Immunology and Infectious Disease Commons^™

Spread Of Dermacentor Reticulatus Is Associated With The Loss Of Forest Area, Ewa J. Mierzejewska, Agustín Estrada-Peña, Anna Bajer

Harold W. Manter Laboratory of Parasitology: Library Materials

Changes in tick distribution and abundance are among the main drivers of the (re)emergence of transmitted pathogens. We aimed to uncover the reasons of the reported spread of Dermacentor reticulatus in Poland using a variety of proxies of environmental features, ground-measured temperature and remotely-sensed data of temperature and vegetation. Ground-measured temperature was recorded in 2013–2014, in sites where D. reticulatus presence (n = 16) or absence (n = 16) was confirmed. We specifically aimed to test whether changes in phenology of vegetation and the length of the growing season were correlated with field-derived data regarding the presence/absence of D. reticulatus …

Redirection Of The Immune Response To Staphylococcus Aureus Biofilm Infection, Anna G. Staudacher

Theses & Dissertations

Staphylococcus aureus (S. aureus) is a leading cause of community- and healthcare-associated infections and has a propensity to form biofilms. Biofilm infections are recalcitrant to host immune-mediated clearance as well as antibiotics, making them exceptionally difficult to eradicate. The biofilm environment has been shown to skew the host immune response towards an anti-inflammatory phenotype, characterized by alternatively activated macrophages, recruitment of myeloid-derived suppressor cells (MDSCs), and minimal neutrophil and T cell infiltrates. Our laboratory has attempted to redirect the host immune response towards one that would favor bacterial clearance by employing strategies to augment pro-inflammatory mechanisms. One such …

Development Of C5ar-Targeted Nanoparticles For Delivery Of Vaccines, Shailendra Bharadwaj Tallapaka Venkata Sesha

Theses & Dissertations

Since the early attempts of Benjamin Jesty at inducing immunity against smallpox and the pioneering work of Edward Jenner, vaccination has been, and continues to remain, the principal method of protection from diseases. However, most of the successful vaccines have been against pathogens that do not have major mechanisms to evade the immune system. So far, many life-threatening diseases like hepatitis C, HIV infection, malaria etc., have been resistant to existing vaccination strategies. Thus, there is an urgent need to develop new vaccination strategies that can generate long-lived protective immunity against such pathogens.

The purpose of this thesis is to …

More Haste, Less Speed: Could Public-Private Partnerships Advance Cellular Immunotherapies?, Tania M. Bubela, Katherine Bonter, Silvy Lachance, Jean-Sébastien Delisle, E Richard Gol

Office of the Provost

Cellular immunotherapies promise to transform cancer care. However, they must overcome serious challenges, including: (1) the need to identify and characterize novel cancer antigens to expand the range of therapeutic targets; (2) the need to develop strategies to minimize serious adverse events, such as cytokine release syndrome and treatment-related toxicities; and (3) the need to develop efficient production/manufacturing processes to reduce costs. Here, we discuss whether these challenges might better be addressed through forms of public-private research collaborations, including public-private partnerships (PPPs), or whether these challenges are best addressed by way of standard market transactions. We reviewed 14 public-private relationships …

Robust Odorant Recognition In Biological And Artificial Olfaction, Nalin Katta

McKelvey School of Engineering Graduate Student Theses & Dissertations

Accurate detection and identification of gases pose a number of challenges for chemical sensory systems. The stimulus space is enormous; volatile compounds vary in size, charge, functional groups, and isomerization among others. Furthermore, variability arises from intrinsic (poisoning of the sensors or degradation due to aging) and extrinsic (environmental: humidity, temperature, flow patterns) sources. Nonetheless, biological olfactory systems have been refined over time to overcome these challenges. The main objective of this work is to understand how the biological olfactory system deals with these challenges, and translate them to artificial olfaction to achieve comparable capabilities. In particular, this thesis focuses …

Cross-Species Transmission Potential Between Wild Pigs, Livestock, Poultry, Wildlife, And Humans: Implications For Disease Risk Management In North America, Ryan S. Miller, Steven Sweeney, Chris Slootmaker, Daniel A. Grear, Paul A. Di Salvo, Deborah Kiser, Stephanie A. Shwiff

Zoonotics and Wildlife Disease: Publications

Cross-species disease transmission between wildlife, domestic animals and humans is an increasing threat to public and veterinary health. Wild pigs are increasingly a potential veterinary and public health threat. Here we investigate 84 pathogens and the host species most at risk for transmission with wild pigs using a network approach. We assess the risk to agricultural and human health by evaluating the status of these pathogens and the co-occurrence of wild pigs, agriculture and humans. We identified 34 (87%) OIE listed swine pathogens that cause clinical disease in livestock, poultry, wildlife, and humans. On average 73% of bacterial, 39% of …

Secreted Ns1 Aids In Dengue Virus Entry By Binding Heparan Sulfate, Morgan E. Schafer, Michael Dibiasio-White, Richard J. Kuhn

