Animal Experimentation and Research Commons^™

Stress Granule Formation Helps To Mitigate Neurodegeneration, M. Rebecca Glineburg, Evrim Yildirim, Nicolas Gomez, Genesis Rodriguez, Jaclyn Pak, Xingli Li, Christopher Altheim, Jacob Waksmacki, Gerald M. Mcinerney, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cellular stress pathways that inhibit translation initiation lead to transient formation of cytoplasmic RNA/protein complexes known as stress granules. Many of the proteins found within stress granules and the dynamics of stress granule formation and dissolution are implicated in neurodegenerative disease. Whether stress granule formation is protective or harmful in neurodegenerative conditions is not known. To address this, we took advantage of the alphavirus protein nsP3, which selectively binds dimers of the central stress granule nucleator protein G3BP and markedly reduces stress granule formation without directly impacting the protein translational inhibitory pathways that trigger stress granule formation. In Drosophila and …

Assessment Of American Tannin-Free Grain Sorghum As Feedstuff For Poultry: Nutrient Composition, Amino Acid Digestibility And Bird Performance, Santiago Sasia

All Dissertations

Given the rising cost of poultry diets, alternative ingredients like sorghum are crucial for maximizing returns without compromising product quality. Sorghum's drought tolerance and adaptability, along with its nutritional profile, make it a viable corn substitute. This dissertation examines the nutrient composition, amino acid digestibility, and performance of poultry fed with American tannin-free grain sorghum. Chapter II evaluates the impact of sorghum-based diets, with or without phytase superdosing, on broiler performance, including body weight, weight gain, feed intake, and feed conversion ratio. Results indicate that sorghum can replace corn without adverse effects on broiler performance. Chapter III explores the partial …

Microplastic Accumulation In The Marsh Periwinkle (Littoraria Irrorata), Sarah Keaton, Hannah Lukhard, Eli Windy, Manar Hasan

DePaul Discoveries

Contamination of oceans by microplastics (mm) currently poses a major threat to aquatic and terrestrial ecosystems worldwide. Recent attention towards this issue has raised questions about the extent to which microplastics have accumulated in the environment, and has led to an increase in studies on the effects of microplastics in various organisms. However, levels of contamination in protected natural areas are still largely unexplored, yet can offer an important empirical perspective on the issue. In addition, little is known about the potential effects of microplastics on behavior in the field. This research was conducted within the protected ACE Basin National …

Antidepressant Effect Of Enzymatic Porcine Placenta Hydrolysate In Repeated Immobilization Stress-Induced Ovariectomized Female Mice, Minsook Ye, Sharon Nguyen, Min Ju Kim, Jee Sun Hwang, Gun Won Bae, Keun-Hang Susan Yang, Insop Shim

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

When postmenopausal women are under stress conditions, this exacerbates mood disorders and issues with neuroimmune systems. The porcine placenta is known to relieve menopausal depression in clinical trials, but its underlying mechanisms for depression and anti-inflammatory functions remain poorly defined. The present study was designed to examine the anti-inflammatory effects of enzymatic porcine placenta hydrolysate (EPPH) on LPS-induced levels of nitric oxide (NO), prostaglandin E2 (PGE2), corticosterone (CORT), and pro-inflammatory cytokine interleukin-1 beta (IL-1β) in RAW 264.7 macrophage cells. In addition, the neurite outgrowth of PC12 cells was evaluated to examine the effects of EPPH on neurite growth. To mimic …

Hepatic Lrp-1 Plays An Important Role In Amyloidosis In Alzheimer's Disease Mice: Potential Role In Chronic Heavy Alcohol Feeding, Devaraj V. Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Urvashi R. Panchal, Adenike Oyegbesan, Oghenetega E. Imiruaye, Hai Zhang, Jerome Garcia, Kamaljit Kaur, Sanda Win, Tin A. Than, Neil Kaplowitz, Moom R. Roosan, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Methods

Positron Emission Tomography In Oncology And Environmental Science, Samantha Delaney

Dissertations, Theses, and Capstone Projects

The last half century has played witness to the onset of molecular imaging for the clinical assessment of physiological targets. While several medical imaging modalities allow for the visualization of the functional and anatomical properties of humans and living systems, few offer accurate quantitation and the ability to detect biochemical processes with low-administered drug mass doses. This limits how physicians and scientists may diagnose and treat medical issues, such as cancer, disease, and foreign agents.

