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Uncovering A Fundamental Mechanism Underlying Female Oocyte Quality And Rasopathies Using C. Elegans As A Model System, Han Bit Baek

Dissertations and Theses (Open Access)

Signaling pathways are molecular networks that allow cells to communicate between and within themselves. They are crucial for the coordination of diverse cellular processes and are the molecular mechanism in which cells sense and respond to their environment. RAS (Rat Sarcoma) is a small GTPase that transmits extracellular growth factor signals through a downstream kinase cascade and ERK (Extracellular-signal regulated kinase) is the terminal kinase, and it controls cellular processes such as proliferation, differentiation, and survival by phosphorylating its downstream effectors. This post translational modification regulates the effector by modulating its activity, levels, and/or interaction with other molecules. Given the …

Exploring The Immunologic Consequences Of Atrx Deficiency In Glioma, Benjamin Whitfield

Dissertations and Theses (Open Access)

ATRX is a key chromatin regulator that is frequently mutated across multiple cancer types. One of the most common ATRX-mutated tumor types is the adult-type glioma, IDH-mutant, Astrocytoma. It is known that ATRX mutation leads to increases in DNA damage, replication stress, and global epigenetic regulation at a cell level; however, less is known about the impact of ATRX mutation on immune signaling. Furthermore, little is known about the interaction of ATRX loss with gain-of-function mutations in IDH. In this paper we set out to explore the impact of ATRX loss on immune signaling in gliomas, both in the context …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Evaluating Bone Fracture Healing In A Rabbit Model Using Doppler Imaging Modes, Shear Wave Elastography, X-Ray, And Dual-Energy X-Ray Absorptiometry, Priscilla Machado, Rachel Blackman, Ji-Bin Liu, Collleen Dempsey, Flemming Forsberg, Traci Fox

Department of Radiology Faculty Papers

OBJECTIVE: This study investigated methods of evaluating the bone fracture healing process using superb microvascular imaging (SMI; two modes color SMI [cSMI] and monochromeSMI [mSMI]), and shear wave elastography (SWE), relative to X-ray, dual-energy X-ray absorptiometry (DXA), and platelet endothelial cell adhesion molecule 1 (PECAM-1) also know as cluster of differentiation 31 (CD-31) staining in a rabbit model.

METHODS: This IACUC-approved study involved eight rabbits that underwent a bilateral fibula osteotomy and were followed for 7 or 21 days (Groups 1 and 2 with 4 rabbits in each). Ultrasound examinations using cSMI, mSMI, and SWE were performed on Days 0, …

Rooted In Play: Empowering Development Through Nature-Based Occupational Therapy, Nicole Roper

Occupational Therapy Doctoral Capstones

The doctoral capstone project included advocating for the use of outdoor play by identifying and emphasizing the benefits of occupational therapy (OT) involvement within nature-based therapy for pediatric patients and creating nature-based therapy recourses for caregivers and occupational therapists.

Utilizing Animal-Assisted Therapy To Address Pyschosocial Implications Of The Geriatric Population In A Residential Facility, Blaire Kennon Bassham

Occupational Therapy Doctoral Capstones

Older adults in residential care frequently experience psychosocial challenges such as isolation, depression, and reduced engagement in meaningful activity. Animal-Assisted Therapy (AAT), when integrated into occupational therapy, offers a powerful, evidence-based means to address these concerns by promoting emotional well-being, social connection, and purposeful interaction. This capstone project leveraged AAT as a therapeutic intervention specifically designed to meet psychosocial needs.

Insights Into The Role Of The Glymphatic System In The Pathogenesis Of Post-Hemorrhagic Hydrocephalus, Ahmed T Massoud, Dillon A Noltensmeyer, Jenifer Juranek, Charles S Cox, Fred Christian Velasquez, Banghe Zhu, Eva M Sevick-Muraca, Manish N Shah

The Brown Foundation: Institute of Molecular Medicine

Recently, it has been well-established that the glymphatic or glial-lymphatic system plays a vital role in the pathophysiology of various neurological compromise, especially hydrocephalus (HCP). Till now, the complete pathway is not yet fully understood, and little evidence is available from the literature that links hydrocephalus to disorders of the glymphatic system. Most published molecular studies and animal research have shown that, in models with hydrocephalus, the drainage of cerebrospinal fluid (CSF) via the glymphatic system is disrupted. This is strongly observed in normal pressure and post-hemorrhagic hydrocephalus cases. A thorough search of the literature to date yields scarce evidence …

A Sex Comparison On The Effects Of Caveolin Scaffolding Domain On Fibrosis Formation After Chronic Sympathetic Stimulation, Crimsyn Price

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. There are various trends that influence the rates of cardiovascular disease in each country. Factors that create these trends involve diet, exercise, genetics, socioeconomic status, and geographical location. Additionally, CVD is typically higher in middle-income and lower-income classes. Hospital routes, rates of poverty, insurance policies, and lifestyle culture are all factors that can impact the time of treatment which in turn affect the rate of CVD. However, we explored in this study the shift in CVD women experience after menopause. Women were excluded from clinical trials until 1986, and the …

Testing A Benign Multi-Modal Bilingual Intervention To Increase Self-Efficacy, Intentions, And Willingness To Administer A Covid-19 Antigen Rapid Test In A Predominately Hispanic Sample, Uchenna Gbugu

Open Access Theses & Dissertations

Introduction. Testing is one of the most effective methods for reducing the spread of COVID-19. COVID-19 antigen tests can detect proteins from the COVID-19 virus called antigens and produce results within minutes, making them suitable for at-home use. Several factors have been identified as barriers to self-administering a COVID-19 antigen test, including the language of the testing instructions, the cost of testing, and access to tests. Interventions to reduce barriers to self-administering COVID-19 rapid tests are warranted to reduce the spread of COVID-19. The purpose of the present study is to test the impact of a benign multi-modal bilingual intervention …

Stereotypic Behaviors And Physiological Indicators Of Stress Occur In Horses With Restricted Durations Of Turnout, Elizabeth E. Rodgers

Department of Animal Science: Dissertations, Theses, and Student Research

The confinement of horses to stalls with limited or no turnout time restricts their natural roaming behaviors, which potentially increases stress and behavioral stereotypies. This study investigated the impact of turnout duration on behavioral and physiological stress indicators in healthy horses. Adult horses (n = 11) were enrolled in a 3 treatment (0-, 15-, and 60-minute turnout/day) Latin square design, including 3 12 d experimental periods over 6 weeks. Horses were acclimated to turnout (24.38 x 64.01m indoor arena) and stalls (2.74 x 4.87m - 3.66 x 3.66m) stalls prior to data collection on day 1. Experienced handlers managed …

Digestibility, Palatability, And Nutrient Composition Of Three Species Of Whole Prey In Three Species Of Snakes, Morgan R. Kienzle

Department of Animal Science: Dissertations, Theses, and Student Research

Snakes in human care often lack diversity in the diet. Rodents account for the majority of meals, while wild snakes are consuming a varied diet composed of multiple different whole prey species. By feeding only one species of prey, the chance of nutrient deficiencies and other health concerns increases. To promote variety in the managed diet, two commercially available whole prey species (mice (Mus musculus) and chicks (Gallus spp.)) and one novel species (Seba’s short-tailed bats (Carollia perspicillata)), were analyzed for their dry matter (DM), organic matter (OM), crude protein (CP), crude fat …

Methane Mitigation And Its Effects On Energy Utilization In Lactating Dairy Cattle, Shan C. Sherwood

Department of Animal Science: Dissertations, Theses, and Student Research

Improved methane (CH₄) mitigation strategies are needed to achieve the greenhouse gas emission goals of the dairy industry. The first experiment was conducted to evaluate the effects of feeding black cumin (Nigella sativa) seed oil and acetate (BCA) on CH₄ production and whole-animal energy utilization. Twelve dry Jersey cows were used in a 2-period crossover design study with 28d periods. The BCA treatment was compared to a control diet with corn oil. Both BCA and corn oil were added to the base diet as a top dress. Results from this study did not show any …

Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease, Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

