Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Leukocytes As Mediators Of Gut-Brain Communication, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Food allergies

▪ Reactions range from mild/delayed to severe/rapid. ▪ People with mild allergic reactions have increased re-exposure risks. ▪ Cow’s milk allergy tends to manifest with milder allergic reactions.

Cow’s milk allergy (CMA)

▪ CMA has been associated with behavioral and neurological disorders. ▪ How allergic inflammatory signals from the gut reach the brain is unclear

Continuous Consumption Of Whey Protein Affects Motor And Cognitive Functions In A Mouse Model Of Cow’S Milk Hypersensitivity, Geetika Verma

Biomedical Sciences Posters and Presentations

Hypersensitization to a food allergen can occur in the absence of immediate allergic reactions, a condition referred to as asymptomatic sensitization. Using mice asymptomatically sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), we have previously shown that chronic exposure to the allergen results in behavior changes with increased neuroinflammation and cortical demyelination. However, whether allergen avoidance can resolve these pathologies is unknown. Thus, we aimed to compare immunological and behavioral changes in sham- or BLG-sensitized mice with or without the removal of dietary whey after the mice had consumed either a control diet (CTL) or a whey-protein-containing …

Continued Food-Allergen Consumption Exacerbates Beta-Amyloid Accumulation In Allergen-Sensitized Appnl-G-Fmice., Afrina Brishti

Biomedical Sciences Posters and Presentations

Alzheimer’s disease (AD) is the most common neurodegenerative disease, with β-amyloid(Aβ) plaque deposition being one of the hallmark pathologies. However, the etiology of AD remains elusive. While chronic inflammation from recurrent infections or injury seems to contribute to AD development, it is unclear whether atopic diseases, such as allergies, are associated with AD. We previously reported that continuous consumption of a whey protein(WP) -containing diet led to lasting neuro inflammation in C57BL/6J mice that were sensitized but tolerant to a bovine milk allergen, β-lactoglobulin (BLG;Bosd5). Thus, we hypothesized that the persisting neuroinflammation due to repeated allergen consumption would exacerbate AD …

Histamine H3 Receptor Antagonism Mitigates Food-Hypersensitivity-Associated Depressive Behavior And Neuropathology In A Mouse Model Of Cow’S Milk Allergy, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

Background Histamine is best known for causing allergy symptoms, but it also regulates blood-brain barrier permeability1 and oligodendrocyte differentiation2. Thus, brain histamine levels are tightly controlled.

Previous Findings We demonstrated that histamine and histamine H3 receptor (H3R) levels were elevated in a mouse model of cow’s milk allergy (CMA) in association with intracranial mast cell activation, depression-like behaviors, and cortical demyelination3,4.

Gaps in Knowledge In humans, food allergies are often associated with neuropsychiatric disorders5-7, but the involvement of allergy induced histamine in triggering behavioral changes is unclear.

Hypothesis Repeated allergen consumption can lead to central histaminergic dysfunction through H3R, ultimately …

Continuous Consumption Of Whey Protein Maintains Neuroinflammation In A Mouse Model Of Asymptomatic Cow’S Milk Allergy, Geetika Verma

Biomedical Sciences Posters and Presentations

Using a mouse model of cow’s milk allergy (CMA), we previously showed that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG), exhibited anxiety/depression-like behavior and neuroinflammation in the absence of overt anaphylaxis upon allergen exposure

Milk Allergen Increases Intestinal Immune Cells In Association With Neuroinflammation And Behavioral Changes, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Cow’s milk allergy (CMA)

 CMA h as been associated with neurological disorders.

 How allergic inflammatory signals from the gut reach the brain is unclear.

Repeated Allergen Exposure Induces Histaminergic Dysregulation And Depression-Like Behaviors In A Non-Anaphylactic Food Allergy Mouse Model, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Food allergy is often comorbid with neuropsychiatric disorders such as anxiety1,2, depression1,2, OCD3, ADD/ADHD4, and autism5. ➢ The mechanism of how food allergy may impact brain function and behavior in certain allergic individuals has yet to be elucidated.

▪ Mast cells (MCs) are not only the effector cell of the hypersensitivity response but are also important in maintaining brain homeostasis6. ➢ MCs have been implicated in neuropsychiatric and neurodegenerative disorders such as multiple sclerosis7,8.

▪ We have previously found in a mouse model of cow’s milk allergy (CMA) that intracranial MC numbers9 and histamine 3 receptor (H3R)10 increased after …

Cortical Demyelination And Depression-Like Behavior Are Associated With Histaminergic Dysregulation In A Mouse Model Of Peripheral Inflammation, Danielle Germundson-Hermanson

Biomedical Sciences Posters and Presentations

▪ Demyelinating diseases of the central nervous system are increasing in prevalence world-wide1,2 and manifest as motor, behavioral, and/or cognitive defects3 . The etiology and pathophysiology of demyelinating diseases remain unclear.

▪ We have previously observed cortical demyelination in our mouse model of non-anaphylactic cow’s milk allergy4 . The demyelination was associated with depression-like behaviors and region-specific increases in brain histamine and H3 receptor (H3R) levels4,5 .

❖ The brain’s central histaminergic system is tightly controlled and regulates many behaviors. Additionally, signaling through H3R plays a crucial role in oligodendrocyte differentiation, and thus, demyelination and remyelination6 .

▪ We hypothesized …

Understanding The Journey Of Human Prenatal Cd4+ Plzf+ T Cells To The Small Intestine, Tomi Oyedeji Olaniyan

CMC Senior Theses

The fetal immune system has a variety of needs that differ from those of the adult immune system. One such difference is fetal T cell composition and how they migrate from the thymus to peripheral lymphoid organs and mucosal tissue such as the small intestine (SI). Previous research shows that the majority of memory T cells in the prenatal SI are CD4+ PLZF+ T cells but the mechanisms involved in the homing of these cells in the small intestine have not yet been determined. In our experiment, I found evidence to support the claim that IL-7 drives the acquisition of …

Steady-State Regulation Of Secretory Cargo Export And Er Homeostasis By Inositol Trisphosphate Receptors And Penta-Ef-Hand Proteins, Aaron J. Held

Graduate Student Theses, Dissertations, & Professional Papers

Constant protein degradation and turnover necessitates constitutive secretion that delivers the correct mix of nascent proteins to their appropriate subcellular destinations. Cells thus exhibit steady-state secretion and the additional ability to adjust secretory flux, though we lack a clear understanding of this critical process. During secretion, the COPII coat is responsible for providing a balance of actively and passively selected ER cargos to enter the secretory pathway. Furthermore, Ca²⁺ -binding proteins have been implicated in regulating this process in response to Ca²⁺ signals. In Chapter 1, we review the secretory pathway and vesicular trafficking, with a focus on …

Sart-3 Functions To Regulate Germline Sex Determination In C Elegans, Tokiko Furuta, Swathi Arur

Faculty, Staff and Student Publications

Caenorhabditis elegans gene sart-3 was first identified as the homolog of human SART3 ( S quamous cell carcinoma A ntigen R ecognized by T -cells 3). In humans, expression of SART3 is associated with squamous cell carcinoma, thus most of the studies focus on its potential role as a target of cancer immunotherapy (Shichijo et al. 1998; Yang et al. 1999). Furthermore, SART3 is also known as Tip110 (Liu et al. 2002; Whitmill et al. 2016) in the context of HIV virus host activation pathway. Despite these disease related studies, the molecular function of this protein was not revealed until …

Transiently Impaired Endothelial Function During Thyroid Hormone Withdrawal In Differentiated Thyroid Cancer Patients, Li-Ying Hou, Xiao Li, Guo-Qiang Zhang, Chuang Xi, Chen-Tian Shen, Hong-Jun Song, Wen-Kun Bai, Zhong-Ling Qiu, Quan-Yong Luo

Faculty, Staff and Student Publications

PURPOSE: Endothelial dysfunction, which was associated with chronic hypothyroidism, was an early event in atherosclerosis. Whether short-term hypothyroidism following thyroxine withdrawal during radioiodine (RAI) therapy was associated with endothelial dysfunction in patients with differentiated thyroid cancer (DTC) was unclear. Aim of the study was to assess whether short-term hypothyroidism could impair endothelial function and the accompanied metabolic changes in the whole process of RAI therapy.

METHODS: We recruited fifty-one patients who underwent total thyroidectomy surgery and would accept RAI therapy for DTC. We analyzed thyroid function, endothelial function and serum lipids levels of the patients at three time points: the …

Anti-Inflammatory Effects Of Vagus Nerve Stimulation In Pediatric Patients With Epilepsy, Supender Kaur, Nathan R Selden, Alejandro Aballay

Faculty, Staff and Student Publications

INTRODUCTION: The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.

METHODS: Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression …

Gene Expression In Mice With Endothelium-Specific Telomerase Knockout, Zhanguo Gao, Yongmei Yu, Yulin Dai, Zhongming Zhao, Kristin Eckel-Mahan, Mikhail G Kolonin

Faculty, Staff and Student Publications

No abstract provided.

Cytosolic Dna Sensing Protein Pathway Is Activated In Human Hearts With Dilated Cardiomyopathy, Leila Rouhi, Sirisha M Cheedipudi, Benjamin Cathcart, Priyatansh Gurha, Ali J Marian

Faculty, Staff and Student Publications

INTRODUCTION: The genome is constantly exposed to numerous stressors, which induce DNA lesions, including double-stranded DNA breaks (DSBs). DSBs are the most dangerous, as they induce genomic instability. In response to DNA damage, the cell activates nuclear DNA damage response (DDR) and the cytosolic DNA sensing protein (CDSP) pathways, the latter upon release of the DSBs to the cytosol. The CDSP pathway activates NFκB and IRF3, which induce the expression of the pro-inflammatory genes. There is scant data on the activation of the CDSP pathway in human hearts with dilated cardiomyopathy (DCM).

AIM: We aimed to determine expression levels of …

Heterogeneity Of Memory T Cells In Aging, Abhinav Jain, Ines Sturmlechner, Cornelia M Weyand, Jörg J Goronzy

Faculty, Staff and Student Publications

Immune memory is a requisite and remarkable property of the immune system and is the biological foundation of the success of vaccinations in reducing morbidity from infectious diseases. Some vaccines and infections induce long-lasting protection, but immunity to other vaccines and particularly in older adults rarely persists over long time periods. Failed induction of an immune response and accelerated waning of immune memory both contribute to the immuno-compromised state of the older population. Here we review how T cell memory is influenced by age. T cell memory is maintained by a dynamic population of T cells that are heterogeneous in …

Gankyrin-Mediated Interaction Between Cancer Cells And Tumor-Associated Macrophages Facilitates Prostate Cancer Progression And Androgen Deprivation Therapy Resistance, Guang Peng, Chao Wang, Hongru Wang, Min Qu, Keqin Dong, Yongwei Yu, Yuquan Jiang, Sishun Gan, Xu Gao

Faculty, Staff and Student Publications

Increasing evidence reveals that the interaction between tumor cells and tumor-associated macrophages (TAMs) facilitates the progression of prostate cancer, but the related mechanisms remained unclear. This study determined how gankyrin, a component of the 19S regulatory complex of the 26S proteasome, regulates the progression and androgen deprivation therapy (ADT) resistance of prostate cancer through tumor cell-TAM interactions.

Protein Translation Paradox: Implications In Translational Regulation Of Aging, Harper S Kim, Andrew M Pickering

Faculty, Staff and Student Publications

Protein translation is an essential cellular process playing key roles in growth and development. Protein translation declines over the course of age in multiple animal species, including nematodes, fruit flies, mice, rats, and even humans. In all these species, protein translation transiently peaks in early adulthood with a subsequent drop over the course of age. Conversely, lifelong reductions in protein translation have been found to extend lifespan and healthspan in multiple animal models. These findings raise the protein synthesis paradox: age-related declines in protein synthesis should be detrimental, but life-long reductions in protein translation paradoxically slow down aging and prolong …

Next-Generation Ctla-4 Targeting Molecules And Combination Therapy: Promising Strategies For Improving Cancer Immunotherapy, Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand

Faculty, Staff and Student Publications

Radiation therapy and anti-CTLA-4 combination therapy can induce meaningful responses in some patients. Adding CD40 may provide additional benefit. Next-generation anti-CTLA-4 antibodies, such as botensilimab, are showing promise in clinical trials. Combining botensilimab with RT and/or CD40 agonist may offer additional benefits for challenging tumor types.

Dietary Whey Protein Increases Brain Leukocytes In Mice Regardless Of Their Hypersensitivity Status, Dilini Ekanayake

Biomedical Sciences Posters and Presentations

Cow’s milk allergy (CMA) often manifests as milder reactions and may be linked to neurological problems. Previously, we demonstrated that C57BL/6J mice sensitized to a bovine whey allergen, β-lactoglobulin (BLG, Bos d 5), moderately increased BLG-specific IgE levels and exhibited behavioral changes without severe allergic reactions. When these non-anaphylactic CMA mice were placed on a whey-protein (WP)-containing diet for 2 weeks to simulate continuous dairy consumption, we found neuropathology indicative of neuroinflammation and cortical demyelination. Since immune cells migrate to the central nervous system (CNS) and promote neuroinflammation in demyelinating conditions such as multiple sclerosis, we hypothesized that the number …

Investigating The Potential Role Of Akkermansia Muciniphila Supplementation In Neuroinflammation: A Progress Report, Geetika Verma

Biomedical Sciences Posters and Presentations

Gut bacteria are important for proper development and function of the host immune system (1). Recent studies have provided association of altered microbiome in both food allergy and neuropsychiatric disorders (2, 3) indicating potential role of microbiome in regulating Gut-Brain-Axis. Akkermansia muciniphila belongs to the phylum Verrucomicrobia, is a commensal mucin degrading bacterial species (4). A. muciniphila protects the gut barrier by facilitating host mucus production. Since patients with food allergy have increased gut permeability, protection of intestinal barrier by increased mucus production may be beneficial in preventing allergen and pathogen infiltrations, hence, minimizing inflammation. A. muciniphila is well known …

Early-Phase Drive To The Precursor Pool: Chloroviruses Dive Into The Deep End Of Nucleotide Metabolism, David Dunigan, Irina Agarkova, Ahmed Esmael, Sophie Alvarez, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Viruses face many challenges on their road to successful replication, and they meet those challenges by reprogramming the intracellular environment. Two major issues challenging Paramecium bursaria chlorella virus 1 (PBCV-1, genus Chlorovirus, family Phycodnaviridae) at the level of DNA replication are (i) the host cell has a DNA G+C content of 66%, while the virus is 40%; and (ii) the initial quantity of DNA in the haploid host cell is approximately 50 fg, yet the virus will make approximately 350 fg of DNA within hours of infection to produce approximately 1000 virions per cell. Thus, the quality and quantity of …

The Persistence And Stabilization Of Auxiliary Genes In The Human Skin Virome, Ema H. Graham, Wesley A. Tom, Alison C. Neujahr, Michael Adamowicz, Jennifer Clarke, Joshua R. Herr, Samodha C. Fernando

Nebraska Center for Virology: Faculty Publications

Background The human skin contains a diverse microbiome that provides protective functions against environmental pathogens. Studies have demonstrated that bacteriophages modulate bacterial community composition and facilitate the transfer of host-specific genes, potentially influencing host cellular functions. However, little is known about the human skin virome and its role in human health. Especially, how viral-host relationships influence skin microbiome structure and function is poorly understood.

Results Population dynamics and genetic diversity of bacteriophage communities in viral metagenomic data collected from three anatomical skin locations from 60 subjects at five different time points revealed that cutaneous bacteriophage populations are mainly composed of …

Characterizing The Effects Of Antiandrogens And Senolytics To Enhance The Therapeutic Response To Castration-Resistant Prostate Cancer, Justin M. Silverman

Theses and Dissertations

Prostate cancer is the most frequently diagnosed cancer in males and the second most common cause of cancer deaths. Androgen deprivation therapy, whether through surgical or chemical castration, is the mainstay for treatment of advanced prostate cancer; however, despite an initial response, most patients eventually develop a progressive PSA rise, and castration- sensitive prostate cancer gives rise to castration-resistant prostate cancer. The standard of care therapy includes the antiandrogens such as enzalutamide and abiraterone acetate as well as the microtubule poison, docetaxel, and various immunotherapies; however, while prostate cancer research is progressing, there continues to be a compelling need for …

Vulnerability And Adaptation Of Neocortical Neuron Subtypes In Models Of Concussive Traumatic Brain Injury And Multiple Sclerosis, Alan C. Harris Jr.

Theses and Dissertations

The pathognomonic sequela of traumatic brain injury is traumatic axonal injury, the

burden of which correlates with less favorable outcomes. Elucidation of

the intrinsic variables that endow delineated neuronal subgroups and microanatomical domains with outsized vulnerability to injury represents a critical domain of inquiry toward the successful translation of disease-modifying therapeutics. To this end, we studied mild traumatic brain injury (mTBI) within the central fluid percussion model to examine the consequences of mTBI on the morphology and functional integrity of the axon initial segment (AIS) and the relative contributions to network homeostasis mediated by distinct populations of inhibitory interneurons. One …

Identification Of Microbiological Factors Associated With Periodontal Health Disparities, Bing-Yan Wang, Aize Cao, Meng-Hsuan Ho, Derek Wilus, Sally Sheng, Hsiu-Wan Meng, Elissa Guerra, Jianming Hong, Hua Xie

Faculty, Staff and Student Publications

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 …

Association Of Cyclooxygenase-2 Expression With Endoplasmic Reticulum Stress And Autophagy In Triple-Negative Breast Cancer, Haechan Lee, Sungwook Jung, Gyungyub Gong, Bora Lim, Hee Jin Lee

Faculty, Staff and Student Publications

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. …

Risk Factors Associated With Severe Clostridioides Difficile Infection In Patients With Cancer, Denise Marie A Francisco, Liangliang Zhang, Ying Jiang, Adilene Olvera, Javier Adachi, Eduardo Yepez Guevara, Samuel L Aitken, Kevin W Garey, Christine B Peterson, Kim-Anh Do, Ryan Dillon, Engels N Obi, Robert Jenq, Pablo C Okhuysen

Faculty, Staff and Student Publications

INTRODUCTION: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer.

METHODS: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome …

Associative Learning Contributes To The Persistence Of Fatigue-Like Behavior In Male Mice In A Model Of Cancer Survivorship, Elisabeth G Vichaya, Josephine K Darpolor, Phillip S Gross, Jessica M Molkentine, Daniel W Vermeer, Paola D Vermeer, John H Lee, Cullen M Taniguchi, Robert Dantzer

Faculty, Staff and Student Publications

Persistent fatigue is a debilitating side effect that impacts a significant proportion of cancer survivors for which there is not yet an FDA-approved treatment. While certainly a multi-factorial problem, persistent fatigue could be due, in part, to associations learned during treatment. Therefore, we sought to investigate the role of associative learning in the persistence of fatigue using a preclinical model of cancer survivorship. For this purpose, we used a murine model of human papilloma virus-related head and neck cancer paired with a curative regimen of cisplatin-based chemoradiation in male C57BL/6J mice. Fatigue-like behavior was assessed by measuring variations in voluntary …

Sparse Tree-Based Clustering Of Microbiome Data To Characterize Microbiome Heterogeneity In Pancreatic Cancer, Yushu Shi, Liangliang Zhang, Kim-Anh Do, Robert Jenq, Christine B Peterson

Faculty, Staff and Student Publications

There is a keen interest in characterizing variation in the microbiome across cancer patients, given increasing evidence of its important role in determining treatment outcomes. Here our goal is to discover subgroups of patients with similar microbiome profiles. We propose a novel unsupervised clustering approach in the Bayesian framework that innovates over existing model-based clustering approaches, such as the Dirichlet multinomial mixture model, in three key respects: we incorporate feature selection, learn the appropriate number of clusters from the data, and integrate information on the tree structure relating the observed features. We compare the performance of our proposed method to …