Immunology and Infectious Disease Commons^™

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 …

Evolution Of Bat-Trypanosome Associations And The Origins Of Chagas Disease, Christian Miguel Pinto

Dissertations, Theses, and Capstone Projects

Trypanosoma cruzi is a genetically diverse parasite that causes Chagas disease, one of the most important zoonoses in the Americas. This generalist parasite of mammals belongs to a clade mostly comprised of bat parasites, the T. cruzi clade. The origins (i.e., biogeographic history and evolution of hosts associations) of this parasite are far from being understood, and the main areas that need further study are: species limits within T. cruzi sensu lato, further studies on the diversity of T. cruzi clade members and their hosts, and research on adaptations of the hosts to trypanosome infections. In this dissertation I explore …

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 …

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 …

Dynamically-Expressed Prion-Like Proteins Form A Cuticle In The Pharynx Of Caenorhabditis Elegans, Julia B. George-Raizen, Keith R. Shockley, Nicholas F. Trojanowski, Annesia L. Lamb, David M. Raizen

Publications and Research

In molting animals, a cuticular extracellular matrix forms the first barrier to infection and other environmental insults. In the nematode Caenorhabditis elegans there are two types of cuticle: a wellstudied collagenous cuticle lines the body, and a poorly-understood chitinous cuticle lines the pharynx. In the posterior end of the pharynx is the grinder, a tooth-like cuticular specialization that crushes food prior to transport to the intestine for digestion. We here show that the grinder increases in size only during the molt. To gain molecular insight into the structure of the grinder and pharyngeal cuticle, we performed a microarray analysis to …

Environmental Data Analysis And Remote Sensing For Early Detection Of Dengue And Malaria, Md Zahidur Rahman, Leonid Roytman, Abdelhamid Kadik, Dilara A. Rosy

Publications and Research

Malaria and dengue fever are the two most common mosquito-transmitted diseases, leading to millions of serious illnesses and deaths each year. Because the mosquito vectors are sensitive to environmental conditions such as temperature, precipitation, and humidity, it is possible to map areas currently or imminently at high risk for disease outbreaks using satellite remote sensing. In this paper we propose the development of an operational geospatial system for malaria and dengue fever early warning; this can be done by bringing together geographic information system (GIS) tools, artificial neural networks (ANN) for efficient pattern recognition, the best available ground-based epidemiological and …

Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley

Publications and Research

Background. Genital tract (GT) inflammation plays a major role in HIV transmission. We aimed to determine the association between symptomatic vulvovaginal candidiasis (VVC) and HIV RNA levels in plasma and GTs of HIV-infected women on highly active antiretroviral therapy (HAART).

Method. Women with VVC on HAART were recruited from a primary healthcare clinic in KwaZulu-Natal Province, South Africa, between June 2011 and December 2011. VVC was diagnosed clinically, supported by Gram staining and culture of genital secretions. HIV RNA load was determined by reverse transcription polymerase chain reaction. CD4+ counts were obtained from patients’ medical records.

Results. Plasma HIV RNA …

Epidemiology Of Undiagnosed Trichomoniasis In A Probability Sample Of Urban Young Adults, Susan M. Rogers, Charles F. Turner, Marcia Hobbs, William C. Miller, Sylvia Tan, Anthony M. Roman, Elizabeth Eggleston, Maria A. Villarroel, Laxminarayana Ganapathi, James R. Chromy, Emily Erbelding

Publications and Research

T. vaginalis infection (trichomoniasis) is the most common curable sexually transmitted infection (STI) in the U.S. It is associated with increased HIV risk and adverse pregnancy outcomes. Trichomoniasis surveillance data do not exist for either national or local populations. The Monitoring STIs Survey Program (MSSP) collected survey data and specimens which were tested using nucleic acid amplification tests to monitor trichomoniasis and other STIs in 2006–09 among a probability sample of young adults (N = 2,936) in Baltimore, Maryland — an urban area with high rates of reported STIs. The estimated prevalence of trichomoniasis was 7.5% (95% CI 6.3, 9.1) …

Chagas Disease In The 21st Century: A Public Health Success Or An Emerging Threat?, Kevin M. Bonney

Publications and Research

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major public health burden in Latin America and a potentially serious emerging threat to a number of countries throughout the world. Although public health programs have significantly reduced the prevalence of Chagas disease in Latin America in recent decades, the number of infections in the United States and non-endemic countries in Europe and the Western Pacific Region continues to rise. Moreover, there is still no vaccine or highly effective cure available for the approximately 10 million people currently infected with T. cruzi, a third of which will develop potentially …

Roles Of Igh Intronic Enhancer Eμ In Clonal Selection At The Pre-B To Immature B Cell Transition And In The Elimination Of Autoreactive B Cells, Cheng Peng

Dissertations, Theses, and Capstone Projects

The immunoglobulin heavy chain locus (Igh ) intronic enhancer, Eμ, enhances transcription of recombined Igh genes. We have previously shown that in mice with an Eμ-deficient Igh allele (V _H δ^a ), Igμ is expressed at half of the wild-type levels in pre-B cells. We also described an Eμ-dependent "check-point", operating at the pre-B to immature B cell transition, for heavy chain allelic exclusion. We now show that deletion of Eμ results in a smaller immature B cell compartment, and the pre-BCR/BCR signaling is diminished in pre-B cells as a result of the reduced Igμ levels, making it …

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

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

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, …

Structure-Function Analysis Of Zapc, An Ftsz-Ring Stabilizer, In Escherichia Coli Cytokinesis, Lukasz Tchorzewski

Dissertations and Theses

In Escherichia coli, cell division is defined by the polymerization and constriction of a cytokinetic ring (Z ring) formed by FtsZ, a tubulin-like GTPase, at midcell. Division also involves the formation of a multi-protein complex at midcell known as the divisome. Several divisome proteins promote the assembly/disassembly processes of FtsZ, thereby exercising spatiotemporal control over division. Among FtsZ regulatory proteins are the FtsZ ringassociated proteins (Zap), which either directly or indirectly stabilize the Z-ring by increasing lateral interactions amongst FtsZ protofilaments in the Z-ring. ZapA-D are recruited during early cytokinesis and have overlapping functions in stabilizing FtsZ at midcell, but …

Changes In Natural Killer Cell Activation And Function During Primary Hiv-1 Infection, Vivek Naranbhai, Marcus Altfeld, Salim S. Abdool Karim, Thumbi Ndung’U, Quarraisha Abdool Karim, William H. Carr

Publications and Research

Background: Recent reports suggest that Natural Killer (NK) cells may modulate pathogenesis of primary HIV-1 infection. However, HIV dysregulates NK-cell responses. We dissected this bi-directional relationship to understand how HIV impacts NK-cell responses during primary HIV-1 infection.

Methodology/Principal Findings: Paired samples from 41 high-risk, initially HIV-uninfected CAPRISA004 participants were analysed prior to HIV acquisition, and during viraemic primary HIV-1 infection. At the time of sampling post-infection five women were seronegative, 11 women were serodiscordant, and 25 women were seropositive by HIV-1 rapid immunoassay. Flow cytometry was used to measure NK and T-cell activation, NK-cell receptor expression, cytotoxic and cytokine-secretory functions, …

Polyglutamine Toxicity Is Controlled By Prion Composition And Gene Dosage In Yeast, He Gong, Nina V. Romanova, Kim D. Allen, Pavithra Chandramowlishwaran, Kavita Gokhale, Gary P. Newnam, Piotr Miceczkowski, Michael Y. Sherman, Yury O. Chernoff

Publications and Research

Polyglutamine expansion causes diseases in humans and other mammals. One example is Huntington’s disease. Fragments of human huntingtin protein having an expanded polyglutamine stretch form aggregates and cause cytotoxicity in yeast cells bearing endogenous QN-rich proteins in the aggregated (prion) form. Attachment of the proline(P)-rich region targets polyglutamines to the large perinuclear deposit (aggresome). Aggresome formation ameliorates polyglutamine cytotoxicity in cells containing only the prion form of Rnq1 protein. Here we show that expanded polyglutamines both with (poly-QP) or without (poly-Q) a P-rich stretch remain toxic in the presence of the prion form of translation termination (release) factor Sup35 (eRF3). …

Parasites Of Civets (Mammalia, Viverridae) In Sabah, Borneo: A Coprological Survey, Christina P. Colon, Sharon Patton

Publications and Research

Parasite data were collected from unlogged and selectively logged lowland rain forests in Borneo. Scat from a female Viverra tangalunga (Malay civet) in the unlogged forest contained eggs of Capillaria spp., Trichuris sp., Mamomoganomus sp., and nematode larvae. Scat attributed to V. tangalunga contained reproductive products (eggs/oocysts/cysts/larvae) of Capillaria sp., Toxocara sp., Ancylostoma sp. (probably A. ceylanicum), Isospora spp., strongylate-type eggs (probably Ancylostoma spp.), Paragoni­ mus sp. and other Trematoda eggs, Monocystis sp. cysts, Gnathostoma sp. (probably G. spinigerum), the lungworm Viverrostrongylus brauni, pinworm-type eggs, Eimeria spp., Sarcocystis-type sporocyst, dermanysid mites and mesostigmatid mites. Parasites from gut samples from two …

Study Guide For United In Anger: A History Of Act Up, Matt Brim

Open Educational Resources

The United in Anger Study Guide facilitates classroom and activist engagement with Jim Hubbard’s 2012 documentary, United in Anger: A History of ACT UP. The Study Guide contains discussion sections, projects and exercises, and resources for further research about the activism of the New York chapter of ACT UP (AIDS Coalition to Unleash Power). The Study Guide is a free, interactive, multimedia resource for understanding the legacy of ACT UP, the film’s role in preserving that legacy, and its meaning for viewers' lives.

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 …

Role For Sumoylation In Systemic Inflammation And Immune Homeostasis In Drosophila Larvae, Indira Paddibhatla, Mark J. Lee, Marta E. Kalamarz, Roberto Ferrarese, Shubha Govind

Publications and Research

To counter systemic risk of infection by parasitic wasps, Drosophila larvae activate humoral immunity in the fat body and mount a robust cellular response resulting in encapsulation of the wasp egg. Innate immune reactions are tightly regulated and are resolved within hours. To understand the mechanisms underlying activation and resolution of the egg encapsulation response and examine if failure of the latter develops into systemic inflammatory disease, we correlated parasitic wasp-induced changes in the Drosophila larva with systemic chronic conditions in sumoylation-deficient mutants. We have previously reported that loss of either Cactus, the Drosophila (IkB) protein or Ubc9, the SUMO-conjugating …

Contrasting Infection Strategies In Generalist And Specialist Wasp Parasitoids Of Drosophila Melanogaster, Todd A. Schlenke, Jorge Morales, Shubha Govind, Andrew G. Clark

Publications and Research

Although host–parasitoid interactions are becoming well characterized at the organismal and cellular levels, much remains to be understood of the molecular bases for the host immune response and the parasitoids’ ability to defeat this immune response. Leptopilina boulardi and L. heterotoma, two closely related, highly infectious natural parasitoids of Drosophila melanogaster, appear to use very different infection strategies at the cellular level. Here, we further characterize cellular level differences in the infection characteristics of these two wasp species using newly derived, virulent inbred strains, and then use whole genome microarrays to compare the transcriptional response of Drosophila to each. While …

Bioorganic Studies In Aids: Synthetic Antifungals Against Pneumocystis Carinii Based On The Multivalency Concept, Langu Peng, Cunxiang Chen, Christian R. Gonzalez, Valeria Balogh-Nair

Publications and Research

We report the syntheses of antifungals containing the novel pharmacophores: oxaziridines, sulfonyloxaziridines, nitrones and nitronyl nitroxides. We hypothesized that multiple copies of the pharmacophore per molecule might be a prerequisite to enhance efficacy against the opportunistic pathogen, Pneumocystis carinii. Therefore structural optimization of the leads was based on this new “multivalency” approach. All bisoxaziridines were inactive, but a trisoxaziridine caused ca. 50% reduction of the number of P. carinii tropozoites, compared to TMP-SMX, and a hexaoxaziridine at 1 µg/ml showed activity comparable to the currently used drug, TMP-SMX. Insertion of three units of the nitronyl nitroxide pharmacophore per molecule afforded …