The Summer Undergraduate Research Fellowship (SURF) Symposium

A large portion of the world’s population lives in an area where they are at risk of contracting Dengue Virus (DENV). While infection with DENV can result in a wide range of clinical manifestations, from flu-like symptoms to hemorrhagic shock, vascular leakage, and even death, no treatments currently exist. Previous studies have shown that higher levels of viral non-structural protein 1 (NS1) in the blood of infected patients correlate with more severe disease. NS1 has been shown to play many roles in the viral lifecycle, but the mechanisms by which NS1 executes these functions are unknown. Preliminary data from our …

Computational Drug Design: A Multitargeted Approach In Bladder Cancer, Travis C. Lantz, Joydeb Majumder, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer is a complex, robust disease with multiple redundant disease pathways which lead to tumor development, growth, and eventually even death. Despite known redundancies, cancer therapeutics continue to be developed against a single protein target. Initial disease regression occurs followed by relapse in a drug resistant disease state. In response, combinational drug clinical trial targeting multiple pathways began, and have failed due to increased toxicity caused by adverse drug interactions. Development of a single drug that differentially targets multiple disease pathways will result in a more potent therapeutic while inducing minimal toxicity. This was done computationally through in-lab software packages, …

Taxonomy And Systematics Of Plagioporus (Trematoda), With Descriptions Of 10 New Species From Freshwater Fishes Of The Nearctic, Thomas John Fayton

Dissertations

The Opecoelidae Ozaki, 1925 is one of the largest families of digenetic trematodes of fishes. While the family is mostly marine/estuarine, invasion of freshwater hosts has occurred at least two times. The only representative freshwater plagioporine sequenced to date is Plagiocirrus loboides Curran, Overstreet, & Tkach, 2007, which previous phylogenetic analyses resolved as being related to deep water marine opecoelids. The taxonomy of the freshwater plagioporines, particularly Plagioporus, has long been confused; homoplasy is rife within the family and has complicated the delineation of species and genera, and the freshwater species from marine forms. Here, I hypothesize that the …

Characterization Of Filifactor Alocis And Its Immune Evasion Strategies Employed Against Human Neutrophils., Cortney Linn Armstrong

Electronic Theses and Dissertations

Periodontal disease is among the most common of inflammatory conditions and is caused by bacterial and host derived factors. The presence of bacteria drives the recruitment of neutrophils, professional phagocytes, to migrate to specific oral sites where they produce potent antimicrobials to kill their target. However, this inflammation and production of antimicrobials must be strictly regulated to minimize collateral host tissue damage. Human neutrophils recognized the oral pathogen Filifactor alocis through Toll-like receptor (TLR) 2 and upon binding, activated both p38 MAPK and ERK signaling pathways, known to be involved in neutrophil cell migration and degranulation. F. alocis also stimulated …

Peptide Inhibitors Targeting The Neisseria Gonorrhoeae Pivotal Anaerobic Respiration Factor Ania, Aleksandra E. Sikora, Robert H. Mills, Jacob V. Weber, Adel Hamza, Bryan W. Passow, Andrew Romaine, Zachary A. Williamson, Robert W. Reed, Ryszard A. Zielke, Konstantin V. Korotkov

Molecular and Cellular Biochemistry Faculty Publications

Neisseria gonorrhoeae causes the sexually transmitted infection gonorrhea, which is highly prevalent worldwide and has a major impact on reproductive and neonatal health. The superbug status of N. gonorrhoeae necessitates the development of drugs with different mechanisms of action. Here, we focused on targeting the nitrite reductase AniA, which is a pivotal component of N. gonorrhoeae anaerobic respiration and biofilm formation. Our studies showed that gonococci expressing AniA containing the altered catalytic residues D137A and H280A failed to grow under anaerobic conditions, demonstrating that the nitrite reductase function is essential. To facilitate the pharmacological targeting of AniA, new crystal structures …

Targeting Fas Pathway As An Effective Means Of Inducing Tolerance To Pancreatic Islets., Kyle Blake Woodward

Electronic Theses and Dissertations

Signaling through Fas/FasL is critical to immune homeostasis and tolerance to self-antigens. SA-FasL is a chimeric protein of FasL and streptavidin. SA-FasL exists as oligomers with potent apoptotic function on Fas expressing immune cells and tightly binds to biotinylated surfaces. Islet grafts engineered to transiently display SA-FasL on their surface established tolerance in allogeneic recipients with a short course of rapamycin. We hypothesized that SA-FasL on the islet allograft will induce apoptosis in alloreactive T effector (Teff) cells and phagocytes clearing apoptotic bodies will produce tolerogenic molecules, such as TGF-β, that will lead to the generation and/or expansion of Treg …

A Parapoxviral Virion Protein Inhibits Nf-Κb Signaling Early In Infection, Sushil Khatiwada, Gustavo A. Delhon, Ponnuraj Nagendraprabhu, Sabal Chaulagain, Shuhong Luo, Diego G. Diel, Eduardo F. Flores, D. L. Rock

School of Veterinary and Biomedical Sciences: Faculty Publications

Poxviruses have evolved unique proteins and mechanisms to counteract the nuclear factor κB (NF-κB) signaling pathway, which is an essential regulatory pathway of host innate immune responses. Here, we describe a NF-κB inhibitory virion protein of orf virus (ORFV), ORFV073, which functions very early in infected cells. Infection with ORFV073 gene deletion virus (OV-IA82Δ073) led to increased accumulation of NF-κB essential modulator (NEMO), marked phosphorylation of IκB kinase (IKK) subunits IKKα and IKKβ, IκBα and NF-κB subunit p65 (NF-κB-p65), and to early nuclear translocation of NF-κB-p65 in virusinfected cells (30 min post infection). Expression of ORFV073 alone was sufficient to …

Knowledge And Perceptions About Zika Virus In A Middle East Country, Sohaila Cheema, Patrick Maisonneuve, Ingmar Weber, Luis Fernandez-Luque, Amit Abraham, Albert B. Lowenfels, Ravinder Mamtani

NYMC Faculty Publications

BACKGROUND: Zika virus, an emerging serious infectious disease, is a threat to persons living or travelling to regions where it is currently endemic, and also to contacts of infected individuals. The aim of this study was to assess knowledge about this new public health threat to persons residing in a Middle Eastern country.

METHODS: We conducted a survey at several international universities in Qatar to assess knowledge and awareness about this disease. An adapted version of the survey was also conducted using online channels from Qatar.

RESULTS: The median age of the 446 participants, was 25 years, 280 (63%) were …

Checklist Of Helminths Of Bats From Mexico And Central America, F. Agustín Jiménez, Juan M. Caspeta-Mandujano, Said B. Ramírez-Chávez, Silvia E. Ramírez-Díaz, Marissa G. Juárez-Urbina, Jorge L. Peralta-Rodríguez, José A. Guerrero

MANTER: Journal of Parasite Biodiversity

Based on original data obtained from fieldwork conducted from January 2008 to December 2015 and from previous records from published accounts, an updated checklist of helminth parasites of bats from Mexico and Central America is presented. The checklist has been organized in four ways, first as a helminth-host list in the state of Morelos, second as a helminth-host list with taxonomic and geographic distributional information, third as a bat-helminth list with references, and last, as a summary of the host-helminth association. A total of 105 records and 67 helminth taxa (26 trematodes, 4 cestodes, and 37 nematodes [33 adult and …

Changes In The Gut Microbial Communities Following Addition Of Walnuts To The Diet, Lauri O. Byerley, Derrick Samuelson, Eugene Blanchard, Meng Luo, Brittany N. Lorenzen, Shelia Banks, Monica A. Ponder, David A. Welsh, Christopher M. Taylor

School of Graduate Studies Faculty Publications

Walnuts are rich in omega-3 fatty acids, phytochemicals and antioxidants making them unique compared to other foods. Consuming walnuts has been associated with health benefits including a reduced risk of heart disease and cancer. Dysbiosis of the gut microbiome has been linked to several chronic diseases. One potential mechanism by which walnuts may exert their health benefit is through modifying the gut microbiome. This study identified the changes in the gut microbial communities that occur following the inclusion of walnuts in the diet. Male Fischer 344 rats (n=20) were randomly assigned to one of two diets for as long as …

Rational Drug Design Directed At Blocking The Initial Signaling Events In Lipopolysaccharide-Induced Sepsis., Christopher A. Tipton

Theses

Systemic Inflammatory Response Syndrome (SIRS) is classified as an immune system response to an infectious state. If left untreated, SIRS leads to sepsis, septic shock, end-organ dysfunction, and death. As a patient progresses through these stages, associations of acute respiratory distress, disseminated intravascular coagulation, and acute renal failure persist, resulting in millions of deaths annually. Lipopolysaccharide (LPS), a bacterial endotoxin, is released into the blood stream, triggering SIRS. LPS is found in the outer cell-wall of Gram-negative bacteria and is responsible for initiation of a devastating cytokine storm. One of the regions of LPS, lipid A, is a polyacylated glucosamine …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …

Ectoparasitic Mites Of The Genus Gigantolaelaps (Acari: Mesostigmata: Laelapidae) Associated With Small Mammals Of The Genus Nephelomys (Rodentia: Sigmodontinae), Including Two New Species From Peru, Donald D. Gettinger, Scott Lyell Gardner

Scott L. Gardner Publications

An extensive survey of small mammals and ectoparasites along an altitudinal transect in the Manu Biodiversity Reserve in Peru found the sigmodontine rodent genus Nephelomys infested by mites of the genus Gigantolaelaps Fonseca, 1939. Two distinct species co-occurred exclusively in the pelage of Nephelomys keaysi, G. inca Fonseca and G. minima n. sp. Nephelomys levipes, which replaces N. keaysi at higher elevations, was infested exclusively with a single new species, G. nebulosa n. sp. In this paper, we formally describe these new mite species, and provide more information on the morphology of G. inca.

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous …