Immunology and Infectious Disease Commons^™

Molecular Assessment Of Bacterial Vaginosis By Lactobacillus Abundance And Species Diversity, Joke A. M. Dols, Douwe Molenaar, Jannie J. Van Der Helm, Martien P. M. Caspers, Alie De Kat Angelino-Bart, Frank H. J. Schuren, Adrianus G. C. L. Speksnijder, Hans V. Westerhoff, Jan Hendrik Richardus, Mathilde E. Boon, Gregor Reid, Henry J. C. De Vries, Remco Kort

Microbiology & Immunology Publications

Background

To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods.

Methods

Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal …

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, …

Investigating The Efficacy And Anti-Resistance Activity Of Fexinidazole In Conjunction With Eflornithine Against Trypanosoma Brucei For Treatment Of Human African Trypanosomiasis, Mercy Toma

Selected Honors Theses

Human African Trypanosomiasis (HAT) is one of 17 neglected tropical disease prioritized by the World Health Organization (WHO). Neglected tropical diseases are diseases which affect poor or developing countries and which do not get as much as attention as the ‘big three’: malaria, tuberculosis and HIV/AIDS. HAT specifically affects coutries in Sub-Saharan Africa and is caused by a parasitic protozoa, Trypanosoma brucei. There are two stages of HAT: the early haemolymphatic and late meningo-encephalitic stages. There are also two subtypes of the disease caused by either T. b. gambiense or T.b rhodesiense forms of the parasite. There are four drugs …

Amp Expression In Energetic Hybrid D. Melanogaster Infected With P. Rettgeri, Cassandra K. Treu, Justin Buchanan, Kristi Montooth

UCARE: Research Products

The purpose of this experiment was to investigate immune function and energy metabolism, particularly the levels of antimicrobial peptides produced in Drosophila energetically compromised genotypes. This will provide the ability to investigate energetics of immunity without changing diet. Flies were infected with the bacteria P. rettgeri and the resulting immune response was investigated. Females did not mount as effective an immune response as males. All flies exhibited decreased survivorship from infection. Control flies survived at higher levels and showed no mitochondrial:nuclear interaction.

Patterns Of Olfactory Neurogenesis And Immune Response In Adult Zebrafish Following Damage Of The Olfactory Bulb, Darcy M. Trimpe

Dissertations

The adult zebrafish olfactory system, with its persistent neuronal turnover and abundant regenerative capacity, is an excellent model system for studies of adult brain plasticity. Reversible deafferentation, achieved by repeated intranasal irrigation with detergent, reduces bulbar innervation and affects bulb structure and function, while cessation of treatment permits reinnervation and recovery of bulb volume. Alterations in cell genesis may account for this phenomenon. This study focuses on adult neurogenesis in the zebrafish olfactory system following reversible deafferentation and direct olfactory bulb injury.

Potential alterations in cell proliferation, differentiation, migration, and survival in the olfactory bulb following single and repeated intranasal …

Targeting Histone Deacetylases In Melanoma And T-Cells To Improve Cancer Immunotherapy, Andressa Sodre De Castro Laino

USF Tampa Graduate Theses and Dissertations

Histone deacetylases (HDACs) are key mediators of gene expression and, thus, major regulators of cell function. As such, HDACs play a role in orchestrating tumor biology, and the use of small inhibitors targeting theses proteins is attractive for the field of cancer therapy. Indeed, several HDAC inhibitors have received FDA-approval for the treatment of malignancies, while a myriad of these compounds continue to be evaluated in clinical trials. Besides their direct impact on tumor growth, HDAC inhibitors have been shown to increase immunogenicity of cancer cells, facilitating generation of a productive immune response against tumors. Immunotherapeutic approaches take advantage of …

Identification And Characterization Of Ion Channel Activity Of The M2 Protein From Influenza Virus D (Dm2), Jianing Liu

School of Biological Sciences: Dissertations, Theses, and Student Research

Viral ion channels are membrane proteins of influenza viruses that play essential roles in the replication cycle, which enables them to be targeted by antiviral drugs. M2 of influenza type A virus, BM2 of influenza type B virus, and CM2 from influenza type C virus have been characterized as ion channel proteins and antiviral drug amantadine was developed to control influenza type A virus. However, few studies have been conducted to clarify the properties of the M2 protein (DM2) of influenza type D virus, a novel influenza virus genus identified in 2014. To identify the ion channel activity of DM2, …

Neglected Dimensions Of Global Security: The Global Health Risk Framework Commission, Lawrence O. Gostin, Carmen C. Mundaca-Shah, Patrick W. Kelley

Georgetown Law Faculty Publications and Other Works

The world has experienced global health crises ranging from novel influenzas (H5N1 and H1N1) and coronaviruses (SARS and MERS) to the Ebola and Zika viruses. In each case, governments and international organizations seemed unable to react quickly and decisively. Health crises have unmasked critical vulnerabilities— weak health systems, failures of leadership, and political overreaction and underreaction. The Global Health Risk Framework Commission, for which the National Academy of Medicine served as the secretariat, recently set out a comprehensive strategy to safeguard human and economic security from pandemic threats.

Analysis Of Johne's Disease Elisa Status And Associated Performance Parameters In Irish Dairy Cows, A. E. Kennedy, N. Byrne, A. B. Garcia, Jim O'Mahony, R. G. Sayers

Department of Biological Sciences Publications

Background

Infection with Mycobacterium avium subspecies paratuberculosis (MAP) has been associated with reductions in milk production in dairy cows and sub optimal fertility. The aim of this study was to highlight the production losses associated with testing MAP ELISA positive in Irish dairy cows. Secondary objectives included investigation of risk factors associated with testing MAP ELISA positive. A survey of management practices on study farms was also conducted, with examination of associations between management practices and herd MAP status.

Blood samples were collected from 4188 breeding animals on 22 farms. Samples were ELISA tested using the ID Screen Paratuberculosis Indirect …

Profiles Of Low Complexity Regions In Apicomplexa, Fabia U. Battistuzzi, Kristan A. Schneider, Matthew K. Spencer, David Fisher, Sophia Chadhry, Ananias A. Escalante

Harold W. Manter Laboratory of Parasitology: Library Materials

Background: Low complexity regions (LCRs) are a ubiquitous feature in genomes and yet their evolutionary history and functional roles are unclear. Previous studies have shown contrasting evidence in favor of both neutral and selective mechanisms of evolution for different sets of LCRs suggesting that modes of identification of these regions may play a role in our ability to discern their evolutionary history. To further investigate this issue, we used a multiple threshold approach to identify species-specific profiles of proteome complexity and, by comparing properties of these sets, determine the influence that starting parameters have on evolutionary inferences.

Results: …

Hyperactive Erk And Persistent Mtor Signaling Characterize Vemurafenib Resistance In Papillary Thyroid Cancer Cells, Elyse Hanly, Neha Y. Tuli, Robert B. Bednarczyk, Robert Suriano, Jan Geliebter, Augustine L. Moscatello, Zbigniew Darzynkiewicz, Raj K. Tiwari

NYMC Faculty Publications

Clinical studies evaluating targeted BRAFV600E inhibitors in advanced thyroid cancer patients are currently underway. Vemurafenib (BRAFV600E inhibitor) monotherapy has shown promising results thus far, although development of resistance is a clinical challenge. The objective of this study was to characterize development of resistance to BRAFV600E inhibition and to identify targets for effective combination therapy. We created a line of BCPAP papillary thyroid cancer cells resistant to vemurafenib by treating with increasing concentrations of the drug. The resistant BCPAP line was characterized and compared to its sensitive counterpart with respect to signaling molecules thought to be directly related to resistance. Expression …

Laelapine Mite (Acari: Laelapidae) Morphometric Analysis Reflects Taxonomic And Geographic Clusters Of South American Oryzomyines (Rodentia: Sigmodontinae), Donald Gettinger, Robert D. Owen

MANTER: Journal of Parasite Biodiversity

Ongoing efforts to survey and inventory nonvolant small mammals across the Neotropics are beginning to reveal a highly structured and diverse fauna of rodents and marsupials. By increasing the foundation of specimens in museums around the world, it has become possible, for the first time, to evaluate and quantify the similarities and differences among small mammals collected from a broad range of geographic locali­ties, ecoregions, and habitats. Because ectoparasites were sampled in the process of collecting mammalian voucher specimens, we are able to study the laelapine mites (Acari: Laelapidae) associated with well-iden­tified and verifiable host specimens. Here, we evaluate morphometric …

Dna Barcoding And Taxonomy: Dark Taxa And Dark Texts, Roderic D. M. Page

Harold W. Manter Laboratory of Parasitology: Library Materials

Both classical taxonomy and DNA barcoding are engaged in the task of digitizing the living world.Much of the taxonomic literature remains undigitized. The rise of open access publishing this century and the freeing of older literature from the shackles of copyright have greatly increased the online availability of taxonomic descriptions, but much of the literature of the mid- to late- twentieth century remains offline (‘dark texts’). DNA barcoding is generating a wealth of computable data that in many ways are much easier to work with than classical taxonomic descriptions, but many of the sequences are not identified to species level. …

Comparing Apples And Oranges?: Next Generation Sequencing And Its Impact On Microbiome Analysis, Adam G. Clooney, Fiona Fouhy, Roy D. Sleator, Aisling O'Driscoll, Stanton Catherine, Paul D. Cotter, Marcus J. Claesson

Department of Biological Sciences Publications

Rapid advancements in sequencing technologies along with falling costs present widespread opportunities for microbiome studies across a vast and diverse array of environments. These impressive technological developments have been accompanied by a considerable growth in the number of methodological variables, including sampling, storage, DNA extraction, primer pairs, sequencing technology, chemistry version, read length, insert size, and analysis pipelines, amongst others. This increase in variability threatens to compromise both the reproducibility and the comparability of studies conducted. Here we perform the first reported study comparing both amplicon and shotgun sequencing for the three leading next-generation sequencing technologies. These were applied to …

Incomplete Protection Against Dengue Virus Type 2 Re-Infection In Peru, Brett M. Forshey, Robert C. Reiner, Sandra Olkowski, Amy C. Morrison, Angelica Espinoza, Kanya C. Long, Stalin Vilcarromero, Wilma Casanova, Helen J. Wearing, Eric S. Halsey, Tadeusz J. Kochel, Thomas W. Scott, Steven T. Stoddard

Faculty Publications

© 2016 Public Library of Science. All Rights Reserved. Background: Nearly half of the world’s population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010–2011, 15 years after the first outbreak of DENV-2 in the region. Methodology/Principal Findings: We estimated the age-dependent prevalence …

Unique Features Of A Global Human Ectoparasite Identified Through Sequencing Of The Bed Bug Genome, Joshua B. Benoit, Zach N. Adelman, Klaus Reinhardt, Amanda Dolan, Monica Poelchau, Emily C. Jennings, Elise M. Szuter, Richard W. Hagan, Hemant Gujar, Jayendra Nath Shukla, Fang Zhu, M. Mohan, David R. Nelson, Andrew J. Rosendale, Christian Derst, Valentina Resnik, Sebastian Wernig, Pamela Menegazzi, Christian Wegener, Nicolai Peschel, Jacob M. Hendershot, Wolfgang Blenau, Reinhard Predel, Paul R. Johnston, Panagiotis Ioannidis, Robert M. Waterhouse, Ralf Nauen, Corinna Schorn, Mark-Christoph Ott, Frank Maiwald, Subba R. Palli

Entomology Faculty Publications

The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome …

Gascoyne Demersal Scalefish Managed Fishery, Department Of Fisheries

Fisheries Occasional Publications

An operators’ guide to the management arrangements 1 September 2015 – 31 August 2016.

The Emerging Zika Pandemic: Enhancing Preparedness, Lawrence O. Gostin, Daniel Lucey

Georgetown Law Faculty Publications and Other Works

The Zika virus (ZIKV), a flavivirus related to yellow fever, dengue, West Nile, and Japanese encephalitis, originated in the Zika forest in Uganda and was discovered in a rhesus monkey in 1947. The disease now has “explosive” pandemic potential, with outbreaks in Africa, Southeast Asia, the Pacific Islands, and the Americas. Since Brazil reported Zika virus in May 2015, infections have occurred in at least 20 countries in the Americas. Puerto Rico reported the first locally transmitted infection in December 2015, but Zika is likely to spread to the United States. The Aedes species mosquito (an aggressive daytime biter) that …

Antigen Specific Induced T Regulatory Cellular Therapy For Graft-Versus-Host Disease Following Allogeneic Bone Marrow Transplantation, Jessica Lauren Heinrichs

USF Tampa Graduate Theses and Dissertations

Allogeneic hematopoietic stem cell transplantation (allo-HCT) has been a successful cellular therapy for patients suffering from hematological malignancies for many decades; however, the beneficial effects of graft-versus-leukemia (GVL) are classically offset by graft-versus-host disease (GVHD). GVHD occurs when major and/or minor human leukocyte antigen (HLA) mismatches between donor and recipient cause rapid expansion and activation of donor effector T cells (Teffs) resulting in end organ damage to the recipient’s epithelial tissues. Given the lymphoproliferative nature of this disease, the standard treatment option is broad immunosuppression, which can result in primary disease relapse, steroid refractory GVHD, and/or opportunistic infection. A more …

Automated Assessment Of Disease Progression In Acute Myeloid Leukemia By Probabilistic Analysis Of Flow Cytometry Data, Bartek Rajwa, Paul K. Wallace, Elizabeth A. Griffiths, Murat Dundar

Bindley Publications

Objective: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods: The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian …

The Pseudorabies Virus Protein, Pul56, Enhances Virus Dissemination And Virulence But Is Dispensable For Axonal Transport, Gina R. Daniel, Patricia J. Sollars, Gary E. Pickard, Gregory A. Smith

School of Veterinary and Biomedical Sciences: Faculty Publications

Neurotropic herpesviruses exit the peripheral nervous system and return to exposed body surfaces following reactivation from latency. The pUS9 protein is a critical viral effector of the anterograde axonal transport that underlies this process. We recently reported that while pUS9 increases the frequency of sorting of newly assembled pseudorabies virus particles to axons from the neural soma during egress, subsequent axonal transport of individual virus particles occurs with wild-type kinetics in the absence of the protein. Here, we examine the role of a related pseudorabies virus protein, pUL56, during neuronal infection. The findings indicate that pUL56 is a virulence factor …

Local Parasite Lineage Sharing In Temperate Grassland Birds Provides Clues About Potential Origins Of Galapagos Avian Plasmodium, Iris I. Levin, Rachel E. Colborn, Daniel Kim, Noah G. Perlut, Rosalind B. Renfrew, Patricia G. Parker

Environmental Studies Faculty Publications

Oceanic archipelagos are vulnerable to natural introduction of parasites via migratory birds. Our aim was to characterize the geographic origins of two Plasmodium parasite lineages detected in the Galapagos Islands and in North American breeding bobolinks (Dolichonyx oryzivorus) that regularly stop in Galapagos during migration to their South American overwintering sites. We used samples from a grassland breeding bird assemblage in Nebraska, United States, and parasite DNA sequences from the Galapagos Islands, Ecuador, to compare to global data in a DNA sequence registry. Homologous DNA sequences from parasites detected in bobolinks and more sedentary birds (e.g., brown-headed cowbirds …

Local Admixture Of Amplified And Diversified Secreted Pathogenesis Determinants Shapes Mosaic Toxoplasma Gondii Genomes, Hernan Lorenzi, Asis Khan, Michael S. Behnke, Sivaranjani Namasivayam, Lakshmipuram S. Swapna, Michalis Hadjithomas, Svetlana Karamycheva, Deborah Pinney, Brian P. Brunk, James W. Ajioka, Daniel Ajzenberg, John C. Boothroyd, Jon P. Boyle, Marie L. Dardé, Maria A. Diaz-Miranda, Jitender P. Dubey, Heather M. Fritz, Solange M. Gennari, Brian D. Gregory, Kami Kim, Jeroen P. J. Saeij, Chunlei Su, Michael W. White, Xing-Quan Zhu, Daniel K. Howe, Benjamin M. Rosenthal, Michael E. Grigg, John Parkinson, Liang Liu, Jessica C. Kissinger

Veterinary Science Faculty Publications

Toxoplasma gondii is among the most prevalent parasites worldwide, infecting many wild and domestic animals and causing zoonotic infections in humans. T. gondii differs substantially in its broad distribution from closely related parasites that typically have narrow, specialized host ranges. To elucidate the genetic basis for these differences, we compared the genomes of 62 globally distributed T. gondii isolates to several closely related coccidian parasites. Our findings reveal that tandem amplification and diversification of secretory pathogenesis determinants is the primary feature that distinguishes the closely related genomes of these biologically diverse parasites. We further show that the unusual population structure …

Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host-parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we …

Temperature-Dependent Gentamicin Resistance Of Francisella Tularensis Is Mediated By Uptake Modulation, Kathleen Loughman, Jesse Hall, Samantha Knowlton, Chandra S. Bakshi, Joseph Horzempa

NYMC Faculty Publications

Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia - the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.). Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26°C) compared to mammalian body temperature (37°C). To evaluate whether F. tularensis was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those …

Changes In Cytoskeleton Proteins In Hsv-1 Infection Of J774a.1 Macrophage Phenotype, Riham Abbas Subahi

Browse all Theses and Dissertations

The cell cytoskeleton, a unique intracellular matrix found in all eukaryotes, is composed of three main protein structures, microtubules, microlaments and intermediate laments. The cytoskeleton maintains cell shape and internal structures providing mechanical support that facilitates intracellular transport (Parker et al., 2014). Many viruses such as the herpesviruses use the cytoskeleton system of the cell for infectivity (Henry Sum, M. S. 2015). HSV-1 utilizes the cell cytoskeleton in many steps of its life cycle from entry through assembly to egress (Lyman et al., 2008). During infection, HSV-1 viral proteins cause drastic changes and rearrangement of the cellular actin and cell …

Identification And Characterization Of Interactors Of Plasmodium Falciparum Pfpk6, An Atypical Protein Kinase, Andi J. Cummins

Honors Undergraduate Theses

Plasmodium falciparum, the organism that causes the most prevalent and most virulent cases of malaria in humans, poses a major health burden on the developing world, especially in the tropical regions of Sub-Saharan Africa, Southeast Asia, and Latin America. The burden of the disease is intensified by the fact that the parasite has developed widespread resistance to all current antimalarial therapies, such as chloroquine. This drug resistance underscores the need to develop novel therapeutics that target the parasite, but show low toxicity in the human host. Protein kinases, because of their integral roles in cell signaling networks, are considered to …

Identification Of Protein-Protein Interactions Of Amyotrophic Lateral Sclerosis Associated Protein Tdp-43, Hanoor Sharma

Browse all Theses and Dissertations

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by progressive degeneration of upper and lower motor neurons in the brain and spinal cord. Multiple mutations are found in some of the proteins associated with ALS, including superoxide dismutase (SOD1), fused in sarcoma (FUS) and trans-activation response DNA-binding protein (TDP-43). TDP-43 is a DNA and RNA binding protein, well conserved, and ubiquitously expressed in all tissues. TDP-43 resides in the nucleus and sometimes shuttles between nucleus and cytoplasm. Mutations in TDP-43 leads to mislocalization of TDP-43 to the cytosol where it was ubiqutinated and hyperphosphsorylated, ultimately leading to neuronal cell …

Vaccines And Autism: Is There A Link?, Irit Hadi

The Science Journal of the Lander College of Arts and Sciences

There has been a worldwide increase in autism cases in the past few decades, but the cause of it is unclear. It has been suggested that vaccines may be contributing to the rise in autism rates. One claim is that the MMR vaccine can cause intestinal inflammation that may lead non-permeable peptides to be transferred to the brain where it will affect neurodevelopment. This may lead to autism with symptoms of developmental regression and gastrointestinal problems. Another major hypothesis that has received much attention is that a mercury-containing compound, thimerosal, found in many vaccines, can have toxic effects on the …

Aeromonas Hydrophila In Amphibians: Harmless Bystander Or Opportunistic Pathogen, Zachary P. Rivas

Honors Undergraduate Theses

For several decades amphibian populations have been declining. Historically, the bacterium A. hydrophila (Ah) was hypothesized to be the causal factor in amphibian disease and population declines. However, with the discovery of a chytrid fungus, Batrachochytrium dendrobatidis (Bd) in 1998, which was identified on the skin of amphibians during documented mortality events, Ah research became of minor interest as focus shifted to Bd. Recent studies into the immunocompromising abilities of Bd, however, have opened new questions about its relationship with Ah and their combined effects on a host.

In this study, I explore the …