Medical Pathology Commons^™

The Low Abundance Of Cpg In The Sars-Cov-2 Genome Is Not An Evolutionarily Signature Of Zap, Ali Afrasiabi, Hamid Alinejad-Rokny, Azad Khosh, Mostafa Rahnama, Nigel Lovell, Zhenming Xu, Diako Ebrahimi

Plant Pathology Faculty Publications

The zinc finger antiviral protein (ZAP) is known to restrict viral replication by binding to the CpG rich regions of viral RNA, and subsequently inducing viral RNA degradation. This enzyme has recently been shown to be capable of restricting SARS-CoV-2. These data have led to the hypothesis that the low abundance of CpG in the SARS-CoV-2 genome is due to an evolutionary pressure exerted by the host ZAP. To investigate this hypothesis, we performed a detailed analysis of many coronavirus sequences and ZAP RNA binding preference data. Our analyses showed neither evidence for an evolutionary pressure acting specifically on CpG …

Noncoding-Rna-Based Therapeutics With An Emphasis On Prostatic Carcinoma-Progress And Challenges., Victor E. Nava, Pin-Yu Perera, Nirbhay Kumar, Maneesh Jain

Pathology Faculty Publications

Noncoding RNAs (ncRNAs) defy the central dogma by representing a family of RNA molecules that are not translated into protein but can convey information encoded in their DNA. Elucidating the exact function of ncRNA has been a focus of discovery in the last decade and remains challenging. Nevertheless, the importance of understanding ncRNA is apparent since these molecules regulate gene expression at the transcriptional and post-transcriptional level exerting pleiotropic effects critical in development, oncogenesis, and immunity. NcRNAs have been referred to as "the dark matter of the nucleus", and unraveling their role in physiologic and pathologic processes will provide vast …

The Role Of Decorin Proteoglycan In Mitophagy., Thomas Neill, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proteoglycans are emerging as critical regulators of intracellular catabolism. This rise in prominence has transformed our basic understanding and alerted us to the existence of non-canonical pathways, independent of nutrient deprivation, that potently control the autophagy downstream of a cell surface receptor. As a member of the small leucine-rich proteoglycan gene family, decorin has single-handedly pioneered the connection between extracellular matrix signaling and autophagy regulation. Soluble decorin evokes protracted endothelial cell autophagy via Peg3 and breast carcinoma cell mitophagy via mitostatin by interacting with VEGFR2 or the MET receptor tyrosine kinase, respectively. In this paper, we give a mechanistic perspective …

Mir-196a Upregulation Contributes To Gefitinib Resistance Through Inhibiting Gltp Expression, Bing-Jie Liu, Fang-Fang Li, Yun-Xia Xie, Chong-Yuan Fan, Wen-Jing Liu, Jian-Ge Qiu, Bing-Hua Jiang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Tyrosine kinase inhibitor (TKI) therapy has greatly improved lung cancer survival in patients with epidermal growth factor receptor (EGFR) mutations. However, the development of TKI-acquired resistance is the major problem to be overcome. In this study, we found that miR-196a expression was greatly induced in gefitinib-resistant lung cancer cells. To understand the role and mechanism of miR-196a in TKI resistance, we found that miR-196a-forced expression alone increased cell resistance to gefitinib treatment in vitro and in vivo by inducing cell proliferation and inhibiting cell apoptosis. We identified the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) bound to the …

A Summary Of The Inaugural Who Classification Of Pediatric Tumors: Transitioning From The Optical Into The Molecular Era., Stefan M Pfister, Miguel Reyes-Múgica, John K C Chan, Henrik Hasle, Alexander J Lazar, Sabrina Rossi, Andrea Ferrari, Jason A Jarzembowski, Kathy Pritchard-Jones, D. Ashley Hill, Thomas S Jacques, Pieter Wesseling, Dolores H López Terrada, Andreas Von Deimling, Christian P Kratz, Ian A Cree, Rita Alaggio

Pathology Faculty Publications

Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on "blastomas," which variably recapitulate the morphologic maturation of organs from …

The Impact Of Age And Sex On Aortic Dissection Outcomes: A True Controversy Or Lack Of Standardization?, Erin F Mccaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B Fitzpatrick, Sanjana Gupta, Noah F Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K Ramdial, Erna Forgó, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A Khader, Sean C Bendall, Matt Van De Rijn, Daniel Kalman, Deepak Kaushal, Robert L Hunter, Niaz Banaei, Adrie J C Steyn, Purvesh Khatri, Michael Angelo

Faculty, Staff and Student Publications

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1

Reactive Oxygen Species Reprogram Macrophages To Suppress Antitumor Immune Response Through The Exosomal Mir-155-5p/Pd-L1 Pathway, Xiang Li, Shaomin Wang, Wei Mu, Jennifer Barry, Anna Han, Richard L Carpenter, Bing-Hua Jiang, Stephen C Peiper, M G Mahoney, A E Aplin, Hong Ren, Jun He

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Cancer cells have an imbalance in oxidation-reduction (redox) homeostasis. Understanding the precise mechanisms and the impact of the altered redox microenvironment on the immunologic reaction to tumors is limited.

Methods: We isolated exosomes from ovarian cancer cells through ultracentrifuge and characterized by Western-blots and Nanoparticle Tracking Analysis. 2D, 3D-coculture tumor model, and 3D live cell imaging were used to study the interactions between tumor cells, macrophages and CD3 T cells in vitro. The role of exosomal miR-155-5p in tumor growth was evaluated in xenograft nude mice models and immune-competent mice models. Flow cytometry and flow sorting were used to …

Microbial Cell Factory Of Baccatin Iii Preparation In Escherichia Coli By Increasing Dbat Thermostability And In Vivo Acetyl-Coa Supply, Jia-Jun Huang, Tao Wei, Zhi-Wei Ye, Qian-Wang Zheng, Bing-Hua Jiang, Wen-Feng Han, An-Qi Ye, Pei-Yun Han, Li-Qiong Guo, Jun-Fang Lin

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Given the rapid development of genome mining in this decade, the substrate channel of paclitaxel might be identified in the near future. A robust microbial cell factory with gene dbat, encoding a key rate-limiting enzyme 10-deacetylbaccatin III-10-O-transferase (DBAT) in paclitaxel biosynthesis to synthesize the precursor baccatin III, will lay out a promising foundation for paclitaxel de novo synthesis. Here, we integrated gene dbat into the wild-type Escherichia coli BW25113 to construct strain BWD01. Yet, it was relatively unstable in baccatin III synthesis. Mutant gene dbat S189V with improved thermostability was screened out from a semi-rational mutation library …

Opa1 Modulates Mitochondrial Ca 2+ Uptake Through Er-Mitochondria Coupling, Benjamín Cartes-Saavedra, Josefa Macuada, Daniel Lagos, Duxan Arancibia, María E Andrés, Patrick Yu-Wai-Man, György Hajnóczky, Verónica Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Autosomal Dominant Optic Atrophy (ADOA), a disease that causes blindness and other neurological disorders, is linked to OPA1 mutations. OPA1, dependent on its GTPase and GED domains, governs inner mitochondrial membrane (IMM) fusion and cristae organization, which are central to oxidative metabolism. Mitochondrial dynamics and IMM organization have also been implicated in Ca2+ homeostasis and signaling but the specific involvements of OPA1 in Ca2+ dynamics remain to be established. Here we studied the possible outcomes of OPA1 and its ADOA-linked mutations in Ca2+ homeostasis using rescue and overexpression strategies in Opa1-deficient and wild-type murine embryonic fibroblasts (MEFs), respectively and in …

Childhood Trauma And Chronic Disease, Breanna Urena

Graduate Research Projects

No abstract provided.

