Digital Commons Network^™

Microfluidic Platform For Electrophysiological Recordings From Host-Stage Hookworm And Ascaris Suum Larvae: A New Tool For Anthelmintic Research, Janis Weeks, William Roberts, Kristin Robinson, Melissa Keaney, Jon Vermiere, Joseph Urban, Shawn Lockery, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The screening of candidate compounds and natural products for anthelmintic activity is important for discovering new drugs against human and animal parasites. We previously validated in Caenorhabditis elegans a microfluidic device (‘chip’) that records non-invasively the tiny electrophysiological signals generated by rhythmic contraction (pumping) of the worm's pharynx. These electropharyngeograms (EPGs) are recorded simultaneously from multiple worms per chip, providing a medium-throughput readout of muscular and neural activity that is especially useful for compounds targeting neurotransmitter receptors and ion channels. Microfluidic technologies have transformedC. elegans research and the goal of the current study was to validate hookworm andAscaris …

Experimental Infection Of Conventional Nursing Pigs And Their Dams With Porcine Deltacoronavirus, Sarah Vitosh-Sillman, John Dustin Loy, Bruce W. Brodersen, Clayton L. Kelling, Alan R. Doster, Christina L. Topliff, Eric A. Nelson, Jianfa Bai, Erin Schirtzinger, Elizabeth Poulsen, Barbara Meadors, Joseph Anderson, Benjamin Hause, Gary Anderson, Richard Hesse

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine deltacoronavirus (PDCoV) is a newly identified virus that has been detected in swine herds of North America associated with enteric disease. The aim of this study was to demonstrate the pathogenicity, course of infection, virus kinetics, and aerosol transmission of PDCoV using 87 conventional piglets and their 9 dams, including aerosol and contact controls to emulate field conditions. Piglets 2–4 days of age and their dams were administered an oronasal PDCoV inoculum with a quantitative real-time reverse transcription (qRT)-PCR quantification cycle (Cq) value of 22 that was generated from a field sample having 100% nucleotide identity to USA/Illinois121/2014 determined …

Changing Diagnostic Methods And Increased Detection Of Verotoxigenic Escherichia Coli, Ireland, Thomas Rice, Noreen Quinn, Roy D. Sleator, Brigid Lucey

Department of Biological Sciences Publications

The recent paradigm shift in infectious disease diagnosis from culture-based to molecular-based approaches is exemplified in the findings of a national study assessing the detection of verotoxigenic Escherichia coli infections in Ireland. The methodologic changes have been accompanied by a dramatic increase in detections of non-O157 verotoxigenic E. coli serotypes.

Requirements For Pseudomonas Aeruginosa Type I-F Crispr-Cas Adaptation Determined Using A Biofilm Enrichment Assay, Gary E. Heussler, Jon L. Miller, Courtney E. Price, Alan J. Collins

Dartmouth Scholarship

CRISPR (clustered regularly interspaced short palindromic repeat)-Cas (CRISPR-associated protein) systems are diverse and found in many archaea and bacteria. These systems have mainly been characterized as adaptive immune systems able to protect against invading mobile genetic elements, including viruses. The first step in this protection is acquisition of spacer sequences from the invader DNA and incorporation of those sequences into the CRISPR array, termed CRISPR adaptation. Progress in understanding the mechanisms and requirements of CRISPR adaptation has largely been accomplished using overexpression of cas genes or plasmid loss assays; little work has focused on endogenous CRISPR-acquired immunity from viral predation. …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

Polycations. 23. Antimicrobial Surfaces For Prevention Of Pathogen Transmission, Robert Engel, Karin Melkonian, Jay Ho, Jaime Lee Iolani Rizzo

Publications and Research

The continued evolution of bacterial and fungal species poses a significant difficulty for the treatment of disease of microbial origin. Given this situation, the prevention of transmission of such microbial diseases becomes of increasing importance. Efforts of this laboratory have been directed toward the destruction of microbial species on environmental surfaces as a prophylaxis toward infection, and we herein report on the efficacy of a system that demonstrates activity against both Gram-positive and Gram-negative bacteria, as well as fungi. We report specifically herein on the use of fabric materials so activated for the destruction of these microbial species, useful for …

