Animal Experimentation and Research Commons^™

Downregulation Of Mir-10a-5p As A Potential Therapeutic Target To Improve The Detrimental Effects Of Post-Stroke Social Isolation, Patrick Mooz

Dissertations and Theses (Open Access)

Introduction

Social isolation is detrimental to health. Isolation and loneliness are linked to all-cause mortality and accelerated disease progression in patients with cancer, dementia, and vascular disease. The number of individuals that live alone is increasing in our society, especially in the elderly, and loneliness and isolation represent a profound growing public health challenge. Previous studies have found that the detrimental effects of social isolation can be recapitulated in animal models. Mice that are socially isolated (SI) prior to an experimental stroke have larger infarcts and significantly worse outcomes. Importantly, animals that remain pair housed (PH) when an experimental stroke …

A Signal To Divide: Apoptotic Extracellular Vesicles As Carriers Of Mitogenic And Immunogenic Signals, Safia Essien, Safia Essien

Dissertations and Theses (Open Access)

Efficient replacement of dead cells in epithelial tissue is crucial for maintaining barrier function and tissue homeostasis. Apoptotic cells can signal to neighboring cells to stimulate proliferation and compensate for cell loss and maintain overall cell numbers in normal physiology and cancer. While dying cells can transmit instructive cues to neighboring cells, the molecular mechanisms that induce cell division are not well understood. Recent evidence suggests that apoptotic bodies (ABs) or apoptotic extracellular vesicles (AEVs) mediate cell-to-cell communication and carry diverse biologically active cellular cargo which can influence cell proliferation. This dissertation visualizes and characterizes AEVs in larval zebrafish and …

Unlocking The Mysteries Of Opportunism: Neuroendocrine Insights From An Aseasonal Breeder (Taeniopygia Guttata), Jessica A. Moodie

Graduate Theses and Dissertations (2019 - present)

The regulation of reproductive physiology in animals is mediated by the Hypothalamus-Pituitary-Gonad (HPG) axis. In seasonal breeders, a conserved reciprocal switching of deiodinase enzymes alters thyroid hormone signaling, which controls HPG activity. This study tested the hypothesis that neural regulation of the HPG axis as described in seasonal systems is conserved and repurposed to respond to other cues in aseasonal species. Using water deprivation and nest restriction in the opportunistic Zebra Finch, we were able to create a breeding group and non-breeding group, confirmed by egg laying and changes in ovarian anatomy. Breeding females had clear follicular hierarchy, increased ovary …

Determination Of P Availability In Feedstuffs And The Effect Of Feedstuffs And Anti-Nutritional Factors On Secretory Iga Production And Host Nutrient Losses In Poultry, Benjamin Parsons

Graduate Theses and Dissertations

The availability of P in feedstuffs and the effect of feedstuffs, feed additives, and anti-nutritional factors on secretory IgA (sIgA) production in chickens were evaluated. A rapid method was developed using the precision-fed rooster assay to evaluate phytic acid disappearance, P digestibility, and phytase efficacy. Further, exogenous phytase was found to be effective at degrading myo-inositol 1,2,3,4,5,6-hexakis, however, the enzyme was less efficient at P release from lower inositol phosphates. The availability of P in feedstuffs was found to be affected by dietary Ca content, where increasing Ca linearly reduced (P < 0.05) both phytic acid hydrolysis and P digestibility. For example, the standardized ileal digestibility of P was reduced from 73 to 47% in soybean meal when the dietary Ca content was increased from 0.30 to 0.75%. The digestibility of P in distillers dried grains with solubles (DDGS) and corn fermented protein (CFP), however, was high across all Ca levels (71 to 80%). Relative P bioavailability based on tibia bone ash was also found to be high for DDGS and CFP, being 81 and 78%, respectively. Upon further evaluation, it was observed that utilizing low dietary Ca levels (0.30%) when P digestibility in individual plant-based feedstuffs was determined overestimated the P digestibility in practical grower diets by up to 16 percentage units. Utilization of higher Ca levels (0.75%) when P digestibility in individual plant-based feedstuffs was determined, however, resulted in calcualted P digestibility values that were within 1 to 3 percentage units of the measured digestibility in practical grower diets. Aside from P, feedstuffs were also evaluated to determine their effect on sIgA production in the intestine. Roosters excreted approximately 6 to 30 mg of sIgA / 24 h. Further, the proportional contribution of sIgA to total endogenous amino acid (AA) losses ranged from 1 to 13%, with the greatest contribution being observed for Trp. The addition of casein to a protein-free diet increased (P < 0.05) sIgA production in both roosters and broiler chickens. There was no change (P > 0.05) in sIgA production compared with the protein-free diet …

Assessment Of Dietary Energy And Amino Acid Diet Formulation In The Modern Broilers, Matheus Freitas Costa

Graduate Theses and Dissertations

As a result of the advancement of genetics, understanding broiler requirements for dietary energy and amino acids is essential for improving live performance and carcass characteristics. The energy system used to formulate diets in poultry is based on metabolizable energy (ME); this equation can be described as the total amount of energy in the feed minus gases and feces. However, the net energy (NE) system may be the best depiction of the energy utilized by birds for production and maintenance purposes once the heat increment (HI) is measured. Thus, a series of studies were conducted to establish the responsiveness of …

The Effects Of Probiotics And Environment On The Swine Gut Microbiome, Bin Zuo

Graduate Theses and Dissertations

The gastrointestinal tract is crucial for nutrient absorption and immune system functionality. It employs a synergistic approach, merging physical and biochemical defenses, to counteract pathogens that enter through dietary or other external routes. This system also facilitates the breakdown of complex carbohydrates, a process beyond the host's innate capacity. In swine, gut microbiota early colonization plays a significant role in several physiological developments, shaped by a variety of determinants including maternal factors and environmental conditions. In the swine industry, the shift to indoor pig farming enhances efficiency but limits soil interaction, potentially impacting gut microbiota diversity. Additionally, the practice of …

Brain Microvascular Endothelial Cells Possess A Second Cilium That Arises From The Daughter Centriole, Karthikeyan Thirugnanam, Ankan Gupta, Francisco Nunez, Shubhangi Prabhudesai, Amy Y. Pan, Surya M. Nauli, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Primary cilia from the brain microvascular endothelial cells (ECs) are specialized cell-surface organelles involved in mediating sensory perception, cell signaling, and vascular stability. Immunofluorescence (IF) analysis of human primary brain microvascular ECs reveals two cilia per cell. To confirm the in vitro observation of the two-cilia phenotype in human primary brain ECs, ECs isolated from mouse brain were cultured and stained for cilium. Indeed, brain ECs from a ciliopathic mouse (polycystic kidney disease or Pkd2−/−) also possess more than one cilium. Primary cilium emerges from the mother centriole. Centriole analysis by IF suggests that in brain ECs, markers …

Diabetes-Associated Hyperglycemia Causes Rapid-Onset Ocular Surface Damage, Judy Weng, Christopher Ross, Jacob Baker, Saleh Alfuraih, Kiumars Shamloo, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The metabolic alterations due to chronic hyperglycemia are well-known to cause diabetes-associated complications. Short-term hyperglycemia has also been shown to cause many acute changes, including hemodynamic alterations and osmotic, oxidative, and inflammatory stress. The present study was designed to investigate whether diabetes-associated hyperglycemia can cause rapid-onset detrimental effects on the tear film, goblet cells, and glycocalyx and can lead to activation of an inflammatory cascade or cellular stress response in the cornea.

Methods: Mouse models of type 1 and type 2 diabetes were used. Tear film volume, goblet cell number, and corneal glycocalyx area were measured on …

Untargeted Metabolomics Analysis On Kidney Tissues From Mice Reveals Potential Hypoxia Biomarkers, Muhammad Imran Sajid, Francisco J. Nunez, Farideh Amirrad, Moom Rahman Roosan, Tom Vojtko, Scott Mcculloch, Amal Alachkar, Surya M. Nauli

Pharmacy Faculty Articles and Research

Chronic hypoxia may have a huge impact on the cardiovascular and renal systems. Advancements in microscopy, metabolomics, and bioinformatics provide opportunities to identify new biomarkers. In this study, we aimed at elucidating the metabolic alterations in kidney tissues induced by chronic hypoxia using untargeted metabolomic analyses. Reverse phase ultrahigh performance liquid chromatography-mass spectroscopy/mass spectroscopy (RP–UPLC–MS/MS) and hydrophilic interaction liquid chromatography (HILIC)–UPLC–MS/MS methods with positive and negative ion mode electrospray ionization were used for metabolic profiling. The metabolomic profiling revealed an increase in metabolites related to carnitine synthesis and purine metabolism. Additionally, there was a notable increase in bilirubin. Heme, N-acetyl-L-aspartic …

Sex Differences In Stress Reactivity, Brain Morphology, And Oxytocin In The Hypothalamus Of The Gray Short-Tailed Opossum (Monodelphis Domestica), Esperanza I. Zacarias, Daniela Rodriguez, Alexandra Chalons, Sasawan Heingraj, Nicole Altamirano, Joseph Rafac, John L. Vandeberg, Mario Gil

Research Colloquium

Understanding the effects of stress on behavior and cognition is important due to its impact on mental health and wellbeing (Schneiderman et al. 2005). Translational animal research can contribute to the development of new treatments that can improve therapeutic outcomes and our understanding of the neurobiology of stress. In the present study, we complement behavioral stress reactivity with immunohistochemical localization of oxytocin in the hypothalamus, a neuropeptide that regulates stress (Neumann & Slattery, 2016). Oxytocin has potential therapeutic use for mental health disorders (Neumann & Slattery, 2016), and the effects of oxytocin seem to be sexually dimorphic (Love, 2018). Using …

Murine Models Of Graft Versus Host Disease (Gvhd): Focus On Ocular Gvhd, Philipp Steven, Victor L. Perez, Ajay Sharma

Pharmacy Faculty Articles and Research

Graft versus host disease (GVHD) remains a major and serious complication of allogeneic hematopoietic stem cell transplantation. Based on the time of onset, clinical phenotypes, progression kinetics, and pathophysiology, GVHD is stratified into acute, chronic, and overlapping types. The eyes are among the most commonly affected organs in GVHD. Mouse models have played an important role in understanding the several key elements of GVHD pathobiology. The current review discusses the immunology, pathology, and key phenotypic features of mouse models of systemic GVHD. Furthermore, a critical appraisal of mouse models of ocular GVHD (oGVHD) is provided. The disease mechanisms …

Folate Conjugated Nanomedicines For Selective Inhibition Of Mtor Signaling In Polycystic Kidneys At Clinically Relevant Doses, Rajasekharreddy Pala, Ayan K. Barui, Ashraf M. Mohieldin, Jing Zhou, Surya M. Nauli

Pharmacy Faculty Articles and Research

Although rapamycin is a very effective drug for rodents with polycystic kidney disease (PKD), it is not encouraging in the clinical trials due to the suboptimal dosages compelled by the off-target side effects. We here report the generation, characterization, specificity, functionality, pharmacokinetic, pharmacodynamic and toxicology profiles of novel polycystic kidney-specific-targeting nanoparticles (NPs). We formulated folate-conjugated PLGA-PEG NPs, which can be loaded with multiple drugs, including rapamycin (an mTOR inhibitor) and antioxidant 4-hydroxy-TEMPO (a nephroprotective agent). The NPs increased the efficacy, potency and tolerability of rapamycin resulting in an increased survival rate and improved kidney function by decreasing side effects and …

Digestible And Metabolizable Energy In Ground Yellow Corn, Rice Bran, And Copra Meal Fed To 10 To 15 Kg Philippine Native Pigs (Benguet Strain), Mary Arnel D. Garcia

The Philippine Agricultural Scientist

The experiment was conducted to determine the digestible energy (DE), metabolizable energy (ME), and apparent total tract digestibility (ATTD) of gross energy in ground yellow corn, rice bran, and copra meal when fed to Philippine native pigs. Nine barrows with an average initial bodyweight of 10 kg and ages ranging from 60 to 75 d old were housed individually in metabolism crates and randomly allotted to a triplicated incomplete 3 × 2 Latin square design with three diets and two periods. A corn-based diet containing 94.89% yellow corn and two diets containing 66.42% yellow corn and 30% rice bran or …

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Evaluation Of The Virulence Potential Of Avian Pathogenic Escherichia Coli Isolated From Broiler Breeders With Colibacillosis In Mississippi, Jiddu Joseph

Theses and Dissertations

Avian pathogenic Escherichia coli (APEC) is a bacterium that is responsible for colibacillosis in birds. However, information about broiler breeder APEC isolates is limited, but the data is critical due to the transfer of this bacteria down the production pyramid to progenies resulting in high mortality. Therefore, we evaluated the phenotypic virulence characteristics of 28 isolates using embryo lethality and day-old chick challenge assays. Also, the in vitro adhesion and invasion potential of selected nine isolates were identified. Results showed more than 1/3^rd of the isolates were highly virulent and the virulence increased as the number of virulence-associated genes …

Effects Of Sex And Estrous Cycle On Intravenous Oxycodone Self-Administration And The Reinstatement Of Oxycodone-Seeking Behavior In Rats, Nicole M. Hinds, Ireneusz D. Wojtas, Corinne A. Gallagher, Claire M. Corbett, Daniel F. Manvich

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a …

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …

Evaluation Of Anti-Hyperuricemic Effects Of Alocasia Longiloba Miq. (Keladi Candik) Extracts In Potassium Oxonate Induced Rat Model, Ferid Abdulhafiz, Arifullah Mohammed, Mohd Farhan Hanif Reduan, Zulhazman Hamzah, Zulhisyam Abdul Kari, Guillermo Tellez-Isaias

Poultry Science Faculty Publications and Presentations

Hyperuricemia has become a significant public-health concern in recent years, and the available treatments have been reported to have an adverse side effect on patients. Alocasia longiloba has been used traditionally in Malaysia for treating gout, inflammation, and wounds. However, the plant has not been investigated for its effects on hyperuricemia. This study investigated the anti-hyperuricemic and anti-inflammatory effects of A. longiloba extracts in hyperuricemic rats induced by potassium oxonate (250 mg/kg body weight). Rats were given A. longiloba extracts or a standard drug for two-week, and blood and tissue samples were collected for analysis. Results show that A. longiloba …

Alcohol As A Modifiable Risk Factor For Alzheimer’S Disease—Evidence From Experimental Studies, Devaraj V. Chandrashekar, Ross A. Steinberg, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive impairment and memory loss. Epidemiological evidence suggests that heavy alcohol consumption aggravates AD pathology, whereas low alcohol intake may be protective. However, these observations have been inconsistent, and because of methodological discrepancies, the findings remain controversial. Alcohol-feeding studies in AD mice support the notion that high alcohol intake promotes AD, while also hinting that low alcohol doses may be protective against AD. Chronic alcohol feeding to AD mice that delivers alcohol doses sufficient to cause liver injury largely promotes and accelerates AD pathology. The mechanisms by which alcohol can …

Investigating Sexual Dimorphism In Lateral Hypothalamic Melanin-Concentrating Hormone Neuron Subpopulations, Mahitha Juttu

Honors Scholar Theses

The lateral hypothalamic area (LHA) is an area crucial for coordinating key behaviors such as sleep, wakefulness, stress, and feeding. Within this area in the brain, Melanin concentrating hormone (MCH) neurons are exclusive to the LHA and also contribute to these key homeostatic behaviors. These neurons can be divided into two different subpopulations: MCH neurons that express cocaine amphetamine-regulated transcript (CART) tachykinin-3 receptor (NK3R) and MCH neurons that do not express CART and NK3R. These neuronal subpopulations have been implicated in coordinating key behaviors but have not been well studied.

In this paper, our project seeks to analyze how the …