue

Masters Theses

The Sangamon River flows across central Illinois and is mostly free flowing except in the city of Decatur where it is impounded to form Lake Decatur. The Sanitary District of Decatur (SDD) is located approximately three miles downstream of the Lake Decatur dam. For a significant portion of the year, the stretch of the Sangamon River downstream of SDD is dominated by effluent due to limited discharge from the Lake Decatur dam. This has resulted in heavy nutrient loading, most notably phosphorus, and elevated levels of nickel and other compounds in the downstream section of the river. Smallmouth buffalo ( …

The Human—Long-Tailed Macaque (Macaca Fascicularis) Interface At Don Chao Poo Forest, Phana, Thailand, Ashton M. Asbury

All Master's Theses

When provisioned food is available, human-macaque coexistence may result in altered macaque behaviors and the possibility of bidirectional disease transmission through interspecies contact. Don Chao Poo forest in Thailand is a conservation site where ~ 1,000 long-tailed macaques (Macaca fascicularis) live and interact with people, which includes being provisioned by volunteers and visitors. Phana macaques are habituated to human presence as a result of their frequent interactions with people. I tested whether 1) men and women are equally likely to have contact interactions with macaques, 2) adult and immature macaques are equally likely to have contact interactions with …

Distinct Cellular Profiles Of Hif1a And Vegf Mrna Localization In Microglia, Astrocytes And Neurons During A Period Of Vascular Maturation In The Auditory Brainstem Of Neonate Rats, Daphne Chang, Quetanya Brown, Grace Tsui, Ye He, Jia Liu, Lingyan Shi, Adrián Rodríguez-Contreras

Advanced Science Research Center

Defining the relationship between vascular development and the expression of hypoxia-inducible factors (Hifs) and vascular endothelial growth factor (Vegf) in the auditory brainstem is important to understand how tissue hypoxia caused by oxygen shortage contributes to sensory deficits in neonates. In this study, we used histology, molecular labeling, confocal microscopy and 3D image processing methods to test the hypothesis that significant maturation of the vascular bed in the medial nucleus of the trapezoid body (MNTB) occurs during the postnatal period that precedes hearing onset. Isolectin-B4 histochemistry experiments suggested that the MNTB vasculature becomes more elaborate between …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Vulnerable And Resilient Phenotypes In A Mouse Model Of Anorexia Nervosa, Jeff A. Beeler, Devry Mourra, Roseanna M. Zanca, Abigail Kalmbach, Celia Gellman, Benjamin Y. Klein, Rebecca Ravenelle, Peter Serrano, Holly Moore, Stephen Rayport, Susana Mingote, Nesha Burghard

Advanced Science Research Center

Background

Increased physical activity is a common feature of anorexia nervosa (AN). Although high activity levels are associated with greater risk of developing AN, particularly when combined with dieting, most individuals who diet and exercise maintain a healthy body weight. It is unclear why some individuals develop AN while most do not. A rodent model of resilience and vulnerability to AN would be valuable to research. Dopamine, which is believed to play a crucial role in AN, regulates both reward and activity and may modulate vulnerability.

Methods

Adolescent and young adult female C57BL/6N mice were tested in the activity-based anorexia …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports (ETD)

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Molecular Mechanisms Regulating Optic Fissure Fusion During Zebrafish Eye Development, Megan Weaver

Theses and Dissertations--Biology

Vertebrate retinal development requires timely and precise fusion of the optic fissure. Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed optic fissure fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a^-/- embryos fail to accumulate F-actin in the optic fissure prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a^-/- embryos. When examining the connection …

Cellular Bioenergetics Regulates Cell Proliferation During Mammalian Regeneration, Sandeep Saxena

Theses and Dissertations--Biology

Mammalian system consists of stress-sensing molecules that regulates their cellular response against damage, injury and oncogenic stress. During vertebrate regeneration, cells responding to injury re-enter the cell cycle and proliferate to form new tissue. Cell cycle re-entry or arrest is at least partly regulated by cellular senescence which negatively impacts the proliferative pool of cells during regeneration. What remains unclear is whether cells in regenerating systems possess an increased propensity to proliferate and are refractory to signals that induce senescence. My thesis work has focused on how fibroblasts from the ear pinna differentially regulate healing in highly regenerative mammals (e.g., …

Identifying Genes Downstream Of Mef2 That Influence Ethanol Sedation In Drosophila Melanogaster, Ananya Talikoti

Theses and Dissertations

Alcohol use disorder is a global public health issue that affects millions across the world. It can result in negative physical and mental health outcomes, and currently treatment options are limited and rates of relapse are high. Identifying genes that affect aspects of ethanol behaviors in model organisms, such as Drosophila melanogaster, can serve to eventually develop more robust therapeutic interventions for those experiencing alcohol dependence. Previous studies have identified a relationship between a person's initial sensitivity to alcohol and their abuse potential for the drug in later life. Therefore, we can study sedation behaviors in Drosophila melanogaster to …

There’S More Than One Way To Beat The Heat: What Anal Probes Reveal About Thermal Responses In Neotropical Beetles (Coleoptera: Cerambycidae)., Emilie I. Dion

Dissertations and Theses

Increasing global temperatures have been linked to shifts in the distributions and preferred microhabitats of terrestrial species. This trend is predicted to impact tropical forest insects, which may already be exposed to conditions that bring them close to their thermal maxima. Tropical microhabitats are linked to vertical stratification, because the canopy is hotter, winder, and less humid than the ground. In ectothermic organisms, such as beetles, thermoregulation is dependent on morphological and behavioral traits. This study investigates woodboring cerambycid beetles, to determine how behavioral thermoregulation through microhabitat selection (vertical stratification) is correlated to morphological attributes (color lightness, size, and pubescence) …

A New Mathematical Theory For The Dynamics Of Large Tumor Populations, A Potential Mechanism For Cancer Dormancy & Recurrence And Experimental Observation Of Melanoma Progression In Zebrafish, Adeyinka A. Lesi

Dissertations and Theses

Cancer, a family of over a hundred disease varieties, results in 600,000 deaths in the U.S. alone. Yet, improvements in imaging technology to detect disease earlier, pharmaceutical developments to shrink or eliminate tumors, and modeling of biological interactions to guide treatment have prevented millions of deaths. Cancer patients with initially similar disease can experience vastly different outcomes, including sustained recovery, refractory disease or, remarkably, recurrence years after apparently successful treatment. The current understanding of such recurrences is that they depend on the random occurrence of critical mutations. Clearly, these biological changes appear to be sufficient for recurrence, but are they …