A promising alternative to extant invasive procedures and suboptimal imaging modalities to assess the nature of a biological environment is the use of positron emission …

Cis-Regulatory Mechanisms Through Stages Of Erythroid Regenration, Yichao Zhou

Theses & Dissertations

Produced by steady state erythropoiesis, erythrocytes serve as vital regulators of metabolism and life by delivering oxygen to all the cells and tissues. Under acute anemia, steady state erythropoiesis is not sufficient to produce enough erythrocytes, leading to distinct mechanisms needed to regenerate large numbers of mature erythrocytes rapidly. Erythroid regeneration occurs in four stages: activation, expansion and differentiation, resolution, and post-resolution, according to the dynamics of erythrocyte numbers and progenitor activity. Erythroid regeneration throughout this timeline requires some critical extracellular cues, but the intrinsic molecular mechanisms needed to accelerate and decelerate the activity of erythroid progenitors in anemia and …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Effect Of Source Of Trace Minerals On Nutrient Digestibility And Rumen Fermentation Of Dairy Cows, Cesar Velasquez Rios

All Theses

none

Effects Of Kappa Opioid Receptor Manipulation On Methamphetamine-Induced Behavioral Sensitization In Adolescent Male And Female Rats, Hiroyoshi Matsui Mr, Sarah Seeley, Manoranjan S. D'Souza

ONU Student Research Colloquium

Methamphetamine abuse amongst adolescents has been on the rise in the United States. In this study, we assessed the effects of manipulation of KORs on methamphetamine-induced behavioral sensitization in adolescent male and female rats. Methamphetamine-induced behavioral sensitization is an animal model to study methamphetamine addiction. Behavioral sensitization usually occurs in animals who have been treated with methamphetamine followed by a period of withdrawal. It is hypothesized that brain circuits are altered during the period of withdrawal after methamphetamine exposure resulting in sensitized (increased) responses to methamphetamine at the end of the withdrawal period. The experiment was conducted over 28 days. …

Apigenin Alleviates Autistic-Like Stereotyped Repetitive Behaviors And Mitigates Brain Oxidative Stress In Mice, Petrilla Jayaprakash, Dmytro Isaev, Keun-Hang Susan Yang, Rami Beiram, Murat Oz, Bassem Sadek

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Studying the involvement of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in neuropsychiatric brain disorders such as autism spectrum disorder (ASD) has gained a growing interest. The flavonoid apigenin (APG) has been confirmed in its pharmacological action as a positive allosteric modulator of α7-nAChRs. However, there is no research describing the pharmacological potential of APG in ASD. The aim of this study was to evaluate the effects of the subchronic systemic treatment of APG (10–30 mg/kg) on ASD-like repetitive and compulsive-like behaviors and oxidative stress status in the hippocampus and cerebellum in BTBR mice, utilizing the reference drug aripiprazole (ARP, 1 …

Materials And Methods Developed For The Recording And Analysis Of Behavior In The Common Marmoset (Callithrix Jacchus)., Christian Wintle

UNO Student Research and Creative Activity Fair

Materials and methods developed for the recording and analysis of behavior in the common marmoset (Callithrix jacchus).

