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Full-Text Articles in Medical Immunology

Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood Jan 2015

Mcl1 Enhances The Survival Of Cd8+ Memory T Cells After Viral Infection, Jingang Gui, Zhuting Hu, Ching-Yi Tsai, Tian Ma, Yan Song, Amanda Morales, Li-Hao Huang, Ethan Dmitrovsky, Ruth Craig, Edward Usherwood

Dartmouth Scholarship

Viral infection results in the generation of massive numbers of activated effector CD8+ T cells that recognize viral components. Most of these are short-lived effector T cells (SLECs) that die after clearance of the virus. However, a small proportion of this population survives and forms antigen-specific memory precursor effector cells (MPECs), which ultimately develop into memory cells. These can participate in a recall response upon reexposure to antigen even at protracted times postinfection. Here, antiapoptotic myeloid cell leukemia 1 (MCL1) was found to prolong survival upon T cell stimulation, and mice expressing human MCL1 as a transgene exhibited a skewing …


Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson Jan 2015

Characterization Of Cd8+ T Cell Differentiation Following Sivδnef Vaccination By Transcription Factor Expression Profiling, James M. Billingsley, Premeela A. Rajakumar, Michelle A. Connole, Nadine C. Salisch, Sama Adnan, Yury V. Kuzmichev, Henoch S. Hong, R. Keith Reeves, Hyung-Joo Kang, Wenjun Li, Qingsheng Li, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

The onset of protective immunity against pathogenic SIV challenge in SIVΔnef-vaccinated macaques is delayed for 15-20 weeks, a process that is related to qualitative changes in CD8+ T cell responses induced by SIVΔnef. As a novel approach to characterize cell differentiation following vaccination, we used multi-target qPCR to measure transcription factor expression in naïve and memory subsets of CD8++ T cells, and in SIV-specific CD8+ T cells obtained from SIVΔnef-vaccinated or wild type SIVmac239-infected macaques. Unsupervised clustering of expression profiles organized naïve and memory CD8+ T cells into groups concordant with cell surface phenotype. Transcription factor …


Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang Jan 2015

Escherichia Coli Surface Display Of Single-Chain Antibody Vrc01 Against Hiv-1 Infection, Lin-Xu Wang, Michael Mellon, Dane Bowder, Meghan Quinn, Danielle Shea, Charles Wood, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from …


Evidence For Placental Hpv Infection In Both Hiv Positive And Negative Women, Chrispin Chisanga, Dawn Eggert, Charles D. Mitchell, Charles Wood, Peter C. Angeletti Jan 2015

Evidence For Placental Hpv Infection In Both Hiv Positive And Negative Women, Chrispin Chisanga, Dawn Eggert, Charles D. Mitchell, Charles Wood, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

Human papillomaviruses (HPVs) have previously been reported to infect epithelial trophoblast cells of the placenta. To investigate this possibility, 200 placental samples from Zambian women were separated into HIV+ and HIV− groups and tested for HPV by redundant primer PCR, using GP5+/GP6+ and CPI/CPII primer sets. Three HPV genotypes (HPV6, 16 and 90) were detected in placental samples. Whereas, 20 different HPV genotypes were detected in vaginal sampling of the same patients, suggesting that compartment specific sub-populations of HPV may exist. The incidence of HPV16 in placental samples was almost 2-fold greater in HIV+ women compared to HIV− (p = …


The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang Jan 2015

The Hippo/Yap Pathway Interacts With Egfr Signaling And Hpv Oncoproteins To Regulate Cervical Cancer Progression, Chunbo He, Dagan Mao, Guohua Hua, Xiangmin Lv, Xingcheng Chen, Peter C. Angeletti, Jixin Dong, Steven W. Remmenga, Kerry J. Rodabaugh, Jin Zhou, Paul F. Lambert, Peixin Yang, John S. Davis, Cheng Wang

Nebraska Center for Virology: Faculty Publications

The Hippo signaling pathway controls organ size and tumorigenesis

through a kinase cascade that inactivates Yes-associated

protein (YAP). Here, we show that YAP plays a central role in

controlling the progression of cervical cancer. Our results suggest

that YAP expression is associated with a poor prognosis for cervical

cancer. TGF-α and amphiregulin (AREG), via EGFR, inhibit the Hippo

signaling pathway and activate YAP to induce cervical cancer cell

proliferation and migration. Activated YAP allows for up-regulation

of TGF-α, AREG, and EGFR, forming a positive signaling loop to

drive cervical cancer cell proliferation. HPV E6 protein, a major

etiological molecule of …


Kaposi’S Sarcoma At The University Teaching Hospital, Lusaka, Zambia In The Antiretroviral Therapy Era, Owen Ngalamika, Veenu Minhas, Charles Wood Jan 2015

Kaposi’S Sarcoma At The University Teaching Hospital, Lusaka, Zambia In The Antiretroviral Therapy Era, Owen Ngalamika, Veenu Minhas, Charles Wood

Nebraska Center for Virology: Faculty Publications

With great interest, we read the recent publication “Kaposi’s sarcoma in HIV-infected patients in South Africa: Multicohort study in the antiretroviral therapy era” by Bohlius et al. We congratulate the authors for their contribution to this field. In this study the authors observed a decrease in incidence of Kaposi’s sarcoma (KS) in patients treated with anti-retroviral therapy (ART) when compared to patients who are not on ART. These results are encouraging because of the ongoing HIV epidemic in sub-Saharan Africa where KS is still one of the most prevalent cancers. Also, it is a relevant topic to study in …


Activation And Degradation Of Open Reading Frame 45 By The Replication And Transcription Activator Of Kaposi's Sarcoma-Associated Herpesvirus, Ying Wang, Kai Yu, Xiuzhi Pei, Tiancheng Zhang, Yuying Guo, Charles Wood, Jinzhong Wang Jan 2015

Activation And Degradation Of Open Reading Frame 45 By The Replication And Transcription Activator Of Kaposi's Sarcoma-Associated Herpesvirus, Ying Wang, Kai Yu, Xiuzhi Pei, Tiancheng Zhang, Yuying Guo, Charles Wood, Jinzhong Wang

Nebraska Center for Virology: Faculty Publications

The open reading frame 45 (ORF45) of the Kaposi's sarcoma-associated herpesvirus (KSHV) is an immediate-early phosphorylated tegument protein critical for viral escape from host immune surveillance. Its expression is upregulated by the viral replication and transcription activator (RTA), a key protein that controls the switch from latency to lytic replication. We report here that ORF45 expression was not only upregulated by RTA, but ORF45 could also be degraded by RTA in a proteasome-dependent manner. The ORF45 was activated by RTA via activation of the ORF45 promoter, and the promoter region from nt 69 271 to nt 69 026 was involved. …


Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown Jan 2015

Single-Dose Cpg Immunization Protects Against A Heterosubtypic Challenge And Generates Antigen-Specific Memory T Cells, Alexander J. Vogel, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Despite extensive research, influenza A virus (IAV) remains a major cause of morbidity, mortality, and healthcare expenditure. Emerging pandemics from highly pathogenic IAV strains, such as H5N1 and pandemic H1N1, highlight the need for universal, crossprotective vaccines. Current vaccine formulations generate strain-specific neutralizing antibodies primarily against the outer coat proteins, hemagglutinin and neuraminidase. In contrast to these highly mutable proteins, internal proteins of IAV are more conserved and are a favorable target for developing vaccines that induce strong T cell responses in addition to humoral immunity. Here, we found that intranasal administration with a single dose of CpG and inactivated …


Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache Jan 2015

Long-Acting Parenteral Combination Antiretroviral Loaded Nano-Drug Delivery System To Treat Chronic Hiv-1 Infection: A Humanized Mouse Model Study, Subhra Mandal, Guobin Kang, Pavan Kumar Prathipati, Wenjin Fan, Qingsheng Li, Christopher J. Destache

Nebraska Center for Virology: Faculty Publications

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir + tenofovir alafenamide + emtricitabine; EVG + TAF + FTC) drugs (mimicking marketed Genvoy® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored …


Acceptance And Uptake Of Influenza Vaccination By Health Care Workers, Leshonda Wallace Jan 2015

Acceptance And Uptake Of Influenza Vaccination By Health Care Workers, Leshonda Wallace

Walden Dissertations and Doctoral Studies

Influenza is a preventable infectious disease, against which vaccination is the primary means of protection. Health care workers (HCW) are among the most vulnerable to the illness and are likely to be sources of infection transmission while caring for patients. Circumstantial evidence suggests higher rates of vaccination coverage by HCW will coincide with a lower incidence of influenza transmission, yet a gap remains in the literature regarding governing health agencies' (i.e., licensing boards, medical and nursing associations) influence on the influenza vaccination practices of their constituents. Moreover, discrepancies exist between governing health agencies' and the National Vaccine Advisory Committee's recommendations …


Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan Dec 2014

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …


Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola Aug 2014

Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola

Dartmouth Scholarship

The worldwide administration of bivalent and quadrivalent HPV vaccines has resulted in cross-protection against non-vaccine HPV types. Infection with multiple HPV types may offer similar cross-protection in the natural setting. We hypothesized that infections with two or more HPV types from the same species, and independently, infections with two or more HPV types from different species, associate with protection from high-grade lesions.


Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver Aug 2014

Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and …


The Mucosal Expression Pattern Of Interferon-Ε In Rhesus Macaques, Andrew Demers, Guobin Kang, Fangrui Ma, Wuxun Lu, Zhe Yuan, Yue Li, Mark Lewis, Edmundo N. Kraiselburd, Luis Montaner, Qingsheng Li Aug 2014

The Mucosal Expression Pattern Of Interferon-Ε In Rhesus Macaques, Andrew Demers, Guobin Kang, Fangrui Ma, Wuxun Lu, Zhe Yuan, Yue Li, Mark Lewis, Edmundo N. Kraiselburd, Luis Montaner, Qingsheng Li

Qingsheng Li Publications

Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the …


Crohn’S Disease Linked Polymorphisms Associated With Autophagy Contribute To Th17 Cell Induction Through Increasing The Expression Of Il-1Β And Tnf-Α, Daniel Clayton Morse Jun 2014

Crohn’S Disease Linked Polymorphisms Associated With Autophagy Contribute To Th17 Cell Induction Through Increasing The Expression Of Il-1Β And Tnf-Α, Daniel Clayton Morse

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Genome wide association studies (GWAS) have linked polymorphisms in autophagy genes to Crohn’s Disease (CD). Interestingly, recent studies have shown that defective autophagy leads to increased levels of the cytokines IL-1b and TNF-a, which play a critical role in Th17 cell differentiation. This is significant because CD is marked by a Th17 cell mediated inflammatory response. This article examines the manners in which defective expression of autophagy linked proteins, can indirectly amplify and sustain Th17 cell induction through increasing the production of Th17 positively differentiating cytokines (IL-1b and TNF-a) and decreasing the production of a Th17 down regulating cytokine, IL-10.


Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder Jun 2014

Immunomodulatory Activity Of Interferon-Beta, Lloyd H. Kasper, Anthony T. Reder

Dartmouth Scholarship

Multiple sclerosis (MS) is a complex disorder of the central nervous system that appears to be driven by a shift in immune functioning toward excess inflammation that results in demyelination and axonal loss. Beta interferons were the first class of disease-modifying therapies to be approved for patients with MS after treatment with this type I interferon improved the course of MS on both clinical and radiological measures in clinical trials. The mechanism of action of interferon-beta appears to be driven by influencing the immune system at many levels, including antigen-presenting cells, T cells, and B cells. One effect of these …


Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer May 2014

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …


Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer May 2014

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …


Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap Apr 2014

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …


Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Michael A. Barry, Eric A. Weaver Mar 2014

Cd46-Mediated Transduction Of A Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy, Zenaido T. Camacho, Michael A. Barry, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The …


Autoantibodies To Agrin In Myasthenia Gravis Patients, Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wen-Cheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei Mar 2014

Autoantibodies To Agrin In Myasthenia Gravis Patients, Bin Zhang, Chengyong Shen, Beverly Bealmear, Samia Ragheb, Wen-Cheng Xiong, Richard A. Lewis, Robert P. Lisak, Lin Mei

Immunology and Microbiology Faculty Research Publications

To determine if patients with myasthenia gravis (MG) have antibodies to agrin, a proteoglycan released by motor neurons and is critical for neuromuscular junction (NMJ) formation, we collected serum samples from 93 patients with MG with known status of antibodies to acetylcholine receptor (AChR), muscle specific kinase (MuSK) and lipoprotein-related 4 (LRP4) and samples from control subjects (healthy individuals and individuals with other diseases). Sera were assayed for antibodies to agrin. We found antibodies to agrin in 7 serum samples of MG patients. None of the 25 healthy controls and none of the 55 control neurological patients had agrin antibodies. …


Deep Rna Sequencing Reveals Hidden Features And Dynamics Of Early Gene Transcription In Paramecium Bursaria Chlorella Virus 1, Guillaume Blanc, Michael Mozar, Irina V. Agarkova, James R. Gurnon, Giane Yanai-Balser, Janet M. Rowe, Yuannan Xia, Jean-Jack Riethoven, David D. Dunigan, James L. Van Etten Mar 2014

Deep Rna Sequencing Reveals Hidden Features And Dynamics Of Early Gene Transcription In Paramecium Bursaria Chlorella Virus 1, Guillaume Blanc, Michael Mozar, Irina V. Agarkova, James R. Gurnon, Giane Yanai-Balser, Janet M. Rowe, Yuannan Xia, Jean-Jack Riethoven, David D. Dunigan, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of the genus Chlorovirus (family Phycodnaviridae) that infects the unicellular, eukaryotic green alga Chlorella variabilis NC64A. The 331-kb PBCV-1 genome contains 416 major open reading frames. A mRNA-seq approach was used to analyze PBCV-1 transcriptomes at 6 progressive times during the first hour of infection. The alignment of 17 million reads to the PBCV-1 genome allowed the construction of single-base transcriptome maps. Significant transcription was detected for a subset of 50 viral genes as soon as 7 min after infection. By 20 min post infection (p.i.), transcripts were detected for …


Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver Mar 2014

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus Types 4 and 7 (Ad4 and Ad7) are associated with acute respiratory distress (ARD). In order to prevent widespread Ad-associated ARD (Ad-ARD) the United States military immunizes new recruits using a safe and effective lyophilized wildtype Ad4 and Ad7 delivered orally in an enteric-coated capsule. We cloned Ad4 and Ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (HA1-con). BALB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). Ad4 induced significantly higher luciferase expression levels as compared with Ad7 by both routes. Ad7 transduction was restored …


Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin Feb 2014

Systematic Analysis Of A Xenograft Mice Model For Kshv+ Primary Effusion Lymphoma (Pel), Lu Dai, Jimena Trillo-Tinoco, Lihua Bai, Baoli Kang, Zengguang Xu, Xiaofei Wen, Luis Del Valle, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi's sarcoma-associated herpesvirus is the causative agent of primary effusion lymphoma (PEL), which arises preferentially in the setting of infection with human immunodeficiency virus (HIV). Even with standard cytotoxic chemotherapy, PEL continues to cause high mortality rates, requiring the development of novel therapeutic strategies. PEL xenograft models employing immunodeficient mice have been used to study the in vivo effects of a variety of therapeutic approaches. However, it remains unclear whether these xenograft models entirely reflect clinical presentations of KSHV(+) PEL, especially given the recent description of extracavitary solid tumor variants arising in patients. In addition, effusion and solid tumor cells …


Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang Feb 2014

Anakinra And Related Drugs Targeting Interleukin-1 In The Treatment Of Cryopyrin-Associated Periodic Syndromes, Inessa Bachove, Christopher Chang

Department of Pediatrics Faculty Papers

Anakinra is an interleukin (IL) receptor antagonist that works by blocking the biological activity of IL-1 by competitively inhibiting binding of IL-1 to the type 1 interleukin receptor. IL-1 production is induced in response to inflammatory stimuli and mediates various physiological mechanisms, including inflammation and immunological reactions. Patients with neonatal onset multisystem inflammatory disease (NOMID) produce excess IL-1β, a major proinflammatory cytokine that regulates innate immune responses. Anakinra binds competitively and this results in a rapid reduction in disease severity. NOMID, also known as chronic infantile neurologic, cutaneous, articular syndrome, is the most severe clinical phenotype in the spectrum of …


A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan Feb 2014

A Melanin-Independent Interaction Between Mc1r And Met Signalling Pathways Is Required For Hgf-Dependent Melanoma, Agnieszka Wolnicka-Głubisz, Faith M. Strickland, Albert Wielgus, Miriam Anver, Glenn Merlino, Edward C. De Fabo, Frances P. Noonan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Melanocortin 1 receptor (MC1R) signaling stimulates black eumelanin production through a cAMP-dependent pathway. MC1R polymorphisms can impair this process, resulting in a predominance of red phaeomelanin. The red hair, fair skin and UV sensitive phenotype is a well-described melanoma risk factor. MC1R polymorphisms also confer melanoma risk independent of pigment. We investigated the effect of Mc1r deficiency in a mouse model of UV-induced melanoma. C57BL/6-Mc1r+/+-HGF transgenic mice have a characteristic hyperpigmented black phenotype with extra-follicular dermal melanocytes located at the dermal/epidermal junction. UVB induces melanoma, independent of melanin pigmentation, but UVA-induced and spontaneous melanomas are dependent on black eumelanin. We …


Inflammation Enhances Il-2 Driven Differentiation Of Cytolytic Cd4 T Cells, Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M. Brown Feb 2014

Inflammation Enhances Il-2 Driven Differentiation Of Cytolytic Cd4 T Cells, Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing …


Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois Feb 2014

Candida Albicans Als5p Amyloid In Host-Microbe Interactions: A Ceanorhabditis Elegans Study, Michael Bois

Dissertations, Theses, and Capstone Projects

Candida albicans, a dimorphic fungus and an opportunistic pathogen, possesses a myriad of adherence factors including members of the agglutinin-like sequence (Als) family of mannoproteins. The adhesin Als5p mediates adhesion to many substrates, and is upregulated during commensal interactions, but is downregulated during active C. albicans infections[1]. An amyloid forming core sequence at residues 325-331 has been shown to be important for Als5p function, because a single amino acid substitution at position 326 (V326N) greatly reduces Als5p-mediated adherence[2]. We evaluated the role of Als5p in host-microbe interactions, using Caenorhabditis elegans as a host model and feeding them Saccharomyces cerevisiae expressing …


An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski Feb 2014

An Ethnobotanical, Ecological And Lc-Ms-Based Chemometric Investigation Of Phaleria Nisidai, A Traditional Adaptogen Containing Diterpene Esters From Palau, Micronesia, Daniel Kulakowski

Dissertations, Theses, and Capstone Projects

An ethnobotanical, ecological and LC-MS-based chemometric investigation of Phaleria nisidai, a traditional adaptogen containing diterpene esters from Palau, Micronesia

Palau is a country with a rich heritage of traditional medicine still being practiced. One of the most popular and respected remedies in Palau is a tea made from fresh leaves of Phaleria nisidai Kaneh. (Thymelaeaceae). Interviews conducted to determine the use of this plant revealed that it is employed non-specifically to treat a variety of general health concerns. Its use as a prophylactic to keep away sickness, as a 'system cleaner', as well as for strength and energy indicate …


Quantitative Evaluation Of Microglial Activation And Vascularization In Suicide, Tatiana Pavlovna Schnieder Feb 2014

Quantitative Evaluation Of Microglial Activation And Vascularization In Suicide, Tatiana Pavlovna Schnieder

Dissertations, Theses, and Capstone Projects

Accumulated evidence points to immunological factors in psychiatric disorders. In a variety of chronic neurological disorders, exacerbation is associated with inflammation and a loss of integrity of the blood-brain barrier. Microglia, the principal brain immunological cells in the healthy state, respond to changes in the internal environment of the brain through a sequence of activated states. This study compared microglial phenotypes in the white matter of autopsy brains from 11 suicide victims and 25 subjects who died involuntarily. Both groups included cases with and without major psychiatric disorders, which were determined by PA interviews. Cases were matched for sex, age, …