Medical Pathology Commons^™

Chronic Wasting Disease: State Of The Science, Jason C Bartz, Rebeca Benavente, Byron Caughey, Sonja Christensen, Allen Herbst, Edward A Hoover, Candace K Mathiason, Debbie Mckenzie, Rodrigo Morales, Marc D Schwabenlander, Daniel P Walsh, The Nc North American Interdisciplinary Chronic Wasting Disease Research Consortium Members

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervid species, both free-ranging and captive populations. As the geographic range continues to expand and disease prevalence continues to increase, CWD will have an impact on cervid populations, local economies, and ecosystem health. Mitigation of this "wicked" disease will require input from many different stakeholders including hunters, landowners, research biologists, wildlife managers, and others, working together. The NC1209 (North American interdisciplinary chronic wasting disease research consortium) is composed of scientists from different disciplines involved with investigating and managing CWD. Leveraging this broad breadth of expertise, the Consortium has created a state-of-the-science …

Child Deaths Caused By Klebsiella Pneumoniae In Sub-Saharan Africa And South Asia: A Secondary Analysis Of Child Health And Mortality Prevention Surveillance (Champs) Data., Jennifer Verani, Dianna Blau, Emily Gurley, Victor Akelo, Nega Assefa, Vicky Baillie, Quique Bassat, Mussie Berhane, James Bunn, R Gunturu

Pathology, East Africa

Background; Klebsiella pneumoniae is an important cause of nosocomial and community-acquired pneumonia and sepsis in children, and antibiotic-resistant K pneumoniae is a growing public health threat. We aimed to characterize child mortality associated with this pathogen in seven high-mortality settings.

Methods; We analysed Child Health and Mortality Prevention Surveillance (CHAMPS) data on the causes of deaths in children younger than 5 years and stillbirths in sites located in seven countries across sub-Saharan Africa (Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa) and south Asia (Bangladesh) from Dec 9, 2016, to Dec 31, 2021. CHAMPS sites conduct active surveillance for …

Non‐V600e Braf Mutation In Hairy Cell Leukemia Variant, Anjanaa Vijayanarayanan, Sa A Wang, Sofia Garces, Karan Saluja, L Jeffrey Medeiros, Beenu Thakral

Faculty, Staff and Student Publications

No abstract provided.

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Multivalent Epigraph Hemagglutinin Vaccine Protects Against Influenza B Virus In Mice, Erika M. Petro-Turnquist, Brigette Corder Kampfe, Amber Gadeken, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza B virus is a respiratory pathogen that contributes to seasonal epidemics, accounts for approximately 25% of global influenza infections, and can induce severe disease in young children. While vaccination is the most commonly used method of preventing influenza infections, current vaccines only induce strain-specific responses and have suboptimal efficacy when mismatched from circulating strains. Further, two influenza B virus lineages have been described, B/Yamagatalike and B/Victoria-like, and the limited cross-reactivity between the two lineages provides an additional barrier in developing a universal influenza B virus vaccine. Here, we report a novel multivalent vaccine using computationally designed Epigraph hemagglutinin proteins …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Enhancing Mitosis Quantification And Detection In Meningiomas With Computational Digital Pathology, Hongyan Gu, Chunxu Yang, Issa Al-Kharouf, Shino Magaki, Nelli Lakis, Christopher Kazu Williams, Sallam Mohammad Alrosan, Ellie Kate Onstott, Wenzhong Yan, Negar Khanlou, Inma Cobos, Xinhai Robert Zhang, Neda Zarrin-Khameh, Harry V Vinters, Xiang Anthony Chen, Mohammad Haeri

Faculty, Staff and Student Publications

Mitosis is a critical criterion for meningioma grading. However, pathologists' assessment of mitoses is subject to significant inter-observer variation due to challenges in locating mitosis hotspots and accurately detecting mitotic figures. To address this issue, we leverage digital pathology and propose a computational strategy to enhance pathologists' mitosis assessment. The strategy has two components: (1) A depth-first search algorithm that quantifies the mathematically maximum mitotic count in 10 consecutive high-power fields, which can enhance the preciseness, especially in cases with borderline mitotic count. (2) Implementing a collaborative sphere to group a set of pathologists to detect mitoses under each high-power …

Preclinical Repurposing Of Sitagliptin As A Drug Candidate For Colorectal Cancer By Targeting Cd24/Ctnnb1/Sox4-Centered Signaling Hub, Jing-Wen Shih, Alexander T H Wu, Ntlotlang Mokgautsi, Po-Li Wei, Yan-Jiun Huang

Faculty, Staff and Student Publications

Despite significant advances in treatment modalities, colorectal cancer (CRC) remains a poorly understood and highly lethal malignancy worldwide. Cancer stem cells (CSCs) and the tumor microenvironment (TME) have been shown to play critical roles in initiating and promoting CRC progression, metastasis, and treatment resistance. Therefore, a better understanding of the underlying mechanisms contributing to the generation and maintenance of CSCs is crucial to developing CSC-specific therapeutics and improving the current standard of care for CRC patients. To this end, we used a bioinformatics approach to identify increased CD24/SOX4 expression in CRC samples associated with poor prognosis. We also …

A Rare Case Of A Giant Cell Tumor Of The Peroneal Tendon Sheath, Francois M. Lokenye Dpm, Breana Marine Dpm, Orlexia Thomas Dpm, Mariam Kamil Bs

Posters

This case report discusses a 31-year-old male with TGCT in the peroneal tendon sheath, detailing clinical and radiological features.

his study explores the surgical interventions, diagnostic challenges, treatment options, and outcomes of TGCT, emphasizing its consideration in the differential diagnoses of painful foot and ankle masses.

Extending The Gift—Utilizing Residual Human Anatomical Materials For Training Pathologists' Assistants In Surgical Pathology Techniques, Kerwin M. Kolheffer, Lauren Yoho, Matthew Myers, Ismail El Moudden

Department of Pathology & Anatomy Faculty Publications

This study investigates the effectiveness of using residual human anatomical materials, obtained from a gross anatomy course, for training Pathologists' Assistant (PathA) students in surgical pathology techniques. We utilized two surveys to assess the perceived efficacy of this approach: one survey targeted PathA students to evaluate their training experiences with both human and animal tissues, while the other assessed the impact of specimen collection on the educational experiences of gross anatomy course students.

Insights Into The Assembly And Regulation Of The Bacterial Divisome, Todd A Cameron, William Margolin

Faculty, Staff and Student Publications

The ability to split one cell into two is fundamental to all life, and many bacteria can accomplish this feat several times per hour with high accuracy. Most bacteria call on an ancient homologue of tubulin, called FtsZ, to localize and organize the cell division machinery, the divisome, into a ring-like structure at the cell midpoint. The divisome includes numerous other proteins, often including an actin homologue (FtsA), that interact with each other at the cytoplasmic membrane. Once assembled, the protein complexes that comprise the dynamic divisome coordinate membrane constriction with synthesis of a division septum, but only after overcoming …

Quantification Of Gastric Muscle Interstitial Cells Of Cajal In Individuals With And Without Gastroparesis: A Pilot Study, Shazia Rashid, Michelle Neice, Hailey Canezaro, Victoria Andrus, Maryam Mubashir, Syed Musa Raza, James Traylor, Hidehiro Takei, Qiang Cai

Faculty, Staff and Student Publications

No abstract provided.

Rising Prevalence Of Mild Chronic Gastritis In Children: A Single Center Experience, Rohit Josyabhatla, Mary Lauren Wood, Amber Gafur, Nina Tatevian, Amanda S Tchakarov, Syed Shahrukh Hashmi, Jon Marc Rhoads, Melissa Renee Van Arsdall

Faculty, Staff and Student Publications

OBJECTIVES AND METHODS: We analyzed upper endoscopic and histological findings in 3 cohorts of children undergoing upper gastrointestinal endoscopy over a 10-year period. Five hundred seventy-nine patients were identified, with 244 (42%), 199 (35%), and 136 (23%) in the 2011, 2015, and 2019 cohorts, respectively. The most common symptoms and signs were abdominal pain, vomiting, failure to thrive, and diarrhea.

RESULTS: The number of patients who had histological evidence of chronic gastritis increased from 2011 (n = 70, 29%) to 2015 (n = 106, 53%) and 2019 (n = 92, 68%;

CONCLUSIONS: There has been a significant rise in the …

Complete Pathologic Response With Pembrolizumab And Enfortumab Vedotin In Urothelial Carcinoma Of The Upper Urinary Tract, Kok Hoe Chan, Tung Shu, Majd Al Shaarani, Putao Cen

Faculty, Staff and Student Publications

Urothelial carcinoma of the upper urinary tract (UTUC) presents a significant clinical challenge, often requiring aggressive surgical intervention for optimal management. We present a case of an 84-year-old woman with recurrent high-grade papillary UTUC of the left renal pelvis, refractory to prior endourologic interventions, who underwent neoadjuvant treatment with pembrolizumab and enfortumab vedotin (Pembro/EV) due to contraindications to cisplatin therapy. Following a favorable response to neoadjuvant therapy, the patient underwent laparoscopic left radical nephroureterectomy, achieving a pathologic complete response. We discuss the utility of Pembro/EV in the perioperative management of patients with UTUC, particularly in those ineligible for cisplatin-based therapy. …

Efficient Classification Of Very High Resolution Images, Mohammad I. Nouyed

Graduate Theses, Dissertations, and Problem Reports (ETD)

In recent decades, deep learning approaches have shown significant improvement in various image understanding tasks. However, analysis of high-resolution images remains a major challenge. In this work, we address the challenge of very high-resolution histopathological image (VHRHI) classification using a new information-theoretic discriminative patch selection approach. We show results on a high-resolution image dataset, namely, gigapixel whole slide tissue images for cancer tumors. Then we address how to efficiently classify challenging histopathology images, such as gigapixel whole-slide images for cancer diagnostics with image-level annotation. These ``weak labels'' are applied throughout the image but describe tumor regions of variable sizes and …

Exosome Shedding Is Concordant With Objective Treatment Response Rate And Stratifies Time To Progression In Treatment Naïve, Non-Resectable Hepatocellular Carcinoma, Kelley G. Núñez, Dorota Wyczechowska, Mina Hibino, Tyler Sandow, Juan Gimenez, Ali R. Koksal, Yucel Aydin, Srikanta Dash, Ari J. Cohen, Paul T. Thevenot

School of Medicine Faculty Publications

Translational strategies to characterize and monitor extracellular vesicles such as exosome (EX) shedding and the clinical impact of this data within hepatocellular carcinoma (HCC) remains unclear. In this study, EX shedding was assessed in early-stage HCC and evaluated as a stratification factor for time to progression (TTP) following first-cycle liver-directed therapy (LDT). Plasma EXs were isolated from HCC patients undergoing LDT using ultracentrifugation. Purified EXs were stained using markers CD9 and CD63 and quantified using an ImageStreamX flow cytometer. Circulating EXs expressing CD9 were isolated at 10-fold higher levels compared to CD63. The intensity of CD9+ EX shedding following LDT …

Novel Insights Into The Pathogenesis Of Human Post-Primary Tuberculosis From Archival Material Of The Pre-Antibiotic Era, 1931-1947, Syeda Mariam Riaz, Kurt Hanevik, Lars Helgeland, Lisbet Sviland, Robert L Hunter, Tehmina Mustafa

Faculty, Staff and Student Publications

OBJECTIVES: Primary and post-primary tuberculosis (TB) are distinct entities. The aim of this study was to study the histopathology of primary and post-primary TB by using the unique human autopsy material from the pre-antibiotic era, 1931-1947.

MATERIAL AND METHODS: Autopsy data were collected from the autopsy journals, and the human tissue was collected from the pathology archives at the Department of Pathology, the Gades Institute.

RESULTS: Histological presentations of TB lesions showed great diversity within a single lung. Post-primary TB starts as a pneumonia forming early lesions, characterized by the infiltration of foamy macrophages containing mycobacterial antigens within alveoli, and …

An Efficacy And Safety Evaluation Of Montelukast + Fluticasone Propionate Vs Fluticasone Propionate In The Treatment Of Cough Variant Asthma In Children: A Meta-Analysis, Zhengbo Wei, Sheng Li

Faculty, Staff and Student Publications

PURPOSE: This study aimed to evaluate the efficacy and safety of montelukast (Mon) + fluticasone propionate (Flu) versus Flu in the treatment of cough variant asthma (CVA) in children.

METHODS: Eligible documents were selected from various databases. Weighted mean difference (WMD) and 95% confidence interval (CI) were used to evaluate continuous variables, and categorical variables were evaluated using risk ratio (RR) and 95% CI. Heterogeneity analysis was performed using Cochran's Q test and I

RESULTS: Nine studies were included, and Flu + Mon was found to significantly improve the total effective rate and reduce cough recurrence compared to Flu. The …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

Atm Deficiency Confers Specific Therapeutic Vulnerabilities In Bladder Cancer, Yuzhen Zhou, Judit Börcsök, Elio Adib, Sophia C. Kamran, Alexander J. Neil, Konrad Stawiski, Dory Freeman, Dag Rune Stormoen, Zsofia Sztupinszki, Amruta Samant, Amin Nassar, Raie T. Bekele, Timothy Hanlon, Henkel Valentine, Ilana Epstein, Bijaya Sharma, Kristen Felt, Philip Abbosh, Chin-Lee Wu, Jason A. Efstathiou, David T. Miyamoto, William Anderson, Zoltan Szallasi, Kent W. Mouw

Einstein Health Papers

Ataxia-telangiectasia mutated (ATM) plays a central role in the cellular response to DNA damage and ATM alterations are common in several tumor types including bladder cancer. However, the specific impact of ATM alterations on therapy response in bladder cancer is uncertain. Here, we combine preclinical modeling and clinical analyses to comprehensively define the impact of ATM alterations on bladder cancer. We show that ATM loss is sufficient to increase sensitivity to DNA-damaging agents including cisplatin and radiation. Furthermore, ATM loss drives sensitivity to DNA repair-targeted agents including poly(ADP-ribose) polymerase (PARP) and Ataxia telangiectasia and Rad3 related (ATR) inhibitors. ATM loss …

Inflammation In The Tumor-Adjacent Lung As A Predictor Of Clinical Outcome In Lung Adenocarcinoma, Igor Dolgalev, Hua Zhou, Nina Murrell, Hortense Le, Theodore Sakellaropoulos, Nicolas Coudray, Kelsey Zhu, Varshini Vasudevaraja, Anna Yeaton, Chandra Goparaju, Yonghua Li, Imran Sulaiman, Jun-Chieh J Tsay, Peter Meyn, Hussein Mohamed, Iris Sydney, Tomoe Shiomi, Sitharam Ramaswami, Navneet Narula, Ruth Kulicke, Fred P Davis, Nicolas Stransky, Gromoslaw A Smolen, Wei-Yi Cheng, James Cai, Salman Punekar, Vamsidhar Velcheti, Daniel H Sterman, J T Poirier, Ben Neel, Kwok-Kin Wong, Luis Chiriboga, Adriana Heguy, Thales Papagiannakopoulos, Bettina Nadorp, Matija Snuderl, Leopoldo N Segal, Andre L Moreira, Harvey I Pass, Aristotelis Tsirigos

Faculty, Staff and Student Publications

Approximately 30% of early-stage lung adenocarcinoma patients present with disease progression after successful surgical resection. Despite efforts of mapping the genetic landscape, there has been limited success in discovering predictive biomarkers of disease outcomes. Here we performed a systematic multi-omic assessment of 143 tumors and matched tumor-adjacent, histologically-normal lung tissue with long-term patient follow-up. Through histologic, mutational, and transcriptomic profiling of tumor and adjacent-normal tissue, we identified an inflammatory gene signature in tumor-adjacent tissue as the strongest clinical predictor of disease progression. Single-cell transcriptomic analysis demonstrated the progression-associated inflammatory signature was expressed in both immune and non-immune cells, and cell …

Pericentrin Deficiency In Smooth Muscle Cells Augments Atherosclerosis Through Hsf1-Driven Cholesterol Biosynthesis And Perk Activation, Suravi Majumder, Abhijnan Chattopadhyay, Jamie M Wright, Pujun Guan, L Maximilian Buja, Callie S Kwartler, Dianna M Milewicz

Faculty, Staff and Student Publications

Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is caused by biallelic loss-of-function variants in pericentrin (PCNT), and premature coronary artery disease (CAD) is a complication of the syndrome. Histopathology of coronary arteries from patients with MOPDII who died of CAD in their 20s showed extensive atherosclerosis. Hyperlipidemic mice with smooth muscle cell-specific (SMC-specific) Pcnt deficiency (PcntSMC-/-) exhibited significantly greater atherosclerotic plaque burden compared with similarly treated littermate controls despite similar serum lipid levels. Loss of PCNT in SMCs induced activation of heat shock factor 1 (HSF1) and consequently upregulated the expression and activity of HMG-CoA reductase (HMGCR), the rate-limiting enzyme …

Comparative Analysis Of Swine Antibody Responses Following Vaccination With Live-Attenuated And Killed African Swine Fever Virus Vaccines, Hung Q. Luong, Huong T. L. Lai, Lam Q. Truong, The N. Nguyen, Hanh D. Vu, Hoa T. Nguyen, Lan T. Nguyen, Trang H. Pham, David Scott Mcvey, Hiep Vu

Nebraska Center for Virology: Faculty Publications

African swine fever virus (ASFV) is circulating in many swine-producing countries, causing significant economic losses. It is observed that pigs experimentally vaccinated with a live-attenuated virus (LAV) but not a killed virus (KV) vaccine develop solid homologous protective immunity. The objective of this study was to comparatively analyze antibody profiles between pigs vaccinated with an LAV vaccine and those vaccinated with a KV vaccine to identify potential markers of vaccineinduced protection. Thirty ASFV seronegative pigs were divided into three groups: Group 1 received a single dose of an experimental LAV, Group 2 received two doses of an experimental KV vaccine, …

Diaph1-Mfn2 Interaction Regulates Mitochondria-Sr/Er Contact And Modulates Ischemic/Hypoxic Stress, Gautham Yepuri, Lisa M Ramirez, Gregory G Theophall, Sergei V Reverdatto, Nosirudeen Quadri, Syed Nurul Hasan, Lei Bu, Devi Thiagarajan, Robin Wilson, Raquel López Díez, Paul F Gugger, Kaamashri Mangar, Navneet Narula, Stuart D Katz, Boyan Zhou, Huilin Li, Aleksandr B Stotland, Roberta A Gottlieb, Ann Marie Schmidt, Alexander Shekhtman, Ravichandran Ramasamy

Faculty, Staff and Student Publications

Inter-organelle contact and communication between mitochondria and sarco/endoplasmic reticulum (SR/ER) maintain cellular homeostasis and are profoundly disturbed during tissue ischemia. We tested the hypothesis that the formin Diaphanous-1 (DIAPH1), which regulates actin dynamics, signal transduction and metabolic functions, contributes to these processes. We demonstrate that DIAPH1 interacts directly with Mitofusin-2 (MFN2) to shorten mitochondria-SR/ER distance, thereby enhancing mitochondria-ER contact in cells including cardiomyocytes, endothelial cells and macrophages. Solution structure studies affirm the interaction between the Diaphanous Inhibitory Domain and the cytosolic GTPase domain of MFN2. In male rodent and human cardiomyocytes, DIAPH1-MFN2 interaction regulates mitochondrial turnover, mitophagy, and oxidative stress. …

Enolase Inhibitors As Early Lead Therapeutics Against Trypanosoma Brucei, Colm P Roster, Danielle Lavigne, Jillian E Milanes, Emily Knight, Heidi D Anderson, Sabrina Pizarro, Elijah M Harding, Meredith T Morris, Victoria C Yan, Cong-Dat Pham, Florian Muller, Samuel Kwain, Kerrick C Rees, Brian Dominy, Daniel C Whitehead, Md Nasir Uddin, Steven W Millward, James C Morris

Faculty, Staff and Student Publications

Glucose metabolism is critical for the African trypanosome, Trypanosoma brucei, serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against T. brucei ENO (TbENO) and found the compounds to be potent enzyme inhibitors and trypanocides. For example, (1-hydroxy-2-oxopyrrolidin-3-yl) phosphonic acid (deoxy-SF2312) …

Simian Immunodeficiency Virus-Infected Rhesus Macaques With Aids Co-Develop Cardiovascular Pathology And Encephalitis, Kevin S. White, Joshua A. Walker, John Wang, Patrick Autissier, Andrew D. Miller, Nadia N. Abuelezan, Rachel Burrack, Qingsheng Li, Woong-Ki Kim, Kenneth C. Williams

Nebraska Center for Virology: Faculty Publications

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/ macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently …

Co-Infection And Co-Localization Of Kaposi Sarcoma-Associated Herpesvirus And Epstein-Barr Virus In Hiv-Associated Kaposi Sarcoma: A Case Report, Peter Julius, Guobin Guobin, Stepfanie Siyumbwa, Jane Musumali, For Yue Tso, Owen Ngalamika, Trevor Kaile, Fred Maate, Phyllis Moonga, John T. West, Peter Angeletti, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi sarcoma (KS), a multifocal vascular neoplasm frequently observed in HIVpositive individuals, primarily affects the skin, mucous membranes, visceral organs, and lymph nodes. KS is associated primarily with Kaposi sarcomaassociated herpesvirus (KSHV) infection. In this case report, we present a rare occurrence of co-infection and co-localization of KSHV and Epstein-Barr virus (EBV) in KS arising from the conjunctiva, which, to our knowledge, has not been reported previously. Immunohistochemistry (IHC), DNA polymerase chain reaction (PCR), and EBV-encoded RNA in situ hybridization (EBER-ISH) were utilized to demonstrate the presence of KSHV and EBV infection in the ocular KS lesion. Nearly all KSHV-positive …

A Single-Dose Intramuscular Immunization Of Pigs With Lipid Nanoparticle Dna Vaccines Based On The Hemagglutinin Antigen Confers Complete Protection Against Challenge Infection With The Homologous Influenza Virus Strain, The N. Nguyen, Sushmita Kumari, Sarah Vitosh-Sillman, Jayeshbhai Chaudhari, Danh C. Lai, Hiep Vu

Nebraska Center for Virology: Faculty Publications

The Influenza A virus of swine (IAV-S) is highly prevalent and causes significant economic losses to swine producers. Due to the highly variable and rapidly evolving nature of the virus, it is critical to develop a safe and versatile vaccine platform that allows for frequent updates of the vaccine immunogens to cope with the emergence of new viral strains. The main objective of this study was to assess the feasibility of using lipid nanoparticles (LNPs) as nanocarriers for delivering DNA plasmid encoding the viral hemagglutinin (HA) gene in pigs. The intramuscular administration of a single dose of the LNP-DNA vaccines …

Using Noninvasive Calibrated Cuff Plethysmography To Observe The Effects Of Cold-Water Immersion On Arterial Compliance, Rita M. Grigorian

Master's Theses

As the prevalence of cardiovascular diseases continues to exponentially grow in populations across the globe, the necessity of determining underlying factors, effective methods of diagnoses, and universally available preventive measures also grows. Early detection of endothelial dysfunction, a proven precursor of cardiovascular diseases, can be extremely impactful in encouraging preventative measures and early intervention before medical conditions become chronic. In recent years, ice plunging, a form of cryotherapy involving full body immersion in cold water, has gained popularity within circles of fitness and health practitioners, gaining the interest of people of all backgrounds. Certain parallels observed between the human physiological …