Transcatheter Aortic Valve Replacement (Tavr), Ashlyn Case

Medical Imaging Senior Posters

Title of Poster: Transcatheter aortic valve replacement (TAVR) Student Researcher: Ashlyn Case Faculty Advisor: Loraine D. Zelna, M.S., R.T. (R)(MR) Internship Mentor: Stephanie Jugus, B.S., R.T., RCIS Internship Site: Cardiac Cath, Regional Hospital of Scranton, Scranton, PA Abstract Transcatheter aortic valve replacement

(TAVR) is a minimally invasive procedure option for patients suffering from severe aortic stenosis. The procedure is quickly evolving and is crucial to individuals who cannot receive open heart procedures. Aortic stenosis occurs when the aortic valve (valve connecting the aorta to the left ventricle) of the heart is unable to fully open. This is detrimental to a …

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

Ahcc® Supplementation To Support Immune Function To Clear Persistent Human Papillomavirus Infections, Judith A Smith, Anjali A Gaikwad, Lata Mathew, Barbara Rech, Jonathan P Faro, Joseph A Lucci, Yu Bai, Randall J Olsen, Teresa T Byrd

Faculty, Staff and Student Publications

OBJECTIVE: To determine the efficacy, safety, and durability of the use of AHCC supplementation for 6 months to support the host immune system to clear high-risk human papillomavirus (HPV) infections. The AHCC supplement is a proprietary, standardized extract of cultured lentinula edodes mycelia (AHCC

STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study (CTN: NCT02405533) in 50 women over 30 years of age with confirmed persistent high-risk HPV infections for greater than 2 years. Patients were randomized to placebo once daily for 12 months (N = 25) or AHCC 3-g supplementation by mouth once daily on empty stomach for 6 …

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …

Clinical Pearls To Diagnosing Lyme Arthritis, Chandelle Keller

Capstone Showcase

Arthritis is one of the most common long term sequelae of Lyme disease infection in humans. Although the pathophysiology for Lyme arthritis is not concretely understood, there are several key features that are helpful in diagnosing Lyme disease as the culprit for the arthritic symptoms that an individual is experiencing. With a thorough history of an individuals’ age, geographic location, recent travel history and common outdoor recreational activities engaged in, a differential can be narrowed down. With the knowledge of how various arthritides present in the body, along with the use of diagnostic testing with ELISA and Western immunoblot, any …

Treatment Of Hypothyroidism: Desiccated Thyroid Extract, Aimee Fong

Capstone Showcase

The treatment of hypothyroidism with Levothyroxine (T4) has been well studied and FDA approved. However, many patients continue to have signs and symptoms of hypothyroidism while on Levothyroxine treatment despite reaching appropriate thyroid levels. An additional thyroid treatment known as desiccated thyroid extract (DTE) is made from dried pig thyroid glands and is advertised as a “natural” alternative to Levothyroxine. Despite lack of FDA approval and studies surrounding DTE, clinicians have prescribed DTE to patients, many of whom reported relief of their symptoms. The following poster highlights the approach to the treatment of hypothyroidism with Levothyroxine and DTE and outlines …

Anthracyclines Attenuate The Nrf1-Mediated Bounce-Back Response, Bader Albalawi

Theses and Dissertations

Proteasome inhibitors, such as carfilzomib, are FDA-approved to treat multiple myeloma and mantle cell lymphoma. Unfortunately, proteasome inhibitors have only produced clinically significant results in patients with hematologic cancers, despite their predicted pan-cancer utility, and even hematologic cancer types frequently show intrinsic and acquired resistance.

One proposed mechanism responsible for the proteasome inhibitors' shortcomings is the NRF1-mediated bounce-back response. Identification of drugs that can potentiate the action of proteasome inhibitors could overcome resistance in patients with hematologic cancers and expand proteasome inhibitors' use to treat solid tumors. Our previous studies have identified anthracyclines as potential compounds that interfere with the …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …