Immunology and Infectious Disease Commons^™

The Conserved G-Protein Coupled Receptor Fshr-1 Regulates Protective Host Responses To Infection And Oxidative Stress, Elizabeth V. Miller, Leah N. Grandi, Jennifer A. Giannini, Joseph D. Robinson, Jennifer R. Powell

Biology Faculty Publications

The innate immune system’s ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. InCaenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation …

Role Of Macrophages In Muscle Transfection With Pdna/Pluronic Formulation, Vivek Mahajan

Theses & Dissertations

Non-ionic amphiphilic block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), Pluronics, arranged in a tri-block structure PEO-PPO-PEO, have raised a considerable interest in skeletal muscle Gene Therapy. Previous studies have demonstrated that co-administration of Pluronics with naked plasmid DNA (pDNA) by direct i.m. injection enhanced transgene expression not only in muscle but also in distal lymphoid organs (spleen and lymph nodes) and this response was strain-dependent; not observed in athymic (BALB/c nu/nu) mouse; suggesting a role of immune cells in gene transfer to skeletal muscles. Therefore, we first evaluated the role of inflammation and inflammatory cells, on muscle …

Proteins Of Bartonella Bacilliformis:Candidates For Vaccine Development, Cesar Henriquez-Camocho, Palmira Ventosilla, Michael F. Minnick, Joaquim Ruiz, Ciro Maguina

Biological Sciences Faculty Publications

Bartonella bacilliformis is the etiologic agent of Carrion's disease suggest complex adaptations by the bacterium to the human host, with the overall objectives of persistence, maintenance of a reservoir state for vectorial transmission, and immune evasion. These events include a multitude of biochemical and genetic mechanisms involving both bacterial and host proteins. This review focuses on proteins involved in interactions between B. bacilliformis and human host. Some of them (e.g., flagellin, Brps, IalB, FtsZ, Hbp/Pap31, and other outer membrane proteins) are potential protein antigen candidates for a synthetic vaccine.

Community-Acquired Methicillin-Resistant Staphylococcus Aureus (Ca-Mrsa) Usa300 Perturbs Acquisition Of Lysosomal Hydrolases And Requires Phagosomal Acidification For Survival In A Human Macrophage Cell Line, Zachary Ronald Tranchemontagne

All Theses And Dissertations

Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) strain USA300 is a major cause of invasive drug-resistant skin and soft tissue infections in humans. Although S. aureus is a well-recognized extracellular pathogen, recent reports that USA300 survives inside host macrophages suggest that the intramacrophage environment may be a niche for persistent infection. Intramacrophage survival requires bacteria to avoid destruction in the phagosome; however, mechanisms by which USA300 evades phagosomal defenses are unclear. We examined the fate of the USA300-containing phagosome in human THP-1 macrophages by evaluating phagosomal acidification and maturation, and by testing the impact of phagosomal conditions on bacterial viability. Utilizing confocal …

Geospatial Resolution Of Human And Bacterial Diversity With City-Scale Metagenomics, Ebrahim Afshinnekoo, Cem Meydan, Shanin Chowdhury, Dyala Jaroudi, Collin Boyer, Nick Bernstein, Julia M. Maritz, Darryl Reeves, Jorge Gandara, Sagar Chhangawala, Sofia Ahsanuddin, Amber Simmons, Timothy Nessel, Bharathi Sundaresh, Elizabeth Pereira, Ellen Jorgensen, Sergios-Orestis Kolokotronis, Nell Kirchberger, Isaac Garcia, David Gandara, Sean Dhanraj, Tanzina Nawrin, Yogesh Saletore, Noah Alexander, Priyanka Vijay, Elizabeth M. Hénaff, Paul Zumbo, Michael Walsh, Gregory D. O'Mullan, Scott Tighe, Joel T. Dudley, Anya Dunaif, Sean Ennis, Eoghan O'Halloran, Tiago R. Magalhaes, Braden Boone, Angela L. Jones, Theodore R. Muth, Katie Schneider Paolantonio, Elizabeth Alter, Eric E. Schadt, Jeanne Garbarino, Robert J. Prill, Jane M. Carlton, Shawn Levy, Christopher E. Mason

Publications and Research

The panoply of microorganisms and other species present in our environment influence human health and disease, especially in cities, but have not been profiled with metagenomics at a city-wide scale. We sequenced DNA from surfaces across the entire New York City (NYC) subway system, the Gowanus Canal, and public parks. Nearly half of the DNA (48%) does not match any known organism; identified organisms spanned 1,688 bacterial, viral, archaeal, and eukaryotic taxa, which were enriched for harmless genera associated with skin (e.g., Acinetobacter). Predicted ancestry of human DNA left on subway surfaces can recapitulate U.S. Census demographic data, and bacterial …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Behavioral Immunity Suppresses An Epizootic In Caribbean Spiny Lobsters, Mark J. Butler Iv, Donald C. Behringer Jr., Thomas W. Dolan Iii, Jessica Moss, Jeffrey D. Shields

Biological Sciences Faculty Publications

Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of "behavioral immunity"; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Nsf Grant Helps Preserve Parasite Collections [Press Release], Scott Gardner, Leslie Reed

Scott L. Gardner Publications

The National Science Foundation has awarded a $500,000 grant that will allow four major parasite collections to be digitized. The collections are part of UNL's Harold W. Manter Laboratory of Parasitology. Scott Gardner (pictured) is the curator and director of the Manter Laboratory.

A $500,000 grant from the National Science Foundation will allow the Harold W. Manter Laboratory of Parasitology to digitally preserve four major collections of parasite specimens donated to the University of Nebraska-Lincoln during the past five years.

Detection Of Hcmv Viral Il-10 (Vil-10) In Healthy Blood Donors, Vivian P. Young

Master's Theses

Human cytomegalovirus (HCMV) is widespread in the general population and can establish lifelong latency with expression of a limited subset of viral genes. The UL111A gene is expressed during both lytic and latent infection, and at least two protein isoforms are produced. During lytic infection, the full length transcript yields cmvIL-10, a potent immunosuppressive viral ortholog of human IL-10 (hIL-10). Alternative splicing of the UL111A transcript yields a truncated protein, LAcmvIL-10, which is expressed during both lytic and latent infection but with a limited range of immunosuppressive functions. The two viral cytokines, collectively termed viral IL-10 (vIL-10), are identical in …

Draft Genome Sequences Of Six Different Staphylococcus Epidermidis Clones, Isolated Individually From Preterm Neonates Presenting With Sepsis At Edinburgh's Royal Infirmary, Paul Walsh, M. Bekaert, J. Carroll, T. Manning, B. Kelly, A. O'Driscoll, X. Lu, C. Smith, P. Dickinson, K. Templeton, P. Ghazal, Roy D. Sleator

Department of Biological Sciences Publications

Herein, we report the draft genome sequences of six individual Staphylococcus epidermidis clones, cultivated from blood taken from different preterm neonatal sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom.

Parasite Infection Mediates Trait Tradeoffs In Fundulus Heteroclitus, Sarah Dunn

Honors College Theses

To be successful, an animal must eat, grow, and reproduce. With limited resources, there are tradeoffs between these critical life history parameters but the direction of the tradeoffs is largely unknown in a changing environment. To determine whether environmental context affects life-history tradeoffs, I surveyed and quantified investment into reproduction, growth, and a proxy for immunity (parasitism), in the mummichog, Fundulus heteroclitus, a common inhabitant of salt marshes in Georgia. Three salt marsh sites along coastal Georgia (Shellman Bluff, Skidaway Island, and Tybee Island) were selected using a proxy for anthropogenic disturbance (impervious surface), which also fell along a …

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …

The Regulation Of Cathepsin L Activity By Estrogen And Bisphenols A & S: Relationship To Systemic Lupus Erythematosus, Dylan T. Cuva

Biology Honors Papers

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that is linked to increased levels of estrogen. Bisphenol A (BPA) is an environmental estrogen that may also play a role in SLE. BPA is used in the production of polycarbonate plastics and epoxy resins, including use in the creation of cans and plastic bottles. This study investigated the role of BPA and other bisphenols on enzyme activity in a murine model for SLE.

The Effects Of Digestion On Innate Immunity, Rachel L. Luoma

Honors College Theses

Following a meal, an animal can exhibit dramatic shifts in its physiology that can result in rapid growth of the gut and heart, as well as a massive (>40-fold) increase in metabolic rate associated with the energetic costs of processing the meal. However, little is known about the effects of digestion on an important physiological trait: immune function. Thus, I tested the following competing hypotheses. First, digesting animals may upregulate their immune systems due to increased microbial exposure from ingested food. This hypothesis predicts that animals will exhibit greater immune function during digestion. Second, digesting animals may downregulate their …

Tcr Alpha Lcr And Non-Lcr Cis-Elements Contributing To Tissue Specific Expression Of The Tcr Alpha Gene In Thymic And Peripheral T Cells, Martina Kucerova-Levisohn

Dissertations, Theses, and Capstone Projects

Orchestrated expression of multiple genes residing in the complex TCRα/δ/Dad1 locus requires tight control from multiple cis-acting elements. The TCRα locus control region (LCR), is positioned between TCRα and Dad1 gene, and has been implicated in the differential expression of both genes. In this study, we focus our work on the hypersensitive site (HS)1 prime (HS1'), located 3' of the classical Eα enhancer, within the TCRα LCR. We investigated its non- redundant role in TCRα expression in thymic and peripheral T cells as assayed by in vivo and in vitro studies. Furthermore, formation of HS1' in both lymphoid and …

Effects Of Urbanization On The Occurrence Of Batrachochytrium Dendrobatidis: Do Urban Environments Provide Refuge From The Amphibian Chytrid Fungus?, Daniel Saenz, Taylor L. Hall, Matthew Kwiatkowski

Faculty Publications

Batrachochytrium dendrobatidis (Bd) is a widespread pathogenic fungus that is known to cause the disease, chytridiomycosis, which can be lethal to many amphibians. We compared occurrence rates on spring peepers (Pseudacris crucifer) in urban and forested breeding sites in eastern Texas, USA. All study sites were at approximately the same latitude and altitude, and samples were collected at the same time of year to isolate differences in Bd infection rates between habitat types. We found significant differences (p<0.001) in the occurrence of Bd between habitats; with dramatically lower rates of occurrence at urban sites (19.5 %), compared to forested sites (62.9 …

The Loss Of Genomic Uracil Homeostasis And Aid-Dependent Accumulation Of Dna Damage In B Cell Lymphomas, Sophia Shalhout

Wayne State University Dissertations

Activation-induced deaminase (AID) is a sequence-selective DNA cytosine deaminase that introduces uracils in immunoglobulin genes. This DNA mutator is required for somatic hypermutation and class switch recombination- processes involved in the affinity maturation and diversification of antibodies. AID, however, can also lead to deleterious mutations and translocations promoting lymphomagenesis. The introduction of uracils throughout the genome of activated B cells and the ability of UNG2 glycosylase to excise these uracils is examined here. This interplay was also studied in cancerous B cells, with different results emerging in transformed cells versus healthy cells. Genomic uracil levels are found to remain at …

Comparative Population Genetics Of Two Invading Ticks: Evidence Of The Ecological Mechanisms Underlying Tick Range Expansions, Robyn Nadolny, Holly Gaff, Jens Carlsson, David Gauthier

Biological Sciences Faculty Publications

Two species of ixodid tick, Ixodes affinis Neumann and Amblyomma maculatum Koch, are simultaneously expanding their ranges throughout the mid-Atlantic region of the US. Although we have some understanding of the ecology and life history of these species, the ecological mechanisms governing where and how new populations establish and persist are unclear. To assess population connectivity and ancestry, we sequenced a fragment of the 16S mitochondrial rRNA gene from a representative sample of individuals of both species from populations throughout the eastern US. We found that despite overlapping host preferences throughout ontogeny, each species exhibited very different genetic and geographic …

Antibodies To Pseudogymnoascus Destructans Are Not Sufficient For Protection Against White-Nose Syndrome, Joseph S. Johnson, Deeann M. Reeder, Thomas M. Lilley, Ken Field

Faculty Journal Articles

White-nose syndrome (WNS) is a fungal disease caused by Pseudogymnoascus destructans (Pd) that affects bats during hibernation. Although millions of bats have died from WNS in North America, mass mortality has not been observed among European bats infected by the fungus, leading to the suggestion that bats in Europe are immune. We tested the hypothesis that an antibody-mediated immune response can provide protection against WNS by quantifying antibod- ies reactive to Pd in blood samples from seven species of free-ranging bats in North America and two free-ranging species in Europe. We also quantified antibodies in blood samples from little brown …

An Examination Of Mathematical Models For Infectious Disease, David M. Jenkins

Williams Honors College, Honors Research Projects

Starting with the original 1926 formulation of the SIR (Susceptible-Infected-Removed) model for infectious diseases, mathematical epidemiology continued to grow. Many extensions such as the SEIR, MSIR, and MSEIR models were developed using SIR as a basis to model diseases in a variety of circumstances. By taking the original SIR model, and reducing the system of three first-order equations to a single first-order equation, analysis shows that the model predicts two possible situations. This analysis is followed by discussion of an alternative use of the SIR model which allows for one to track the amount of sustainable genetic variation in a …

Zymosan Activation Of Tlrs: Stimulation Of Innate Immunity And Nitric Oxide Production, Sarah Loeser

Williams Honors College, Honors Research Projects

Chronic inflammation can result in pathophysiological changes to numerous organs of the body such as heart tissue (atherosclerosis) and damage to bone. Sources of inflammation can include autoimmune disease, cancer, and chronic infections such as those triggered by HIV or Mycobacterium tuberculosis. Most of the damage associated with chronic inflammation can be associated with chemical mediators, cytokines, given off by cells of the innate immune system. One measure of an active innate immune system can be assessed by quantifying nitric oxide (NO) production by bone marrow (BM) cells.

The purpose of these experiments is to determine if zymosan, a …

Mmv Malaria Box Activity Screening In Dormant Plasmodium Falciparum Phenotypes, Sandra Galusic

USF Tampa Graduate Theses and Dissertations

The causative agent of malignant tertian malaria, Plasmodium falciparum undergoes an arrested growth phenotype of its erythrocytic stage when under drug-stress. Recent artemisinin treatment failures seem to be indicative of such induction followed by recrudescence rather than actual therapeutic failure. Likewise, P. vivax hypnozoites are the prototypic dormants and the latent infections for which they are responsible prove most difficult to treat. Dihydroartemisinin, an artemisinin-derivative, can be used to exploit this mechanism by inducing a dormant state in ring-stage P. falciparum parasites and in turn, their recovery may be used as a screening period for compounds that inhibit or foster …

Impacts Of Agrochemical Pollution On Aquatic Communities And Human Disease, Neal T. Halstead

USF Tampa Graduate Theses and Dissertations

The global human population is expected to exceed 9 billion individuals by 2050, putting greater strain on the natural resources needed to sustain such a population. To feed this many people, some expect agricultural production will have to double and agrochemical use will have to increase anywhere from two- to five-fold relative to the turn of the century. Although industrial agriculture has provided many benefits to society, it has caused declines in biodiversity, both directly (e.g., through conversion of habitat) and indirectly (e.g., through contamination of adjacent natural habitats). Agricultural activity has also been linked to increased prevalence and intensity …

Transmission-Blocking Vaccines: Focus On Anti-Vector Vaccines Against Tick-Borne Diseases, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Tick-borne diseases are a potential threat that account for significant morbidity and mortality in human population worldwide. Vaccines are not available to treat several of the tick-borne diseases. With the emergence and resurgence of several tick-borne diseases, emphasis on the development of transmission-blocking vaccines remains increasing. In this review, we provide a snap shot on some of the potential candidates for the development of anti-vector vaccines (a form of transmission-blocking vaccines) against wide range of hard and soft ticks that include Ixodes, Haemaphysalis, Dermacentor, Amblyomma, Rhipicephalus and Ornithodoros species.

Mutations In The Plasmodium Falciparum Chloroquine Resistance Transporter, Pfcrt, Enlarge The Parasite's Food Vacuole And Alter Drug Sensitivities, Serena Pulcini, Henry M. Staines, Andrew H. Lee, Sarah H. Shafik, Guillaume Bouyer, Catherine M. Moore, Daniel A. Daley, Matthew J. Hoke, Lindsey M. Altenhofen, Heather J. Painter, Jainbing Mu, David J.P. Ferguson, Manuel Llinás, Rowena E. Martin, David A. Fidock, Roland A. Cooper, Sanjeev Krishna

Biological Sciences Faculty Publications

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction …

A New Laelapine Mite (Acari: Mesostigmata: Laelapidae) Associated With The Spiny Rodent, Scolomys Melanops, In Amazonian Peru, Donald Gettinger, Scott L. Gardner

Scott L. Gardner Publications

Gigantolaelaps scolomys Gettinger and Gardner n. sp., an ectoparasitic mite (Acari: Laelapidae) associated with the rodent Scolomys melanops in Amazonian forests of Peru, is described and illustrated.

Mites of the genus Gigantolaelaps Fonseca are common ectoparasites associated exclusively with rodents of the sigmodontine tribe Oryzomyini (see Gettinger, 1987). They are often abundant in the dorsal pelage and are easily collected by brushing the host at capture. The laelapine populations sampled are female dominant; males and immatures are assumed to live within the nest of the host (Martins-Hatano et al., 2011). A new species was encountered in a small collection of …

Development And Maintenance Of Thymic Epithelial Microenvironment, Varan J. Singh

Dissertations and Theses

Thymus is a primary lymphoid organ responsible for proper development and selection Of T-­‐cells. The thymic microenvironment, however, undergoes age related involution, Resulting in a reduction of the repertoire of T-­‐cells that are produced, and a decreased Capacity to respond to new antigen. Even though significant thymic epithelial turnover occurs, it is unclear if postnatal thymic progenitors/stem cell are responsible for the maintenance of the TEC microenvironment. Here we use the K5rtTA:TetO-­‐H2BGFP transgenic model to identify a slow cycling potential stem cells/progenitor population in the postnatal thymus. These cells were isolated, expanded in culture, and successfully differentiated into adipocytes, chondrocytes …

Serine Palmitoyltransferase And Giardial Encystation, Monica Delgado

Open Access Theses & Dissertations

Giardia lamblia is a flagellated protozoan parasite responsible for chronic diarrheal disease in humans and animals. Giardia has minimal lipid synThesis machinery and the majority of its lipids are obtained from the small intestine of humans where the trophozoites colonize. Recent results from our laboratory indicate that sphingolipids (SLs) are also important for Giardia and they regulate encystation and cyst production. Only five SL genes are present in this parasite and they are differentially regulated during encystation. In my studies, I found that giardial serine palmitoyltransferase (gSPT) activity is upregulated in encysting cells, suggesting it might play an important role …

Efficacy And Resistance Potential Of Jpc-3210 In Plasmodium Falciparum, Siobhan Marie Flaherty

USF Tampa Graduate Theses and Dissertations

Combating drug resistant malaria has been historically challenging, and remains so today. Recent reports from Southeast Asia show that Plasmodium falciparum is developing resistance to even our best defenses; artemisinin-based therapies. This development threatens to become a significant challenge in controlling malaria infections worldwide, making research into developing and characterizing new antimalarial drugs increasingly important. The purpose of this study was to characterize the resistance potential of novel antimalarial compound JPC-3210 in vitro using P. falciparum clones. JPC-3210 is a new long acting drug with potential to be used in combination with fast-acting drugs like artemisinins to cure drug resistant …