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Medical Immunology Commons

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Articles 451 - 480 of 2005

Full-Text Articles in Medical Immunology

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan Jan 2023

Chromosomal Microarray Analysis Supplements Exome Sequencing To Diagnose Children With Suspected Inborn Errors Of Immunity, Breanna J Beers, Morgan N Similuk, Rajarshi Ghosh, Bryce A Seifert, Leila Jamal, Michael Kamen, Michael R Setzer, Colleen Jodarski, Rylee Duncan, Devin Hunt, Madison Mixer, Wenjia Cao, Weimin Bi, Daniel Veltri, Eric Karlins, Lingwen Zhang, Zhiwen Li, Andrew J Oler, Kathleen Jevtich, Yunting Yu, Haley Hullfish, Bibiana Bielekova, Pamela Frischmeyer-Guerrerio, An Dang Do, Laryssa A Huryn, Kenneth N Olivier, Helen C Su, Jonathan J Lyons, Christa S Zerbe, V Koneti Rao, Michael D Keller, Alexandra F Freeman, Steven M Holland, Luis M Franco, Magdalena A Walkiewicz, Jia Yan

Faculty, Staff and Students Publications

PURPOSE: Though copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.

METHODS: We performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.

RESULTS: Of the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by …


Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan Jan 2023

Growth And Differentiation Factor 15 (Gdf15) Levels Predict Adverse Respiratory Outcomes In Premature Neonates, Faeq Almudares, Joseph Hagan, Xinpu Chen, Sridevi Devaraj, Bhagavatula Moorthy, Krithika Lingappan

Faculty, Staff and Students Publications

Growth and differentiation factor 15 (GDF15) is a stress-responsive cytokine, and its expression increases during inflammation, hyperoxia, and senescence. Significantly, GDF15 is secreted by the placenta, and maternal levels increase throughout pregnancy. Serum GDF15 level is a promising biomarker for many lung diseases like pulmonary hypertension and pulmonary fibrosis. However, circulating GDF15 levels in preterm infants and their role as a predictor of respiratory outcomes have not been studied. We hypothesized that GDF15 levels would increase with gestational age at birth, and that postnatal GDF15 will be correlated with adverse respiratory outcomes in preterm infants. Scavenged blood samples were retrieved …


Resident Education And Virtual Medicine: A Faculty Development Session To Enhance Trainee Skills In The Realm Of Telemedicine, Anna E Rueda, Ana C Monterrey, Margaret Wood, Linessa Zuniga, Betty Del Rio Rodriguez Jan 2023

Resident Education And Virtual Medicine: A Faculty Development Session To Enhance Trainee Skills In The Realm Of Telemedicine, Anna E Rueda, Ana C Monterrey, Margaret Wood, Linessa Zuniga, Betty Del Rio Rodriguez

Faculty, Staff and Students Publications

INTRODUCTION: COVID-19 accelerated the use of telemedicine. Subsequently, clinical sites began conducting virtual visits. Academic institutions implemented telemedicine for patient care and simultaneously had to teach residents the logistics and best practices. To meet this need, we developed a training session for faculty focused on telemedicine best practices and teaching telemedicine in the pediatric realm.

METHODS: We designed this training session based on institutional and society guidelines and faculty experience with telemedicine. Objectives included telemedicine documentation, triage, counseling, and ethical issues in telemedicine. We conducted all sessions in a 60-minute or 90-minute format over a virtual platform for small and …


Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand Jan 2023

Alveolar Macrophages In Lung Cancer: Opportunities Challenges, Cheng-Yen Chang, Dominique Armstrong, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

Alveolar macrophages (AMs) are critical components of the innate defense mechanism in the lung. Nestled tightly within the alveoli, AMs, derived from the yolk-sac or bone marrow, can phagocytose foreign particles, defend the host against pathogens, recycle surfactant, and promptly respond to inhaled noxious stimuli. The behavior of AMs is tightly dependent on the environmental cues whereby infection, chronic inflammation, and associated metabolic changes can repolarize their effector functions in the lungs. Several factors within the tumor microenvironment can re-educate AMs, resulting in tumor growth, and reducing immune checkpoint inhibitors (ICIs) efficacy in patients treated for non-small cell lung cancer …


Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar Jan 2023

Covid-19 And Pregnancy: Clinical Outcomes; Mechanisms, And Vaccine Efficacy, Deepak Kumar, Sonam Verma, Indira U Mysorekar

Faculty, Staff and Students Publications

As the COVID-19 pandemic continues into its third year, emerging data indicates increased risks associated with SARS-CoV-2 infection during pregnancy, including pre-eclampsia, intrauterine growth restriction, preterm birth, stillbirth, and risk of developmental defects in neonates. Here, we review clinical reports to date that address different COVID-19 pregnancy complications. We also document placental pathologies induced by SARS-CoV-2 infection, entry mechanisms in placental cells, and immune responses at the maternal-fetal interface. Since new variants of SARS-CoV-2 are emerging with characteristics of higher transmissibility and more effective immune escape strategies, we also briefly highlight the genomic and proteomic features of SARS-CoV-2 investigated to …


Targeting Hiv-1 Reservoirs In T Cell Subsets, Min Li, Marietta M Budai, Min Chen, Jin Wang Jan 2023

Targeting Hiv-1 Reservoirs In T Cell Subsets, Min Li, Marietta M Budai, Min Chen, Jin Wang

Faculty, Staff and Students Publications

The HIV-1 reservoirs harbor the latent proviruses that are integrated into the host genome. It is a challenging task to eradicate the proviruses in order to achieve an HIV cure. We have described a strategy for the clearance of HIV-1 infection through selective elimination of host cells harboring replication-competent HIV (SECH), by inhibition of autophagy and promotion of apoptosis during viral re-activation. HIV-1 can infect various CD4+ T cell subsets, but it is not known whether the SECH approach is equally effective in targeting HIV-1 reservoirs in these different subsets in vivo. In a humanized mouse model, we found …


Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man Jan 2023

Lox Upregulates Fak Phosphorylation To Promote Metastasis In Osteosarcoma, Xiang Chen, Margaret Clement, M John Hicks, Poonam Sarkar, M Waleed Gaber, Tsz-Kwong Man

Faculty, Staff and Students Publications

Osteosarcoma is a malignant bone tumor that commonly occurs in the pediatric population. Despite the use of chemotherapy and surgery, metastasis remains to be the leading cause of death in patients with osteosarcoma. We have previously reported that cytoplasmic mislocalization of p27 is associated with a poor outcome in osteosarcoma. In this study, we further show that lysyl oxidase (LOX) expression was associated with p27 mislocalization. LOX is an enigmatic molecule that acts as a tumor suppressor or a metastatic promoter; however, its role in osteosarcoma is still unclear. Hence, we performed both


Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar Jan 2023

Effects Of Aging On Urinary Tract Epithelial Homeostasis And Immunity, Marianne M Ligon, Chetanchandra S Joshi, Bisiayo E Fashemi, Arnold M Salazar, Indira U Mysorekar

Faculty, Staff and Students Publications

A global increase in older individuals creates an increasing demand to understand numerous healthcare challenges related to aging. This population is subject to changes in tissue physiology and the immune response network. Older individuals are particularly susceptible to infectious diseases, with one of the most common being urinary tract infections (UTIs). Postmenopausal and older women have the highest risk of recurrent UTIs (rUTIs); however, why rUTIs become more frequent after menopause and during old age is incompletely understood. This increased susceptibility and severity among older individuals may involve functional changes to the immune system with age. Aging also has substantial …


Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman Jan 2023

Engaging Patients In Antimicrobial Stewardship: Co-Designed Educational Tool To Improve Periprocedural Care Through De-Implementation Of Guideline-Discordant Antimicrobial Use, Hawra Al Lawati, Marlena Shin, Rebecca Lamkin, Tyler Thompson, Isabella Epshtein, Hillary Mull, Dipandita Basnet Thapa, Dimitri Drekonja, Maria C Rodriguez-Barradas, Teena Huan Xu, Howard Gold, A Rani Elwy, Judy Strymish, Westyn Branch-Elliman

Faculty, Staff and Students Publications

Effective de-implementation models often include replacement of an ineffective practice with an alternative. We co-developed patient education materials as a replacement strategy for inappropriate post-procedural antibiotics in cardiac device procedures. Lessons learned and developed materials may be used to promote infection prevention in other periprocedural settings.


Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations Jan 2023

Combining Charlson Comorbidity And Vacs Indices Improves Prognostic Accuracy For All-Cause Mortality For Patients With And Without Hiv In The Veterans Health Administration, Kathleen A Mcginnis, Amy C Justice, Vincent C Marconi, Maria C Rodriguez-Barradas, Ronald G Hauser, Krisann K Oursler, Sheldon T Brown, Kendall J Bryant, Janet P Tate, Veterans Aging Cohort Study Affiliations

Faculty, Staff and Students Publications

INTRODUCTION: As people age with HIV (PWH), many comorbid diseases are more common than among age matched comparators without HIV (PWoH). While the Veterans Aging Cohort (VACS) Index 2.0 accurately predicts mortality in PWH using age and clinical biomarkers, the only included comorbidity is hepatitis C. We asked whether adding comorbid disease groupings from the Charlson Comorbidity Index (CCI) improves the accuracy of VACS Index.

METHODS: To maximize our ability to model mortality among older age groups, we began with PWoH in Veterans Health Administration (VA) from 2007-2017, divided into development and validation samples. Baseline predictors included age, and components …


Hypoxia Regulates Vessel-Modifying Macrophages And Vice Versa In Tumors, Kayla Jo Steinberger Jan 2023

Hypoxia Regulates Vessel-Modifying Macrophages And Vice Versa In Tumors, Kayla Jo Steinberger

Graduate Theses, Dissertations, and Problem Reports (ETD)

Hypoxia, or low oxygen, is a common feature of solid tumors correlating with poor survival in cancer patients. Growing tumors need a blood supply to deliver oxygen. Tumors attempt to re-acquire oxygen by forming new blood vessels from nearby, pre-existing vessels, a process known as angiogenesis. Past treatments aimed at preventing this process yielded not only disappointing results in the clinic but sometimes worsened the patient’s prognosis making the tumor more hypoxic, emphasizing the urgent need for novel targets. In tumors, angiogenesis is notoriously dysfunctional resulting in leaky, under-perfused blood vessels which cannot adequately deliver oxygen and exacerbates hypoxia. Emerging …


Development And Characterization Of Monoclonal Antibodies Against Pseudomonas Aeruginosa, Jason Kang Jan 2023

Development And Characterization Of Monoclonal Antibodies Against Pseudomonas Aeruginosa, Jason Kang

Graduate Theses, Dissertations, and Problem Reports (ETD)

Antimicrobial resistance (AMR) has emerged as a global crisis, posing significant challenges to the treatment and management of infectious diseases. The escalating prevalence of antibiotic-resistant bacteria has made many antimicrobial therapies ineffective, necessitating the development of alternative strategies to combat microbial infections. The rise of multidrug-resistant pathogens, such as Pseudomonas aeruginosa and Serratia marcescens, further exacerbates this problem, as these pathogens exhibit high levels of resistance to multiple antibiotics and cause severe infections in vulnerable populations. In response to the need for alternative therapeutic approaches, monoclonal antibodies (mAbs) have emerged as promising candidates for combating AMR. In this work, we …


C4b-Binding Protein Inhibits Particulate- And Crystalline-Induced Nlrp3 Inflammasome Activation, Damien Bierschenk, Nikolina Papac-Milicevic, Ian P Bresch, Valentina Kovacic, Serena Bettoni, Mateusz Dziedzic, Rick A Wetsel, Susanne Eschenburg, Christoph J Binder, Anna M Blom, Ben C King Jan 2023

C4b-Binding Protein Inhibits Particulate- And Crystalline-Induced Nlrp3 Inflammasome Activation, Damien Bierschenk, Nikolina Papac-Milicevic, Ian P Bresch, Valentina Kovacic, Serena Bettoni, Mateusz Dziedzic, Rick A Wetsel, Susanne Eschenburg, Christoph J Binder, Anna M Blom, Ben C King

Faculty, Staff and Student Publications

Dysregulated NLRP3 inflammasome activation drives a wide variety of diseases, while endogenous inhibition of this pathway is poorly characterised. The serum protein C4b-binding protein (C4BP) is a well-established inhibitor of complement with emerging functions as an endogenously expressed inhibitor of the NLRP3 inflammasome signalling pathway. Here, we identified that C4BP purified from human plasma is an inhibitor of crystalline- (monosodium urate, MSU) and particulate-induced (silica) NLRP3 inflammasome activation. Using a C4BP mutant panel, we identified that C4BP bound these particles


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 Jan 2023

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.


Spatial Heterogeneity Of T Cell Repertoire Across Nsclc Tumors, Tumor Edges, Adjacent And Distant Lung Tissues, Qikang Hu, Meredith L Frank, Yang Gao, Liyan Ji, Muyun Peng, Chen Chen, Bin Wang, Yan Hu, Zeyu Wu, Jina Li, Lu Shu, Qiongzhi He, Yingqian Zhang, Xuefeng Xia, Jianjun Zhang, Xin Yi, Alexandre Reuben, Fenglei Yu Jan 2023

Spatial Heterogeneity Of T Cell Repertoire Across Nsclc Tumors, Tumor Edges, Adjacent And Distant Lung Tissues, Qikang Hu, Meredith L Frank, Yang Gao, Liyan Ji, Muyun Peng, Chen Chen, Bin Wang, Yan Hu, Zeyu Wu, Jina Li, Lu Shu, Qiongzhi He, Yingqian Zhang, Xuefeng Xia, Jianjun Zhang, Xin Yi, Alexandre Reuben, Fenglei Yu

Faculty, Staff and Student Publications

BACKGROUND: A better understanding of T cells in lung cancer and their distribution across tumor-adjacent lungs and peripheral blood is needed to improve efficacy and minimize toxicity from immunotherapy to lung cancer patients.

METHODS: Here, we performed CDR3β TCR sequencing of 136 samples from 20 patients with early-stage NSCLC including peripheral blood mononuclear cells, tumors, tumor edges (tumor), as well as adjacent lungs 1 cm, 2 cm, 5 cm, and 10 cm away from the tumor to gain insight into the spatial heterogeneity of T cells across the lungs in patients with NSCLC. PD-L1, CD4, and CD8 expression was assessed …


Next-Generation Ctla-4 Targeting Molecules And Combination Therapy: Promising Strategies For Improving Cancer Immunotherapy, Nils-Petter Rudqvist, Manushak Avagyan, Dhan Chand Jan 2023

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.


A Bibliometric And Visual Analysis Of Cancer-Associated Fibroblasts, Wei-Chen Yuan, Jie-Xiang Zhang, Hai-Bin Chen, Ying Yuan, Yu-Pei Zhuang, Hong-Li Zhou, Mu-Han Li, Wen-Li Qiu, Hong-Guang Zhou Jan 2023

A Bibliometric And Visual Analysis Of Cancer-Associated Fibroblasts, Wei-Chen Yuan, Jie-Xiang Zhang, Hai-Bin Chen, Ying Yuan, Yu-Pei Zhuang, Hong-Li Zhou, Mu-Han Li, Wen-Li Qiu, Hong-Guang Zhou

Faculty, Staff and Student Publications

Background: Cancer-associated fibroblasts (CAFs) represent the predominant stromal component within the tumour microenvironment (TME), exhibiting considerable heterogeneity and plasticity that significantly impact immune response and metabolic reprogramming within the TME, thereby influencing tumour progression. Consequently, investigating CAFs is of utmost importance. The objective of this study is to employ bibliometric analysis in order to evaluate the current state of research on CAFs and predict future areas of research and emerging trends.

Methods: Conduct a comprehensive search for scholarly publications within the Web of Science Core Collection database, encompassing the time period from January 1, 2001, to December 31, 2022. Apply …


Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro Jan 2023

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Antônio L Teixeira, Fabiola M Ribeiro

Faculty, Staff and Student Publications

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …


Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons Jan 2023

Targeting Immunosuppressive Ly6c+ Classical Monocytes Reverses Anti-Pd-1/Ctla-4 Immunotherapy Resistance, B Leticia Rodriguez, Limo Chen, Yanli Li, Shucheng Miao, David H Peng, Jared J Fradette, Lixia Diao, Jessica M Konen, Frank R Rojas Alvarez, Luisa M Solis, Xiaohui Yi, Aparna Padhye, Laura A Gibson, Joshua K Ochieng, Xiaofei Zhou, Jing Wang, Don L Gibbons

Faculty, Staff and Student Publications

Introduction: Despite significant clinical advancement with the use of immune checkpoint blockade (ICB) in non-small cell lung cancer (NSCLC) there are still a major subset of patients that develop adaptive/acquired resistance. Understanding resistance mechanisms to ICB is critical to developing new therapeutic strategies and improving patient survival. The dynamic nature of the tumor microenvironment and the mutational load driving tumor immunogenicity limit the efficacy to ICB. Recent studies indicate that myeloid cells are drivers of ICB resistance. In this study we sought to understand which immune cells were contributing to resistance and if we could modify them in a way …


Cancer-Associated Pyroptosis: A New License To Kill Tumor, Qing Kong, Zhibin Zhang Jan 2023

Cancer-Associated Pyroptosis: A New License To Kill Tumor, Qing Kong, Zhibin Zhang

Faculty, Staff and Student Publications

Pyroptosis is a programmed necrotic cell death mediated by pore-forming Gasdermin (GSDM) proteins. After being unleashed from the C-terminal auto-inhibitory domains by proteolytic cleavage, the N-terminal domains of GSDMs oligomerize and perforate on the plasma membrane to induce cytolytic pyroptosis, releasing immune mediators and alarming the immune system. Upon infection or danger signal perception, GSDMD that functions downstream of the inflammasome, a supramolecular complex for inflammatory caspase activation, is cleaved and activated by inflammasome-activated caspase-1/4/5/11 in immune cells and epithelial cells to trigger pyroptosis and exert anti-infection protection. Unlike this inflammasome-activated pyroptosis (IAP), recent studies also suggest an emerging role …


Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino Dec 2022

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …


Loss Of Ubiquitin-Specific Peptidase 18 Destabilizes 14-3-3Ζ Protein And Represses Lung Cancer Metastasis, Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V Ferry-Galow, Ralph E Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M Kurie, Jaime Rodriguez-Canales, Xi Liu, Ethan Dmitrovsky Dec 2022

Loss Of Ubiquitin-Specific Peptidase 18 Destabilizes 14-3-3Ζ Protein And Represses Lung Cancer Metastasis, Zibo Chen, Lin Zheng, Yulong Chen, Xiuxia Liu, Masanori Kawakami, Lisa Maria Mustachio, Jason Roszik, Katherine V Ferry-Galow, Ralph E Parchment, Xin Liu, Thorkell Andresson, Gerard Duncan, Jonathan M Kurie, Jaime Rodriguez-Canales, Xi Liu, Ethan Dmitrovsky

Faculty, Staff and Student Publications

Cancer metastasis is a major cause of cancer-related mortality. Strategies to reduce metastases are needed especially in lung cancer, the most common cause of cancer mortality. We previously reported increased ubiquitin-specific peptidase 18 (USP18) expression in lung and other cancers. Engineered reduction of USP18 expression repressed lung cancer growth and promoted apoptosis. This deubiquitinase (DUB) stabilized targeted proteins by removing the complex interferon-stimulated gene 15 (ISG15). This study explores if the loss of USP18 reduced lung cancer metastasis. USP18 knock-down in lung cancer cells was independently achieved using small hairpin RNAs (shRNAs) and small interfering RNAs (siRNAs). USP18 knock-down reduced …


A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy Dec 2022

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy

Nebraska Center for Virology: Faculty Publications

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in …


Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura Dec 2022

Role Of Adenylyl Cyclase Type 7 In Functions Of Bv-2 Microglia, Yawen Hu, Rebecca A. Hill, Masami Yoshimura

School of Medicine Faculty Publications

To assess the role of adenylyl cyclase type 7 (AC7) in microglia’s immune function, we generated AC7 gene knockout (AC7 KO) clones from a mouse microglial cell line, BV-2, using the CRISPR-Cas9 gene editing system. The ability of BV-2 cells to generate cAMP and their innate immune functions were examined in the presence or absence of ethanol. The parental BV-2 cells showed robust cAMP production when stimulated with prostaglandin-E1 (PGE1) and ethanol increased cAMP production in a dose-dependent manner. AC7 KO clones of BV-2 cells showed diminished and ethanol-insensitive cAMP production. The phagocytic activity of the parental BV-2 cells was …


Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa Dec 2022

Proximity-Dependent Biotin Labeling In Testicular Germ Cells Identified Tesmin-Associated Proteins, Seiya Oura, Akinori Ninomiya, Fuminori Sugihara, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

Characterization of protein-protein interactions (PPI) is a key to understanding the functions of proteins of interest. Recently developed proximity-dependent biotin identification (BioID) has been actively investigated as an alternative PPI mapping method because of its usefulness in uncovering transient PPI. Here, as an example of proximity labeling proteomics application in the testis, we generated two transgenic mouse lines expressing two biotin ligases (BioID2 or TurboID) fused with TESMIN, which translocates from the cytosol to the nucleus during meiotic progression and is required for reproduction. The BioID2 transgene, albeit not the TurboID transgene, rescued fertility defects of the Tesmin KO male …


Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies, Mukul Singal, Sanjana Kalvehalli Kashinath, S. Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed Dec 2022

Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies, Mukul Singal, Sanjana Kalvehalli Kashinath, S. Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed

Advances in Clinical Medical Research and Healthcare Delivery

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies.

We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies.

A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive …


Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder Dec 2022

Surveillance Of Antimicrobial Resistance In Veterinary Medicine In The United States: Current E, Juliana M. Ruzante, Beth Harris, Paul Plummer, Raissa R. Raineri, John Dustin Loy, Megan Jacob, Orhan Sahin, Amanda J. Kreuder

Nebraska Center for Virology: Faculty Publications

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts to reduce the potential for emergence …


The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen Dec 2022

The Role Of Lncrnas In The Tumor Microenvironment And Immunotherapy Of Melanoma, Wencheng Zhou, Xuewen Xu, Ying Cen, Junjie Chen

Faculty, Staff and Student Publications

Melanoma is one of the most lethal tumors with highly aggressive and metastatic properties. Although immunotherapy and targeted therapy have certain therapeutic effects in melanoma, a significant proportion of patients still have drug resistance after treatment. Recent studies have shown that long noncoding RNAs (lncRNAs) are widely recognized as regulatory factors in cancer. They can regulate numerous cellular processes, including cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) progression and the immune microenvironment. The role of lncRNAs in malignant tumors has received much attention, whereas the relationship between lncRNAs and melanoma requires further investigation. Our review summarizes tumor suppressive and oncogenic lncRNAs …


Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon Dec 2022

Single Cell Rna Sequencing Of The Adult Drosophila Eye Reveals Distinct Clusters And Novel Marker Genes For All Major Cell Types, Kelvin Yeung, Komal Kumar Bollepogu Raja, Yoon-Kyung Shim, Yumei Li, Rui Chen, Graeme Mardon

Faculty, Staff and Students Publications

The adult Drosophila eye is a powerful model system for phototransduction and neurodegeneration research. However, single cell resolution transcriptomic data are lacking for this tissue. We present single cell RNA-seq data on 1-day male and female, 3-day and 7-day old male adult eyes, covering early to mature adult eyes. All major cell types, including photoreceptors, cone and pigment cells in the adult eye were captured and identified. Our data sets identified novel cell type specific marker genes, some of which were validated in vivo. R7 and R8 photoreceptors form clusters that reflect their specific Rhodopsin expression and the specific Rhodopsin …


Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille Dec 2022

Genotype Classification Of Moraxella Bovis Using Maldi-Tof Ms Profiles, Hannah G. Olson, John Dustin Loy, Michael L. Clawson, Emily L. Wynn, Matthew M. Hille

Nebraska Center for Virology: Faculty Publications

Moraxella bovis (M. bovis) is regarded as a causative agent of infectious bovine keratoconjunctivitis (IBK), the most common ocular disease of cattle. Recently, whole genome sequencing identified the presence of two distinct genotypes within M. bovis that differ in chromosome content, potential virulence factors, as well as prophage and plasmid profiles. It is unclear if the genotypes equally associate with IBK or if one is more likely to be isolated from IBK lesions. We utilized 39 strains of M. bovis that had previously undergone whole genome sequencing and genotype classification to determine the utility of matrix-assisted laser desorption/ionization …