Ehd1 As A Positive Regulator Of Macrophage Colony-Stimulating Factor-1 Receptor, Luke R. Cypher

Theses & Dissertations

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream …

Week Of August 8, 2016, New York Medical College

InTouch

• NYMC Welcomes SOM Class of 2020
• Andrew Mutnick, M.D. '01, Is Named SOM Associate Dean for Student Affairs
• SOM Office of Admissions Seeks MMI Interviewers
• SOM Offers High School Students Hands-On Look at Medicine

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

Multipronged Approach To Study Glaucoma-Associated Phenotypes, Sumana Rameshbabu Chintalapudi

Theses and Dissertations (ETD)

Glaucoma refers to a group of conditions characterized by death of RGCs, increase in intraocular pressure is usually a precursor to glaucoma and irreversible optic neuropathy leads to visual impairment and blindness. Recent advances have seen a surge of new ideas and technologies to aid in the early detection, efficacious treatments and neuroprotection. Despite advances we face several challenges in understanding the pathophysiology of glaucoma. One of the many challenges scientists and ophthalmologists are facing is, to better understand IOP, its role in glaucomatous damage and design safer, more predictable IOP-lowering therapies. Another challenge is to find a practical method …

Hepatic Fibrosis And Immune Phenotype Vary By Hcv Viremia In Hcv/Hiv Co-Infected Subjects: A Women's Interagency Hiv Study., Seema N Desai, Jennifer L Dodge, Alan L Landay, Marshall J Glesby, Patricia S. Latham, Maria C Villacres, Audrey L French, Stephen J Gange, Ruth M Greenblatt, Marion G Peters

Pathology Faculty Publications

HCV and HIV independently lead to immune dysregulation. The mechanisms leading to advanced liver disease progression in HCV/HIV coinfected subjects remain unclear.

In this cross-sectional study, we assessed the association of HCV viremia, liver fibrosis, and immune response patterns in well-characterized HIV phenotypes: Elite controllers (Elites), HIV controlled (ARTc), and HIV uncontrolled (ARTuc) matched by age and race. Groups were stratified by HCV RNA status. Regulatory T-cell frequencies, T-cell activation (HLADR+CD38+), apoptosis (Caspase-3+), and intracellular cytokines (interferon-γ, IL-2, IL-17) were assessed using multiparametric flow-cytometry. Liver fibrosis was scored by AST to platelet ratio index (APRI).

We found liver fibrosis (APRI) …

The Roles Of Nuclear Receptor Nr4a1 In Cancer Cell Proliferation And Skeletal Muscle Differentiation, Alexa Farmer

Theses and Dissertations (ETD)

Nuclear receptors (NRs) constitute a major class of drug targets in the treatment of various cancer types. NRs respond to cellular signals and become activated upon ligand binding to transcriptionally modulate expression of target genes. NR4A1 (Nur77) is a member of the NR4A family of nuclear receptors and displays an oncogenic profile in many cancer models. It is often upregulated in adult solid malignancies and is known to promote cell proliferation and survival. Knockdown studies of NR4A1 in cancer cell lines results in decreased cell growth and angiogenesis and increased apoptosis, suggesting NR4A1 is an oncogenic protein. Due to the …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5-fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. Ad5-R3 …

Effects Of Tcpb Mutations On Biogenesis And Function Of The Toxin-Coregulated Pilus, The Type Ivb Pilus Of Vibrio Cholerae, Yang Gao, Caitlyn A. Hauke, Jarrad M. Marles, Ronald K. Taylor

Dartmouth Scholarship

Vibrio cholerae is the etiological agent of the acute intestinal disorder cholera. The toxin-coregulated pilus (TCP), a type IVb pilus, is an essential virulence factor of V. cholerae. Recent work has shown TcpB is a large minor pilin encoded within the tcp operon. TcpB contributes to efficient pilus formation and is essential for all TCP functions. Here we have initiated a detailed, targeted mutagenesis approach to further characterize this salient TCP component. We have identified (thus far) 20 residues of TcpB, which affect either the steady state level of TcpB or alter one or more TCP functions. This study …

Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated By Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I, Seung Bum Park, Scott Seronello, Wasima Mayer, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Hepatitis C virus (HCV) actively evades host interferon (IFN) responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I)-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP) from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP) and poly(IC). The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in …

Biliary Microbiota, Gallstone Disease And Infection With Opisthorchis Felineus., Irina V. Saltykova, Vjacheslav A Petrov, Maria D Logacheva, Polina G Ivanova, Nikolay V Merzlikin, Alexey E Sazonov, Ludmila M Ogorodova, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.

METHODOLOGY/PRINCIPAL FINDINGS: Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from …

Cyclic Di-Gmp-Regulated Periplasmic Proteolysis Of A Pseudomonas Aeruginosa Type Vb Secretion System Substrate, Richard B. Cooley, T. Jarrod Smith, Wilfred Leung, Valerie Tierney, Bradley Borlee, George A. O'Toole, Holger Sondermann

Dartmouth Scholarship

We previously identified a second-messenger-regulated signaling system in the environmental bacterium Pseudomonas fluorescens which controls biofilm formation in response to levels of environmental inorganic phosphate. This system contains the transmembrane cyclic di-GMP (c-di-GMP) receptor LapD and the periplasmic protease LapG. LapD regulates LapG and controls the ability of this protease to process a large cell surface adhesin protein, LapA. While LapDG orthologs can be identified in diverse

Week Of June 20, 2016, New York Medical College

InTouch

• Victor T. Madubuko Is Named Diversity and Inclusion Officer
• Department of Family and Community Medicine Hosts Annual Faculty Appreciation Dinner
• NYMC Honors Preceptors and Seminar Leaders at Annual Dinner
• School of Medicine Joins Ranks of AAMC Te4Q Sites

The Pseudomonas Aeruginosa Efflux Pump Mexghi-Opmd Transports A Natural Phenazine That Controls Gene Expression And Biofilm Development, Hassan Sakhtah, Leslie Koyama, Yihan Zhang, Diana K. Morales, Blanche Fields, Alexa Price-Whelan, Deborah Hogan

Dartmouth Scholarship

Redox-cycling compounds, including endogenously produced phenazine antibiotics, induce expression of the efflux pump MexGHI-OpmD in the opportunistic pathogen Pseudomonas aeruginosa Previous studies of P. aeruginosa virulence, physiology, and biofilm development have focused on the blue phenazine pyocyanin and the yellow phenazine-1-carboxylic acid (PCA). In P. aeruginosa phenazine biosynthesis, conversion of PCA to pyocyanin is presumed to proceed through the intermediate 5-methylphenazine-1-carboxylate (5-Me-PCA), a reactive compound that has eluded detection in most laboratory samples. Here, we apply electrochemical methods to directly detect 5-Me-PCA and find that it is transported by MexGHI-OpmD in P. aeruginosa strain PA14 planktonic and biofilm cells. We …

Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …

Membrane Insertion For The Detection Of Lipopolysaccharides: Exploring The Dynamics Of Amphiphile-In-Lipid Assays, Loreen R. Stromberg, Nicolas W. Hengartner, Kirstie L. Swingle, Rodney A. Moxley, Steven W. Graves, Gabriel A. Montaño, Harshini Mukundan

School of Veterinary and Biomedical Sciences: Faculty Publications

Shiga toxin-producing Escherichia coli is an important cause of foodborne illness, with cases attributable to beef, fresh produce and other sources. Many serotypes of the pathogen cause disease, and differentiating one serotype from another requires specific identification of the O antigen located on the lipopolysaccharide (LPS) molecule. The amphiphilic structure of LPS poses a challenge when using classical detection methods, which do not take into account its lipoglycan biochemistry. Typically, detection of LPS requires heat or chemical treatment of samples and relies on bioactivity assays for the conserved lipid A portion of the molecule. Our goal was to develop assays …

Mathematical Models Of Hiv And Hpv Coinfection, Samantha Erwin, Meghna Verma, Vida Abedi, Raquel Hontecillas-Magarzo, Stefan Hoops, Josep Bassaganya-Riera, Stanca M. Ciupe

Biology and Medicine Through Mathematics Conference

No abstract provided.

Needle In The Haystack: Combining Intravital Imaging And Mathematical Modeling To Understand How Vaccine-Induced T Cells Find Malaria-Infected Cells In Murine Livers, Vitaly V. Ganusov, Ian Cockburn, Reka Kelemen

Biology and Medicine Through Mathematics Conference

No abstract provided.

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Hiv-1 Genetic Variation Resulting In The Development Of New Quasispecies Continues To Be Encountered In The Peripheral Blood Of Well-Suppressed Patients., Will Dampier, Michael R Nonnemacher, Joshua Mell, Joshua Earl, Garth D Ehrlich, Vanessa Pirrone, Benjamas Aiamkitsumrit, Wen Zhong, Katherine Kercher, Shendra Passic, Jean W Williams, Jeffrey M Jacobson, Brian Wigdahl

Kimmel Cancer Center Faculty Papers

As a result of antiretroviral therapeutic strategies, human immunodeficiency virus type 1 (HIV-1) infection has become a long-term clinically manageable chronic disease for many infected individuals. However, despite this progress in therapeutic control, including undetectable viral loads and CD4+ T-cell counts in the normal range, viral mutations continue to accumulate in the peripheral blood compartment over time, indicating either low level reactivation and/or replication. Using patients from the Drexel Medicine CNS AIDS Research and Eradication Study (CARES) Cohort, whom have been sampled longitudinally for more than 7 years, genetic change was modeled against to the dominant integrated proviral quasispecies with …

Mycobacterium Cavitary Pneumonia - Not Your Tb Type - A Case Of Rare Mycobacterium Szulgai, Dhwani Pandya Md, Harshal Shah Do, Nicholas Dalessandro Do

Department of Medicine

No abstract provided.

Development Of A Novel Self-Propagating Prssv-Vsv G Hybrid Replicon As A Vector For Inducing Broad Prrsv Protection, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Throughout successive cycles of Pork Check-off funding, our laboratories (Pattnaik’s and Osorio’s labs) have consistently produced new and fundamental information on: (i) the immunologic mechanisms that are important for protection against PRRSV infection, (ii) the structural basis for induction of PRRSV-neutralizing antibodies which are significant for conferring protective immunity, (iii) the possibility of producing a rationally-designed new generation DIVA vaccine that would offer more efficacious protection, and (iv) the presence of conserved B- and T-cell epitopes in the structural and nonstructural proteins (NSPs) of PRRSV.

White Blood Cell Count Versus Temperature As Predictors Of Pediatric Bacteremia, Ashley Ashby, Loren Moscinski

Physician Assistant Capstones, 2016 to 2019

Introduction: Although the prevalence of bacteremia has largely declined with the development of the Haemophilus Influenza Type b (Hib) and pneumococcal vaccines, it continues to be a leading cause of morbidity and mortality in children. Thus, it is crucial to differentiate bacteremia from other illnesses via the clinical picture and laboratory test results. Objective: The purpose of this research was to determine whether there is a clinically significant difference between temperature and white blood cell (WBC) count as determinants of bacteremia in the pediatric population. Methods: A PubMed search was conducted utilizing the following terms and filters: temperature, WBC, pediatrics, …

Fecal Transplant Vs Vancomycin For Recurrent Clostridium Diffile, Lauren M. Taylor, Todd E. Edwards

Physician Assistant Capstones, 2016 to 2019

Objective: To compare fecal transplant and vancomycin in the treatment of recurrent clostridium difficile to determine which has the higher cure rate. Design: Systematic literature review. Methods: Pubmed, Google Scholar, and TRIP database using the search terms “recurrent clostridium difficile.” Filters were implemented in the Pubmed database including: randomized control trials, English, and published in the past 5 years. Records were screened for RCT with fecal transplant and full-text. Results: van Nood et al. revealed an initial cure rate of 81% for the infusion group, and a re-treated cure rate of 94%, compared to the vancomycin alone group of 31% …

Germline Defects Caused By Smed-Boule Rna-Interference Reveal That Egg Capsule Deposition Occurs Independently Of Fertilization, Ovulation, Mating, Or The Presence Of Gametes In Planarian Flatworms, Jessica Kathryne Steiner, Junichi Tasaki, Labib Rouhana

Biological Sciences Faculty Publications

Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue …