Animal Experimentation and Research Commons^™

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 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. …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Impact Forces And Patterns Of Axonal Injury Differ Between Two Models Of Tbi, Edward Lai, David M Devilbiss

Rowan-Virtua Research Day

Traumatic brain injury (TBI) affects approximately 3.8 million Americans a year and results in complex neuropathological and neurocognitive sequelae. Animal models of TBI attempt to replicate the impact forces and pathology of injury in humans. However, in these models, the forces generated at the time of impact are poorly understood. Nonetheless, a variety of shear and strain forces generated at the time of impact can produce diffuse axonal injury. Injury to axons and neurons across a variety of brain regions resulting from axonal injury underlies the cognitive and behavioral impairments observed after TBI. Three critical brain regions, the corpus callosum …

Blood–Brain Barrier Breakdown And Astrocyte Reactivity Evident In The Absence Of Behavioral Changes After Repeated Traumatic Brain Injury, Celeste Dunn, Nasya Sturdivant, Sara Venier, Syed Ali, Jeffery Wolchok, Kartik Balachandran

Biomedical Engineering Faculty Publications and Presentations

Repeated traumatic brain injuries (TBIs) cause debilitating effects. Without understanding the acute effects of repeated TBIs, treatment options to halt further degeneration and damage cannot be developed. This study sought to examine the acute effects of blood–brain barrier (BBB) dysfunction, edema, inflammation and behavioral changes after either a single or double TBI using a C57BL/6 mouse model. We examined the effects of one or two TBIs, of either a mild or moderate severity. Double injuries were spaced 7 days apart, and all analysis was performed 24 h post-injury. To examine edema and inflammation, protein levels of glial fibrillary acidic protein …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

Graduate Theses/Dissertations

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

Safety Of Silver Oxide Coated Biomaterials In Mice, Michael Klug, Darien L. Seidman, Rahyan Mahmoud, Destiny Morot, Lei Yu, Jeffrey D Hettinger, Renee M Demarest

Rowan-Virtua Research Day

It has been demonstrated that silver oxide coatings designed by our collaborators are able to prevent E. coli and P. aeruginosa attachment to biomaterials in vivo. These findings demonstrate that such coatings show promise in preventing the development of biofilm on biodevices. However, it is unknown if the use of silver oxide in this fashion is toxic in vivo. The goal of this project was to determine whether our silver oxide coatings are safe to use in vivo. To assess the toxicity of our silver oxide formula, mice were implanted with either silver oxide coated titanium discs or uncoated titanium …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations and Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

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 …

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 …

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 …

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) …

The Best Predictions In Experimental Biology Are Critical And Persuasive, Douglas S. Fudge, Andy J. Turko

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

A powerful way to evaluate scientific explanations (hypotheses) is to test the predictions that they make. In this way, predictions serve as an important bridge between abstract hypotheses and concrete experiments. Experimental biologists, however, generally receive little guidance on how to generate quality predictions. Here, we identify two important components of good predictions – criticality and persuasiveness – which relate to the ability of a prediction (and the experiment it implies) to disprove a hypothesis or to convince a skeptic that the hypothesis has merit. Using a detailed example, we demonstrate how striving for predictions that are both critical and …

Microglia-Neuron Interactions In A Mouse Model Of Low Grade Neuroepithelial Tumors, Veolette Hanna

Honors Scholar Theses

Microglia are the macrophages of the brain and spinal cord, playing an important role in the immune response to disease states of the nervous system. This study conducts an investigation on the activity of microglia in response to low grade neuroepithelial tumors. Using mouse models and microglial markers, a qualitative and quantitative analysis of microglia activation, migration, and invasion within the brain cortex during early stages of tumor development was conducted. It was found that the presence of a low grade neuroepithelial tumor in the cortex of one hemisphere of the brain causes significant microglia activation in comparison to the …

Ctrp3 And Alcoholic Liver Disease In Female Mice, Callie Root

Undergraduate Honors Theses

C1q TNF Related Protein 3 (CTRP3), is a cytokine that is primarily secreted from adipose tissue, which classifies it as an adipokine. Our previous research has shown that CTRP3 prevents alcoholic fatty liver disease (ALD) in male mice. However, even when accounting for confounding factors such as absolute and relative alcohol intake, females are more sensitive to the effects of consumption compared to male mice. Therefore, the goal of this project was to determine whether CTRP3 prevented ALD in female mice. Methods: Female wild type (WT) and female CTRP3 transgenic over expressing (Tg) mice were fed an ethanol containing liquid …

Focal Augmentation Of Somatostatin Interneuron Function And Subsequent Circuit Effects In Developmentally Malformed, Epileptogenic Cortex, Nicole Ekanem

Theses and Dissertations

Drug-resistant epilepsy (DRE) is a common clinical sequela of developmental cortical malformations such as polymicrogyria. Unfortunately, much remains unknown about the aberrant GABA-mediated circuit alterations that underlie DRE's onset and persistence in this context. To address this knowledge gap, we utilized the transcranial freeze lesion model in optogenetic mice lines (Somatostatin (SST)-Cre or Parvalbumin (PV)-Cre x floxed channelrhodopsin-2) to dissect features of the SST, PV, and pyramidal neuron microcircuit that are potentially associated with DRE. Investigations took place within developmental microgyria’s known pathological substrate, the adjoined and epileptogenic paramicrogyral region (PMR). As well, microcircuit relationships within the previously unexplored range …

Non-Invasive Method For Leptin Supplementation In Zebrafish (Danio Rerio), Regan Mcnamara

Williams Honors College, Honors Research Projects

I tested the hypothesis that recombinant leptin protein can be introduced to zebrafish in vivo through non-invasive soaking in a solution containing the protein. One way to study various molecules’ effects in vivo is through intraperitoneal or intracerebroventricular injections during the embryonic or larval stage, which is invasive, difficult to administer, and can have a high mortality rate. 48 hours post fertilization (hpf) zebrafish were soaked in a His-tagged recombinant leptin protein solution at 10 nM and 100 nM concentrations (produced by Genscript). After soaking, zebrafish larvae were washed extensively to remove all recombinant protein on their exterior before homogenization. …

Cyclin C Regulated Oxidative Stress Responsive Transcriptome In Mus Musculus Embryonic Fibroblasts, David C Stieg, Kai-Ti Chang, Katrina F Cooper, Randy Strich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The transcriptional changes that occur in response to oxidative stress help direct the decision to maintain cell viability or enter a cell death pathway. Cyclin C-Cdk8 is a conserved kinase that associates with the RNA polymerase II Mediator complex that stimulates or represses transcription depending on the locus. In response to oxidative stress, cyclin C, but not Cdk8, displays partial translocation into the cytoplasm. These findings open the possibility that cyclin C relocalization is a regulatory mechanism governing oxidative stress-induced transcriptional changes. In the present study, the cyclin C-dependent transcriptome was determined and compared to transcriptional changes occurring in oxidatively …

Jet Lag: What’S Light Got To Do With It?, Melissa Richardson

Adventist Human-Subject Researchers Association

Jet lag results in memory loss and sleepiness. Current treatments for jet lag focus on symptoms and not the cause of jet lag; disrupted light environment. This study in mice, uncovered mechanisms of how light regulates jet lag recovery and memory. This work informs our future studies in humans.

The Effects Of Salinity On Zootechnical Performance Of Spotted Seatrout (Cynoscion Nebulosus) In Recirculating Aquaculture Systems, Eric Gigli

Master's Theses

The spotted seatrout (Cynoscion nebulosus) is a euryhaline finfish candidate for marine aquaculture in the northern Gulf of Mexico. Aquaculture of this species currently uses salinities of 25 psu or greater making production challenging in areas where high salinity water is not available. This study aimed to document the effects of salinity on zootechnical performance of spotted seatrout embryos, early larvae, and juveniles in recirculating aquaculture systems to assist with the development of protocols for low salinity culture.

Embryos obtained from a volitional spawn at 29 psu were incubated at three salinities (12.5, 18.75, or 25 psu) until …

Animal Experimentation: Working Towards A Paradigm Change, Kathrin Herrmann (Ed.), Kimberley Jayne (Ed.)

eBooks

Animal experimentation has been one of the most controversial areas of animal use, mainly due to the intentional harms inflicted upon animals for the sake of hoped-for benefits in humans. Despite this rationale for continued animal experimentation, shortcomings of this practice have become increasingly more apparent and well-documented. However, these limitations are not yet widely known or appreciated, and there is a danger that they may simply be ignored. The 51 experts who have contributed to Animal Experimentation: Working Towards a Paradigm Change critically review current animal use in science, present new and innovative non-animal approaches to address urgent scientific …

Spatial And Temporal Variability In Post-Larval Yellow Perch Density, Steve Hauschildt

Biology Graduate Theses

Yellow Perch Perca flavescens are important as forage for other species and for sport fishing in many northern lakes. However, estimating post-larval Yellow Perch populations can be difficult because of many environmental factors that cause unexplained variation. The objective of this study was to help reduce unexplained variation by determining a post-larval Yellow Perch population density estimate on Blackduck Lake, MN, provide guidance to help determine the number of trawls required for trawling-based recruitment indices to achieve varying levels of precision, and test for the effects of wind speed and direction on post-larval Yellow Perch spatial variability. This study estimated …

Growth Of Pelagic Age-0 Yellow Perch In Relation To Hatch Dates And Water Temperature In North-Central Minnesota Lakes, Ethan Karppinen

Biology Graduate Theses

Exposure to consistent water warming rates and access to abundant populations of edible sized zooplankton affects growth and increases the probability of survival for newly hatched Yellow Perch Perca flavescens. Seven lakes with varying physical characteristics were selected in north-central Minnesota to study abiotic (water temperature) and biotic (zooplankton community and fish growth) progressions during the spring and early summer (April-June). Mean water temperatures from ice-out to 28 June (11.98-14.62 °C) had significant relationships with mean depth (P < 0.01, R? = 0.85), max depth (P < 0.01, R? = 0.73), and total volume (P < 0.01, R2 = 0.54). Hatch periods ranged from 13 to 19 days in 2015 and 13 to 25 days in 2016. Cumulative degree-days (CDD) were used to predict Yellow Perch hatch periods and explain growth. CDD predicted 21-81% of hatch periods in 2015 and 11-50% in 2016. Mean predicted total lengths at 28 June were 19.65-30.41 mm in 2015 and 20.88-28.54 mm in 2016. There was a significant relationship between CDD and predicted total length (R? = 0.62, P < 0.01) to explain differences in Yellow Perch total length while inhabiting the pelagic zone. Observed gape measurements were highly correlated with predicted gapes from the Schael formula (R? = 0.89, P < 0.01) that was used to assess the availability of edible sized zooplankton for age-0 Yellow Perch in each lake. No predator-prey mismatches were found and earlier hatch dates produced age-0 Yellow Perch with greater predicted total lengths in late June on the majority of lakes. This suggests that earlier hatched Yellow perch have an advantage over later hatched Yellow Perch in attaining greater lengths by late June. Our study provides information on a variety of physical and biological progressions in lakes, which may be used for fisheries management practices in the future.

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins

Selected Works Temporary Series

This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …

Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins

Departmental Papers (Biology)

This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …

Population Characteristics Of A Closed Northern Pike (Esox Lucius) Catch-And-Release Population In Minnesota, John Kempe

Biology Graduate Theses

Literature regarding catch-and-release populations of Northern Pike are rare and provide a unique perspective on their population dynamics. Shingobee Lake is a 64- ha mesotrophic lake with a maximum depth of 12.2 m located in northern Minnesota. Northern Pike fishing has been catch-and-release only since 2005, and there are no public accesses on the lake. Annual ice-out trap-netting occurred from 2009-2017, and a sizable amount of the Northern Pike recaptured via trapnet or angling had been previously tagged (37-59%). The lack of exploitation and high tagging percentage provided a unique opportunity to study the population dynamics of Northern Pike. Shinogbee’s …

Effects Of Food Consumption On Cell Proliferation In The Brain Of Python Regius, Stacy Star Habroun

Master's Theses

Neurogenesis is an important and vastly under-explored area in reptiles. While the ability to generate new brain cells in the adult mammalian brain is limited, reptiles are able to regenerate large populations of neuronal cells. Pythons exhibit a characteristic specific dynamic action (SDA) response after food intake with an increase in metabolic rate that facilitates processing the meal. Associated with this change in SDA, pythons (Python spp.) also exhibit impressive plasticity in their digestive and cardiovascular physiology due to the sheer magnitude of the increase in organ growth that occurs after a meal to speed digestion, absorption, and assimilation of …