Over the last 20 years, research into the Meibomian glands of the eyelids has increased exponentially and is now widely recognized as a field of research. It is all the more astonishing that knowledge about another type of gland in the eyelids, the Moll glands or ciliary glands, has almost stagnated and there has been little to almost no progress, even though this type of gland as a whole takes up a relatively large volume in the upper and lower eyelids. There is not much information about the namesake Moll or the function of the glands although these are listed …

Diroximel Fumarate Acts Through Nrf2 To Attenuate Methylglyoxal-Induced Nociception In Mice And Decrease Isr Activation In Drg Neurons, Muhammad Saad Yousuf, Marisol Mancilla Moreno, Brodie J Woodall, Vikram Thakur, Jiahe Li, Lucy He, Rohita Arjarapu, Danielle Royer, Jennifer Zhang, Munmun Chattopadhyay, Peter M Grace, Theodore J Price

Faculty, Staff and Student Publications

Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes pain hypersensitivity in mice by stimulating the phosphorylation of eukaryotic initiation factor 2α (p-eIF2α) and subsequently activating the integrated stress response (ISR). We first established that Zucker diabetic fatty rats have enhanced MGO signaling, engage ISR, and develop pain hypersensitivity. Since nuclear factor erythroid 2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins that neutralize MGO, we hypothesized that fumarates, like diroximel fumarate (DRF), will stimulate Nrf2 signaling, and prevent MGO-induced ISR and pain hypersensitivity. DRF (100 mg/kg) treated …

Unveiling The Intercompartmental Signaling Axis: Mitochondrial To Er Stress Response (Mersr) And Its Impact On Proteostasis, Jeson J Li, Nan Xin, Chunxia Yang, Bo G Kim, Larissa A Tavizon, Ruth Hong, Jina Park, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim

Faculty, Staff and Student Publications

Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and …

From Epithelium To Therapy: Transitional Cells In Lung Fibrosis, Sarah Y Shin, Jichao Chen, Irit Milman Krentsis, Yair Reisner, Rodeo Abrencillo, Rahat Hussain, Danielle Wu, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

Patients with idiopathic pulmonary fibrosis and lung fibrosis secondary to infections such as influenza A and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have limited treatment options outside of supportive therapy and lung transplantation. Multiple lung stem cell populations have been implicated in the pathogenesis of lung fibrosis, and more progenitor cell populations continue to be discovered and characterized. In this review, we summarize the functions and differentiation pathways of various cells that constitute the lung epithelium. We then focus on two subpopulations of KRT5

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Differences In Blood Leukocyte Subpopulations In Schizophrenia: A Systematic Review And Meta-Analysis, Leon Dudeck, Madeleine Nussbaumer, Thomas Nickl-Jockschat, Paul C Guest, Henrik Dobrowolny, Gabriela Meyer-Lotz, Zhongming Zhao, Roland Jacobs, Kolja Schiltz, Brisa S Fernandes, Johann Steiner

Faculty, Staff and Student Publications

Importance: This study aims to provide robust evidence to support or challenge the immune hypothesis of schizophrenia.

Objective: To conduct a meta-analysis of reports on blood leukocyte subpopulations in schizophrenia vs healthy controls, examining disease- and treatment-related differences as well as potential confounders.

Data sources: Systematic database search for English and non-English peer-reviewed articles in PubMed, Web of Science, Scopus, and Cochrane Library databases, with the last search in January 2024.

Study selection: Cross-sectional, case-control, and longitudinal studies comparing leukocyte numbers in patients with schizophrenia and healthy controls. After duplicates were removed, 3691 studies were identified for screening.

Data extraction …

Gonadotropin-Releasing Hormone Ii And Its Receptor: Novel Regulators Of Semen Quality And Follicular Function In Swine, Caitlin Elizabeth Ross

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Pigs are the only mammalian livestock species encoding functional proteins for the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II). In the first study, GnRHR-II localized to developing germ cells and the connecting piece of ejaculated spermatozoa. Concurrently, GnRH-II was most abundantly produced in the testis compared with other reproductive tract organs and was present within seminal plasma. Moreover, treatment of extended semen with GnRHR-II analogues altered sperm motility, morphology, and kinematics. For remaining studies, we utilized a swine line with ubiquitous knockdown of GnRHR-II (GnRHR-II KD) developed in our laboratory. The second study demonstrated that circulating GnRH-II …

Longevity Humans Have Youthful Erythrocyte Function And Metabolic Signatures, Fang Yu, Changhan Chen, Wuping Liu, Zhixiang Zhao, Yuhua Fan, Zhenjiang Li, Weilun Huang, Tingting Xie, Cheng Luo, Zhouzhou Yao, Qi Guo, Zhiyu Yang, Juan Liu, Yujin Zhang, Rodney E Kellems, Jian Xia, Ji Li, Yang Xia

Faculty, Staff and Student Publications

Longevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, …

Pathobiology Of Aortic Aneurysms And Dissections: Synthesis Of Recent Investigations And Evolving Insights, L Maximilian Buja, Bihong Zhao, Deborah Vela, Ana Segura, Navneet Narula

Faculty, Staff and Student Publications

The pathobiology of aortic disease is linked to aortic region: atherosclerosis for abdominal aorta, primary medial degeneration or aortitis for ascending thoracic aorta, and all causes for descending thoracic aorta and thoracoabdominal lesions. The pathogenesis of aortic dissection involves damage of the outer media from impaired perfusion from dysfunctional vasa vasorum, formation of discrete foci of disrupted vascular smooth muscle cell-elastic fiber extension-contractile units, and imbalance of radial sheer stress across the aortic wall, thereby creating an intimal tear and linear dissection. Thoracic aortic aneurysms develop from the chronic progression of medial degeneration coupled with the weakening of the remodeled …

Examination Of The Relationships Between Religious Or Atheistic Belief Certainty And Mental Health Outcomes, Christopher S. Percifield

All-Inclusive List of Electronic Theses and Dissertations

Perceived meaning in life is considered to be an outcome of one’s efforts to create and sustain a sense of subjective understanding and purpose in the world. Meaning-making researchers have historically emphasized the role of religious worldviews as fundamental structures through which meaning-making attempts can be guided. Often, researchers have suggested that religious beliefs offer unique benefits for physical and psychological well-being for religious believers compared to non-believers. Archival data was analyzed across two separate waves, and significant correlates of aspects of meaning in life, belief certainty, and psychological well-being were identified. Perceived meaning and peace and mitigation of lapses …

Manganese-Induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation In Female Rats, Alina M. Hamilton, Vinod K. Srivastava, Jill K. Hiney, William L. Dees, Robert K. Dearth

School of Integrative Biological & Chemical Sciences Faculty Publications

Precocious puberty (PP) is an established breast cancer risk factor. In the normal mammary gland, hormone receptor-positive (HR+) cells rarely proliferate. In breast cancer, proliferating epithelial cells are often HR+. It is not known if PP can modify this population of proliferating HR+ cells. Previously, we established a manganese-induced precocious puberty (MnPP) model to study the effects of PP on mammary gland development in female rats. Here, we characterized the distribution of HR+ proliferating mammary epithelial cells in prepubertal and adult rodents, in association with precocious puberty. Female rats were exposed daily to 10 mg/kg manganese chloride or saline (control) …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

From Trauma To Treatment: Chronic Neurobehavioral Consequences And Emerging Treatments, Moriah E. Mcguier

Dartmouth College Ph.D Dissertations

Severe trauma exposure related to traumatic brain injury (TBI) or psychiatric disorders like post-traumatic stress disorder (PTSD) leads to neurobehavioral and physiological impairments that reduce the quality of life of individuals and remain difficult to treat with current therapeutic options. Further, these conditions are highly comorbid, notably in PTSD with blast-traumatic brain injury (bTBI) commonly experienced by military members via explosive forces, leading to complex and heterogenous outcomes. To address this, preclinical models have been developed to recapitulate aspects of TBI and PTSD. This thesis utilizes two such models in rats, bTBI and the single prolonged stress (SPS) model for …

Small But Mighty: Strengthening The Value Of Local Pocket Parks, Makana Sm Higa

Capstone Projects and Master's Theses

In Monterey County, youth obesity rates are climbing at an alarming rate. Ventana Wildlife Society, and Wellness Through Nature program seek to help lower these rates. Ventana looks to achieve this through outdoor education and family trips with migrant farm working families in the cities of Soledad and Salinas. These trips attempt to increase environmental stewardship and improve community health. The project aims to evaluate the effectiveness and community engagement in regards to pocket parks. The parks visited were Bataan Memorial Park, Harden Neighborhood Park, Cesar Chavez Park, Joe Ledesma Park and San Antonio Park. The research seeks to increase …

Serendipitous Supernormality, Behzad B. Pavri, Eitan Frankel

Division of Cardiology Faculty Papers

We describe a patient who underwent AV node modification to create complete heart block in the setting of incessant, ablation-and-drug-refractory, symptomatic atypical atrial flutter. His dual chamber defibrillator (previously implanted for resuscitated cardiac arrest) was programmed to the VVIR mode at a faster pacing rate of 85 bpm. Serendipitously, this rate was an almost exact factorial of his flutter rate of 250-260 bpm. This resulted in every 6th flutter wave falling in the supernormal period, resulting in fixed-coupled supraventricular bigeminy and trigeminy in the setting of complete heart block. Reprogramming the pacing rate to 75 bpm abolished bigeminy and trigeminy.

Targeting Bard1 Suppresses A Myc-Dependent Transcriptional Program And Tumor Growth In Pancreatic Ductal Adenocarcinoma, Sohum Patel, Eleanor Jenkins, Rutuj P. Kusurkar, Sherry Lee, Wei Jiang, Avinoam Nevler, Matthew Mccoy, Michael J. Pishvaian, Rosalie C. Sears, Jonathan R. Brody, Charles J. Yeo, Aditi Jain

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers demanding better and more effective therapies. BARD1 or BRCA1-Associated -Ring Domain-1 plays a pivotal role in homologous recombination repair (HRR). However, its function and the underlying molecular mechanisms in PDAC are still not fully elucidated. Here, we demonstrate that BARD1 is overexpressed in PDAC and its genetic inhibition suppresses c-Myc and disrupts c-Myc dependent transcriptional program. Mechanistically, BARD1 stabilizes c-Myc through ubiquitin-proteasome system by regulating FBXW7. Importantly, targeting BARD1 using either siRNAs or CRISPR/Cas9 deletion blocks PDAC growth in vitro and in vivo, without any signs of toxicity to mice. …

Novel Application Of Orthopedic Suture Tape For Sternal Closure After Upper Hemisternotomy, Vishal N. Shah, Joshua R. Chen, Konstadinos A. Plestis

Department of Surgery Faculty Papers

The FiberTape (FT) System (Arthrex, Naples, FL, USA), initially developed for orthopedic surgery, is a new, nonmetallic, suture-based alternative to standard stainless-steel wires for sternal reapproximation. Publications on FT use after cardiothoracic surgery are limited. The FT System has not been used in upper hemisternotomy (UHS) closure. Consequently, we report the use of the FT System for sternal closure in a 70-year-old man after UHS aortic valve replacement and discuss several advantages of its application.

Graded Response Of The Pulmonary Circulation To Progressive Pulmonary Embolism In Sheep: From Compensation To Lethal Right Heart Failure, Cheng Zhou, Yuman Li, Kyle Polley, Cherry Ballard-Croft, Masashi Kawabori, Keshava Rajagopal, Joseph B. Zwischenberger, Dongfang Wang

Department of Surgery Faculty Papers

Background: Severe pulmonary embolism (PE) with right heart failure (RHF) has high mortality. To more fully understand PE progression, we evaluated the right ventricle (RV) and pulmonary circulation response to graded PE in an acute PE sheep model.

Methods: Polydextran beads were intravenously administered every 15 minutes in 250 mg doses to adult female sheep (n = 8) until death. Concurrent pulmonary artery (PA) blood flow/pressure was measured. RV pressure-volume (P-V) loops were generated with a conductance catheter. Pulmonary vascular resistance was used to stage PE severity into mild, moderate, and severe groups.

Results: All sheep developed graded RHF. For …