Digital Commons Network^™

Activation Of Multiple Apoptotic Pathways In Human Nasopharyngeal Carcinoma Cells By The Prenylated Isoflavone, Osajin, Tsung-Teng Huang, Fu-Guo Liu, Chia-Fong Wei, Chia-Chen Lu, Chang-Chieh Chen, Hung-Chi Lin, David M. Ojcius, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC) cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL), suppression of glucose-regulated protein 78 kDa (GRP78), and activation of caspases-9, -8, …

Epignetics And Allergic Disease, Jacob Sweeney '11

Honor Scholar Theses

In this thesis I will propose a novel framework for understanding allergy. I will argue that exposure to certain early-life environments lead to life-long allergic disease through epigenetic mechanisms. Although my argument currently exists as an unsubstantiated hypothesis, I will review indirect evidence that I have gathered throughout the immunologic and epigenetic literature to support my claim. | will then propose a set of experiments which will test my hypothesis. This thesis will address current scientific “hot topics” and their implications will challenge fundamental tenants of biology. Rather than jumping straight into the argument I will begin with some background …

Validation Of Methionine Aminopeptidase-1 As A Potential Chemotherapeutic Target For Leishmania Major, Elizabeth Calzada^, Carylinda Serna, Miguel A. Vasquez, Omonike Olaleye, Rosa Maldonado*

COURI Symposium Abstracts, Spring 2011

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Cutaneous leishmaniasis is a vector-borne disease caused by Leishmania major affecting millions of people throughout the world. It is an emerging concern in the United States due to military establishments in endemic countries. Treatment for the disease is highly toxic and the lack of vaccines emphasizes on the need for alternative drug treatments. Aminopeptidase inhibitors have shown promising results against malaria and tuberculosis. Methionine aminopeptadse-1 (MetAP1) catalyzes the removal of the N-terminal methionine residue from peptides and proteins. The human MetAP1 …

Cloning And Expression Of Methionine Aminopeptidase-1 From Trypanosoma Cruzi, Joshua A. Lara^, Miguel Vasquez, Rosa A. Maldonado*

COURI Symposium Abstracts, Spring 2011

Trypanosoma cruzi affects millions of people worldwide. This unicellular eukaryotic organism is the causative agent of Chagas’ disease. This blood-borne pathogen is transmitted to humans by the hemophagous triatomine or kissing bug. The high toxicity of existing treatments and the lack of vaccines clearly demonstrate the demand for new drugs to treat this parasitosis. We propose to target T. cruzi Methionine Aminopeptidase (TcMetAP1). This enzyme catalyzes the removal of the N-terminal amino acid residues from peptides and proteins. Recent studies have shown promising results of MetAP1 inhibitors against malaria. We, therefore, hypothesize that specific inhibitors of the parasitic MetAP1 will …

Isolation By Distance Explains Genetic Structure Of Buggy Creek Virus, A Bird-Associated Arbovirus, Abinash Padhi, Amy T. Moore, Mary Bomberger Brown, Jerome E. Foster, Martin Pfeffer, Charles R. Brown

School of Natural Resources: Faculty Publications

Many of the arthropod-borne viruses (arboviruses) show extensive genetic variability and are widely distributed over large geographic areas. Understanding how virus genetic structure varies in space may yield insight into how these pathogens are adapted to and dispersed by different hosts or vectors, the relative importance of mutation, drift, or selection in generating genetic variability, and where and when epidemics or epizootics are most likely to occur. However, because most arboviruses tend to be sampled opportunistically and often cannot be isolated in large numbers at a given locale, surprisingly little is known about their spatial genetic structure on the local …

Assessment Of Pathways For The Introduction And Spread Of Mycobacterium Bovis In The United States, Katie Portacci, Jason Lombard, Lauren Abrahamsen, Eric Bush, Charles Fossler, Robert Harris, Kamina Johnson, Ryan S. Miller, Dianna Mitchell, Randy Pritchard, Steven Sweeney, Todd Weaver

Zoonotics and Wildlife Disease: Publications

Bovine tuberculosis (TB) was responsible for more losses among U.S. farm animals in the early 20th century than all other infectious diseases combined. The Cooperative State-Federal Tuberculosis Eradication Program (established in 1917 and administered by APHIS, State animal health agencies, and U.S. livestock producers) has nearly eradicated bovine TB from the nation’s livestock population. However, despite the many accomplishments of the program, bovine TB remains a serious and costly disease of livestock in the United States. In 1992, VS conducted an assessment to identify pathways for the introduction and spread of bovine TB, in order to develop the most effective …

Targeted Drug-Resistance Testing Strategy For Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008, Gustavo E. Velásquez, Martin Yagui, J Peter Cegielski, Luis Asencios, Jaime Bayona, Cesar Bonilla, Hector O. Jave, Gloria Yale, Carmen Suárez, Sidney Atwood, Carmen C. Contreras, Sonya S. Shin

Dartmouth Scholarship

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005–November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household …

Low Levels Of Hydrogen Peroxide Stimulate Corneal Epithelial Cell Adhesion, Migration, And Wound Healing, Qing Pan, Wen-Ya Qiu, Ya-Nan Huo, Yu-Feng Yao, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. Intracellular reactive oxygen species have been reported to associate with growth factor and integrin signalings in promoting cell adhesion in many cell types. This study is to explore if exogenous H2O2 at low levels can be beneficial to cell adhesion, migration, and wound healing.

METHODS. Primary rabbit corneal epithelial cells treated with 0–70 M H2O2 were tested for viability by MTT assay, adhesion by centrifugation assay, focal contacts of vinculin and F-actin by immunofluorescence, activated Src(pY416), EGF receptor (pY845), vinculin(pY1065), FAK(pY397), and FAK(pY576) by immunoblotting. Cell migration was examined with 0–50 M H2O2 using the scratch wound technique. Corneal …

Imaging—And Imagining—Immune Responses To Infections, Kamal M. Khanna, Leo Lefrancois

UCHC Articles - Research

The use of sophisticated microscopy continues apace in analysis of infection and the induction of immune responses. Continued technological improvements in microscopy, fluorescent dyes, and transgenic reporter systems will allow constant improvements of our view of the microbial and immunological landscape. Understanding how anatomy, cellular movement and microbial pathogenesis are linked to the outcome of the immune response will allow us to make informed decisions regarding vaccine formulations and treatments for infectious diseases and their sequelae.

Fascin1 Promotes Cell Migration Of Mature Dendritic Cells, Michael Lipscomb

Department of Biology Faculty Publications

Dendritic cells (DCs) play central roles in innate and adaptive immunity. Upon maturation, DCs assemble numerous veil-like membrane protrusions, disassemble podosomes, and travel from the peripheral tissues to lymph nodes to present Ags to T cells. These alterations in morphology and motility are closely linked to the primary function of DCs, Ag presentation. However, it is unclear how and what cytoskeletal proteins control maturation-associated alterations, in particular, the change in cell migration. Fascin1, an actin-bundling protein, is specifically and greatly induced upon maturation, suggesting a unique role for fascin1 in mature DCs. To determine the physiological roles of fascin1, we …

Antibodies Elicited In Response To Ebna-1 May Cross- React With Dsdna, Pragya Yadav, Hoa Tran, Roland Ebegbe, Paul Gottlieb, Hui Wei, Rita H. Lewis, Alice Mumbey-Wafula, Atira Kaplan, Elina Kholdarova, Linda Spatz

Publications and Research

Background:Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the complete EBNA-1 protein can develop antibodies to double stranded DNA (dsDNA). The present study was undertaken to understand why anti-dsDNA antibodies arise during the immune response to EBNA-1.

Methodology/Principal Findings: In this study, we demonstrated that mouse antibodies elicited in response to EBNA-1 cross-react with dsDNA. First, we showed that adsorption of sera reactive with EBNA-1 and dsDNA, on dsDNA cellulose …

Influenza Nucleoprotein Interactions As Potential Antiviral Targets, Abel Sanchez

Theses Digitization Project

The purpose of this research was to investigate the Nucleoprotein (NP) RNA dependent RNA polymerase (RdRP) interaction by identifying and characterizing a NP mutant which maintains RNA binding but is unable to interact with the viral polymerase complex. Influenza poses a threat to human health and is a burden on the global economy. Influenza is caused by influenza virus which contains a segmented RNA genome, resulting in rapid evolution and emergence of new influenza subtypes which lead to pandemics.

Utilization Of A Custom-Designed Microbiota Array To Determine The Distal Gut Microbiota Of Healthy Human Adults, Richard Thomas Agans

Browse all Theses and Dissertations

The human microbiota is an essential component of human health and disease. It is involved in metabolism of dietary components and is at the forefront of the intestinal immune response. Classical techniques applied to study intestinal microbiota illustrated higher presences of aerobic and facultative-anaerobic bacteria, however; the levels of obligate anaerobes had been underrepresented. Modern technologies based on DNA and RNA analysis have circumvented previous challenges allowing researchers to gain more extensive insight into the complex intestinal environment. In this work, a recently developed Microbiota Array was used to assess intestinal microbiota of 10 healthy adults (age 22-61, ave. 34.3yrs). …

Identification Of The Role Of The Sal Locus In Streptococcus Pyogenes Virulence During Host-Pathogen Interactions, Phanramphoei Namprachan-Frantz

Wayne State University Dissertations

The pathogenesis of Streptococcus pyogenes is due to its ability to overcome and adapt to the harsh environment created by the host immune response. The focus of this project was the SalKR two-component regulatory system, which facilitates bacterial adaptation by responding to environmental signals during host pathogen-interactions. The first goal of this project was to determine a role in virulence for the SalKR regulatory system. The complete deletion of the salKR genes in the wild type S. pyogenes strain HSC5 produced a highly attenuated mutant in a Zebrafish infection model. The ΔsalKR mutant appeared to lose the ability to survive …

Going Viral, Judy Diamond

World of Viruses

Science education is developing new and innovative means of communication that compete directly with global media to reach the ‘YouTube Generation’. The truly interdisciplinary team of the SEPA-funded World of Viruses project is discovering how best to spread the word.

KEY COLLABORATORS
Judy Diamond, Professor, University of Nebraska State Museum
Charles Wood, Director, Nebraska Center for Virology
Moira Rankin, President, Soundprint Media Center, Inc
Carl Zimmer, Science writer and author of WoV book of essays, A Planet of Viruses
David Uttal, Cognitive science professor, Northwestern University
Benjamin Jee, Cognitive scientist, College of Holy Cross
Tom Floyd, Comic illustrator, Nebraska Educational …

Nematode Parasites Of Costa Rican Snakes (Serpentes) With Description Of A New Species Of Abbreviata (Physalopteridae), Charles R. Bursey, Daniel R. Brooks

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Seventy-eight snakes collected in the Area de Conservación Guanacaste, Costa Rica were necropsied: Boidae (1 species), boa constrictor, Boa constrictor; Colubridae (21 species), Ecuador sipo, Chironius grandisquamis; road guarder, Conophis lineatus; South American forest racer, Dendrophidion percarinatus; speckled racer, Drymobius margaritiferus; mimic false coral snake, Erythrolamprus mimus; blunthead tree snake, Imantodes cenchoa; western tree snake, Imantodes inornatus; banded cat-eyed snake, Leptodeira annulata; striped lowland snake, Leptodrymus pulcherrimus; Cope’s parrot snake, Leptophis depressirostris; yellow-bellied racer, Liophis epinephelus; neotropical whip snake, Masticophis mentovarius; brown vinesnake, Oxybelis aeneus; …

Estimating The Impact Of Human Papillomavirus (Hpv) Vaccination On Hpv Prevalence And Cervical Cancer Incidence In Mali, Leree Tracy, Holly Gaff, Colleen Burgess, Samba Sow, Patti E. Gravitt, J. Kathleen Tracy

Biological Sciences Faculty Publications

Human papillomavirus vaccines have potential to reduce cervical cancer incidence and mortality; however, cultural and economic barriers may hinder success in developing countries. We assessed impact of a single vaccine campaign in Mali with use of mathematical modeling. Our model shows that decreases in the prevalence of Human papillomavirus infection are proportional to achieved vaccination coverage.

The Impact Of Infectious Disease On Chronic Disease: A Review Of Contemporary Findings, Wendy Bjerke

All PTHMS Faculty Publications

Infectious diseases are among the top causes of death in adults and children. Chronic diseases such as cardiovascular disease and cancer are among the top causes of death in adults. Associations between bacterial and viral infectious agents and subsequent development of chronic disease have been made in the past but are currently being reexamined with more rigor and specificity. This review examines infectious disease agent causes and associations with cancer, cardiovascular disease, metabolic disease, and neurodegenerative disease. These associations will impact future research, surveillance, treatment, and prevention of both infectious and chronic diseases.

Roles Of The 15-Kda Selenoprotein (Sep15) In Redox Homeostasis And Cataract Development Revealed By The Analysis Of Sep 15 Knockout Mice, Marina V. Kasaikina, Dmitri E. Fomenko, Vyacheslav M. Labunskyy, Salil A. Lachke, Wenya Qiu, Juliet A. Moncaster, Jie Zhang, Mark W. Wojnarowicz, Sathish Kumar Natarajan, Mikalai I. Malinouski, Ulrich Schweizer, Petra A. Tsuji, Bradley A. Carlson, Richard L. Maas, Marjorie F. Lou, Lee E. Goldstein, Dolph L. Hatfield, Vadim N. Gladyshev

School of Veterinary and Biomedical Sciences: Faculty Publications

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable …

The Impact Of Tricaine Methanesulfonate, 2-Phenoxyethanol, And Carvone-Methyl Salicylate On The Innate Immune Response Of Zebrafish (Danio Rerio), Charles R. Wulff

Honors Theses

Anesthesia plays a vital role in the maintenance of aquaculture species, where it is used to minimize stress during complex handling tasks such as transport, assessment, and harvesting. However, anesthetics have been shown to suppress the innate immune response, which could impact immunity and increase risk of infection. Tricaine methanesulfonate (MS-222) and 2-Phenoxyethanol (2-PE) represent two of the most commonly used anesthetics in aquaculture, with R-(+)-carvone, in the form of carvone-methyl salicylate (CMS) has recently been proposed as an alternative anesthetic for food fish. These three anesthetics were used to assess the influence of anesthetics on the immune system of …

Role Of Pi3k-Akt Pathway In The Age Associated Decline In Tlr Mediated Activation Of Innate And Adaptive Immune Responses, Mosoka Papa Fallah

University of Kentucky Doctoral Dissertations

Immunosenescence results in reduced immune response to infections with Streptococcus pneumoniae as well as to pneumococcal polysaccharide vaccines. The antibody response to the capsular polysaccharide (CPS) provides protection against S. pneumoniae infection. CPS immunoresponse is T cell independent and needs the macrophage-derived cytokines such as IL-12, IL-6 and IL-1β to elicit an antibody response. We showed a cytokine dysregulation, i.e. a decrease in IL-12, IL-6 and TNF-α but an increase in IL-10, in the aged (18-24 months old comparable to >65 years in human) compared to young adult mouse (8-12 weeks less than 65 years old) splenic macrophages (SM) or …

Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang

Legacy Theses & Dissertations (2009 - 2024)

Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …

American Society Of Parasitologists Newsletter, V. 33, Nos. 1 & 2, 2011, Scott Lyell Gardner

American Society of Parasitologists: Newsletter

An issue of the American Society of Parasitologists Newsletter, also known as the Newsletter of the Journal of Parasitology.

Analysis Of The Streptococcal Cpsa Protein In Dna-Binding And Regulation Of Capsule And Cell Wall Maintenance, Brett R. Hanson

Wayne State University Dissertations

The systemic pathogens Streptococcus agalactiae (GBS) and Streptococcus pneumoniae remain a significant threat to human health worldwide. The ability of these organisms to cause systemic disease is compounded by the production of a polysaccharide capsule that provides immune evasion function. The production of the polysaccharide capsule in systemic streptococcal pathogens is controlled in part by the membrane bound protein CpsA. These studies analyze the contribution of CpsA to regulation of capsule level in the model aquatic pathogen Streptococcus iniae and human specific pathogen GBS, and how this regulation affects virulence in in-vitro, ex-vivo, and in-vivo models of pathogenesis. We have …

Calf Pre-Weaning Traits And Immunoglobulin Response To Bovine Viral Diarrhea Virus Vaccination, Whitney Downum, A. Hayden Brown Jr., Jeremey G. Powell, E. Beth Kegley, Zelpha B. Johnson, Doug B. Galloway, James A. Hornsby, Billy R. Lindsey

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Calfhood vaccination for bovine viral diarrhea virus (BVDV) is a relatively new concept, and protocols are evolving. Our objective was to determine effects of BVDV type I vaccination protocol, calf behavior (chute score, and chute exit velocity), and gender on calf gain and immunoglobulin (Ig) response. Crossbred calves (n = 64) were randomly allotted to one of two vaccination protocols. In protocol 1, calves were vaccinated at 60 d of age (d 0) and at weaning (d 147). Calves assigned to protocol 2 were vaccinated against BVDV type I at 21 d prior to (d 126) and at weaning (d …

Mechanism For Pre-B Cell Loss In Mutant Ali/Ali Rabbits, Gregory Robert Robbins

Dissertations

Pre-B cell receptor (pre-BCR) signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional μ-chains undergo selective expansion. My dissertation work used a rabbit model system to study how VH structure affects the early stages of B cell development in the bone marrow (BM). Developing B cells in mutant ali/ali rabbits predominantly utilize VH4 during VDJ gene rearrangement. However, most of the VH4-utilizing B cells encounter a severe block early in B cell development. In contrast, wildtype rabbit B cells predominantly rearrange VH1, a gene >90% identical to VH4, and develop normally. We hypothesized that …

Efficacy Of The Pentavalent Rotavirus Vaccine, Rotateq (Rv5), Between Doses Of A 3-Dose Series And With Less Than 3 Doses (Incomplete Regimen), Penelope D. Dennehy, Timo Vesikari, David O. Matson, Robbin F. Itzler, Michael J. Dallas, Michelle G. Goveia, Mark J. Dinubile, Penny M. Heaton, Max Ciarlet

Community & Environmental Health Faculty Publications

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the …

The Innate Anti-Hiv-1 Activity Of Human Seminal Plasma, Julie A. Martellini-Moore

Electronic Theses and Dissertations

Human immunodeficiency virus (HIV) has become a global pandemic over the past few decades, with new infections and related deaths in the millions each year. There is no cure in sight for HIV-1 infection, and there has been little progress in developing an efficacious vaccine. Heterosexual transmission of HIV-1 remains the principal mode of transmission throughout the world and thus measures, such as topical vaginal microbicides, to prevent infection of the female reproductive tract are actively being explored. Recent trials of topical vaginal microbicides have shown that their interaction with the mucosal surfaces of the female reproductive tract as well …

Preventing Mother-To-Child Transmission Of Human Immunodeficiency Virus-1 (Hiv-1): Effects Of Intrapartum And Neonatal Single-Dose Nevirapine Prophylaxis And Subsequent Hiv-1 Drug Resistance At Antiretroviral Treatment Initiation, Amanda L. Harmon

CMC Senior Theses

The prevention of mother-to-child transmission is one of the most powerful tools in human immunodeficiency virus type 1 (HIV-1) prevention and has huge potential to improve both maternal and child health. In the absence of any preventative measures, infants born to and breastfed by their HIV-positive mothers have roughly a one-in-three chance of acquiring the infection themselves. HIV can be passed on from mother-to-child during pregnancy, during labor and delivery, and even after during breastfeeding.

Intrapartum and neonatal single-dose nevirapine (sd-NVP) is the foundation of preventing mother-to-child transmission in lower resource settings where it has been used alone or as …

The Role Of Hiv-1 Proteins In Alzheimer's Disease Pathology, Brian Nelson Giunta

USF Tampa Graduate Theses and Dissertations

Prevalence of HIV-associated cognitive impairment is rising, the worst form of which is HIV-associated dementia (HAD). The disease is fuiled by a chronic innate type pro-inflammatory response in the brain which is highly dependent upon the activation of microglia. We first created an in vitro model of HAD composed of cultured microglial cells synergistically activated by the addition of IFN-gamma and the HIV-1 coat glycoprotein, gp120. This activation, as measured by TNF-alpha and NO release, is synergistically attenuated through the alpha7nAChR and p44/42 MAPK system by pretreatment with nicotine, and the cholinesterase inhibitor, galantamine. As these medications have been FDA …