Christian J. Wintle^a, Jordan B. Hernandez^a,b,c, Dobromir Dotov^d, and Jonathan B. Clayton^a,b,e,f,g

^aDepartment of Biology, University of Nebraska at Omaha, Omaha, NE, USA

^bNebraska Food for Health Center, University of Nebraska-Lincoln, Lincoln, NE, USA

^cDepartment of Genetics, Cell Biology, and Anatomy, University of Nebraska Medical Center, NE, USA

^dDepartment of Biomechanics, University of Nebraska at Omaha, Omaha, NE, USA

^eDepartment of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, …

Modulation Of Hippocampal Protein Expression By A Brain Penetrant Biologic Tnf-Α Inhibitor In The 3xtg Alzheimer’S Disease Mice, Nataraj Jagadeesan, G. Chuli Roules, Devaraj V. Chandrashekar, Joshua Yang, Sanjana Kolluru, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Biologic TNF-α inhibitors (bTNFIs) can block cerebral TNF-α in Alzheimer’s disease (AD) if these macromolecules can cross the blood–brain barrier (BBB). Thus, a model bTNFI, the extracellular domain of type II TNF-α receptor (TNFR), which can bind to and sequester TNF-α, was fused with a mouse transferrin receptor antibody (TfRMAb) to enable brain delivery via BBB TfR-mediated transcytosis. Previously, we found TfRMAb-TNFR to be protective in a mouse model of amyloidosis (APP/PS1) and tauopathy (PS19), and herein we investigated its effects in mice that combine both amyloidosis and tauopathy (3xTg-AD).

Methods

Eight-month-old female 3xTg-AD mice were injected intraperitoneally with …

Limonene Exerts Anti-Inflammatory Effect On Lps-Induced Jejunal Injury In Mice By Inhibiting Nf-Κb/Ap-1 Pathway, Sarmed H. Kathem, Yasameen Sh. Nasrawi, Shihab H. Mutlag, Surya M. Nauli

Pharmacy Faculty Articles and Research

The human gastrointestinal system is a complex ecosystem crucial for well-being. During sepsis-induced gut injury, the integrity of the intestinal barrier can be compromised. Lipopolysaccharide (LPS), an endotoxin from Gram-negative bacteria, disrupts the intestinal barrier, contributing to inflammation and various dysfunctions. The current study explores the protective effects of limonene, a natural compound with diverse biological properties, against LPS-induced jejunal injury in mice. Oral administration of limonene at dosages of 100 and 200 mg/kg was used in the LPS mouse model. The Murine Sepsis Score (MSS) was utilized to evaluate the severity of sepsis, while serum levels of urea and …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Zebrafish Drug Screening Identifies Erlotinib As An Inhibitor Of Wnt/ Β-Catenin Signaling And Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd A. Al-Hamaly, Anna H. Cox, Meghan G. Haney, Wen Zhang, Emma C. Arvin, Shilpa Sampathi, Mary Wimsett, Chunming Liu, Jessica S. Blackburn

Markey Cancer Center Faculty Publications

The Wnt/β-catenin pathway’s significance in cancer initiation, progression, and stem cell biology underscores its therapeutic potential. However, the clinical application of Wnt inhibitors remains limited due to challenges posed by off-target effects and complex cross-talk of Wnt signaling with other pathways. In this study, we leveraged a zebrafish model to perform a robust and rapid drug screening of 773 FDA-approved compounds to identify Wnt/β-catenin inhibitors with minimal toxicity. Utilizing zebrafish expressing a Wnt reporter, we identified several drugs that suppressed Wnt signaling without compromising zebrafish development. The effi- cacy of the top hit, Erlotinib, extended to human cells, where it …

The Delineation Of Platelet Pathology In Cardiometabolic Disease, Chi Peng

Theses and Dissertations--Pharmacology and Nutritional Sciences

Obesity is a multifactorial disease with many comorbidities leading to multiorgan dysfunction. Current studies point towards dysregulation of platelet signaling as a driver for increased risk of cardiovascular disease and stroke. The exact mechanisms remain elusive due to the complex interplay of factors involved, warranting the need to further understand how platelets are affected. Our preliminary data evaluating changes in platelet and coagulation parameters from bariatric patients showed that obesity did not affect platelet count or clotting time as demonstrated in INR values. However, female patients had increased bleeding events before surgery that were decreased after surgery. Due to limitations …

Novel Engineering Approaches For Orthopedic Injury Treatment And Infection Diagnosis, Cynthia Co

Bioengineering Dissertations - Archive

Bioengineering has made significant contributions to the treatment of orthopedic injury through interdisciplinary approaches. Central to these advancements are many orthopedic implants, including anchors and joint replacements, which have been designed to restore mobility. Despite their functional efficacy, these products have limited lifespan and are associated with many complications, such as implant-associated infection. The success of implant design and function, both in the short and long term, is paramount for enhancing patient outcomes and overall well-being. Therefore, my thesis work is dedicated to addressing these critical challenges, aiming to maximize their treatment effect while minimizing the implant-associated complications.

Long-term patient …

Observed Effects Of Physiological Melatonin Dosing On Mda-Mb-231 Breast Cancer Cell Proliferation, Wenli Wu

Williams Honors College, Honors Research Projects

This project seeks to evaluate pharmacological dosing of melatonin on the cell proliferation of MDA-MB-231 breast cancer cell line in culture, using the two solubility carriers: DMSO/water and ethanol. This experiment is a component of ongoing research at the Eaton lab which will elucidate melatonin dose-response toxicology in zebrafish and a possible breast cancer xenograft model for novel treatment therapies.

Impact Of Oxytocin And Tetrahydrocannabinol On Signs Of Fear In The Rat, Jair E. Alvarez Jr.

EWU Masters Thesis Collection

BACKGROUND: Oxytocin (OXT) has been used as a post-treatment for post-traumatic stress disorder (PTSD). Previous research suggests that pre-treatment of intranasal OXT attenuates signs of fear in rats; however, the impact of intraperitoneal (i.p) OXT pre-treatment on signs of fear in rats is unknown. We also explored the effects of delta-9 (psychoactive component of cannabidiol) and delta-8 (delta-9 isomer) THC pre-treatment on attenuating signs of fear in the rat. METHODS: For each experiment, male Sprague-Dawley rats were divided into 5 groups, (n=8 per group); 1.) controls (vehicle and no foot shock), 2.) shock (vehicle and foot shock), 3.) low dose …

Mild Traumatic Brain Injury In Yucatan Minipigs: Assessing Changes In Approachability And Mechanical Nociception Following Diffuse Central Fluid Percussion Injury, Mark D. Pavlichenko

Theses and Dissertations

Traumatic brain injury (TBI) is a major healthcare concern affecting millions. Symptoms of TBI include sensory sensitivity and social changes that may persist long-term. Due to similarities in cytoarchitecture, metabolism, and inflammation, higher order minipig models are advantageous for translational TBI research, however, there remains a shortage of information regarding their behavioral and sensory sequelae following injury. Therefore, in this study, we assessed changes in sociability and somatosensation in adult male and female Yucatan minipigs for up to one-week following a sham or central fluid percussion injury (cFPI). Specifically, the voluntary human approach task (VHAT) and the forced human approach …

Metalloproteomic Investigation Of Hg-Binding Proteins In Renal Tissue Of Rats Exposed To Mercury Chloride, Emerson Carlos De Almeida, Victor Diego Faria, Felipe Dalmazzo Cirinêu, Maria G.A. Santiago, Beatriz Miotto, José C.S. Vieira, Camila Pereira Braga, Jiri Adamec, Ana A.H. Fernandes, Marília A.R. Buzalaf, Pedro De Magalhães Padilha

School of Medicine Faculty Publications

Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins …

The Effects Of Sex Hormones On The Size Of Intestinal Lipoproteins, Andromeda M. Nauli, Ann Phan, Patrick Tso, Surya M. Nauli

Pharmacy Faculty Articles and Research

Larger intestinal lipoproteins are more likely to be retained longer in the intestinal wall, allowing more time for their fat to be hydrolyzed and subsequently taken up by the abdominal viscera. Since men generally accumulate more abdominal visceral fat than women, we sought to determine if males produce larger intestinal lipoproteins compared to females. Using the conscious lymph fistula mouse model, we discovered that the male mice indeed produced larger intestinal lipoproteins than the female mice when they were intraduodenally infused with lipid emulsion. We then employed our differentiated Caco-2 cell model with semipermeable membrane system to determine the effects …

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

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 …

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 …