Digital Commons Network^™

Ido2 In Immunomodulation And Autoimmune Disease., George C Prendergast, Richard Metz, Alexander J Muller, Lauren M F Merlo, Laura Mandik-Nayak

Department of Microbiology and Immunology Faculty Papers

IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which …

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Characterization Of Severe Fever With Thrombocytopenia Syndrome In Rural Regions Of Zhejiang, China, Lei Zhang, Ling Ye, David M. Ojcius, Xiuyu Lou, Chengwei Wang, Cen Feng, Yi Sun, Zhongfa Wang, Shibo Li, Yanjun Zhang

All Dugoni School of Dentistry Faculty Articles

Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011–2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be …

A Cytoplasmic Rna Virus Generates Functional Viral Small Rnas And Regulates Viral Ires Activity In Mammalian Cells, Kuo-Feng Weng, Chuan-Tien Hung, Po-Ting Hsieh, Mei-Ling L. Li, Guang-Wu Chen, Yu-An Kung, Peng-Nien Huang, Rei-Lin Kuo, Li-Lien Chen, Jing-Yi Lin, Robert Yung-Liang Wang, Shu-Jen Chen, Petrus Tang, Jim-Tong Horng, Hsing-I Huang, Jen-Ren Wang, David M. Ojcius, Gary Brewer, Shin-Ru Shih

All Dugoni School of Dentistry Faculty Articles

The roles of virus-derived small RNAs (vsRNAs) have been studied in plants and insects. However, the generation and function of small RNAs from cytoplasmic RNA viruses in mammalian cells remain unexplored. This study describes four vsRNAs that were detected in enterovirus 71-infected cells using next-generation sequencing and northern blots. Viral infection produced substantial levels (>10⁵ copy numbers per cell) of vsRNA1, one of the four vsRNAs. We also demonstrated that Dicer is involved in vsRNA1 generation in infected cells. vsRNA1 overexpression inhibited viral translation and internal ribosomal entry site (IRES) activity in infected cells. Conversely, blocking vsRNA1 enhanced …

Atypical Presentation Of Actinomyces, Brian Friel Do, Sarah Park Do, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Assessment Of Anthelmintic Efficacy Of Mebendazole In School Children In Six Countries Where Soil-Transmitted Helminths Are Endemic, Bruno Levecke, Antonio Montresor, Marco Albonico, Shaali M. Ame, Jerzy M. Behnke, Jeffrey M. Bethony, +15 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND:

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained …

Necrotizing Fasciitis, Holly Herron

Nursing Student Class Projects (Formerly MSN)

Necrotizing fasciitis also known as necrotizing soft tissue infections (NSTIs) is a rare life-threatening infection that involves the skin and soft tissue. A rapid and accurate diagnosis of NSTIs must be identified by healthcare providers to diminish morbidity and mortality. NSTIs are characterized by progressive necrosis of subcutaneous tissue and fascia involving large areas of tissue (Lin, Chang, Lai, Lin, & Chen, 2013). Hippocrates (500 BC) described necrotizing fasciitis as “diffuse erysipelas caused by trivial accidents [where] flesh, sinews, and bones fell away in large quantities, [leading to] death in many cases” (Lancerotto, Tocco, Salmaso, Vindigni & Bassetto, 2012). In …

Necrotizing Fasciitis: The “Flesh Eating” Disease, John Neukam

Nursing Student Class Projects (Formerly MSN)

Necrotizing fasciitis, often referred to as the “flesh-eating disease”, is a rare bacterial infection with an extremely high mortality rate with symptoms that begin subtle but can quickly ravish the human body.1 While the prevalence of this disease is relatively low, evidence of this disease can be traced back as far as the 5th century BC where it was initially described by Hippocrates.2 It wasn’t until 1952 however that Dr. Bob Wilson termed the disease “necrotizing fasciitis”.3 The rapid progression of this disease and the acute deterioration it causes in a patient is extremely intriguing. This “flesh-eating disease” can present …

Myasthenia Gravis: A Closer Look, Erin L. Ricker

Nursing Student Class Projects (Formerly MSN)

Myasthenia gravis (MG) is a rare, chronic autoimmune disease that affects the neurotransmitter acetylcholine and the acetylcholine receptors at the neuromuscular junction (Mestecky, 2013). MG causes fluctuating skeletal muscle weakness and fatigue. According to the Myasthenia Gravis Foundation of America (MGFA) (2010), 20 per 100,000 patients are diagnosed with MG, although researchers believe several more patients are misdiagnosed or missed entirely. Several neurological disorders have similar clinical presentations to MG making it difficult for inexperienced practitioners to identify and properly diagnose patients. Patients are often misdiagnosed and delayed proper treatment for one to two years after initial presentation of symptoms …

Global Burden Of Tuberculosis, Diana Moses

Nursing Student Class Projects (Formerly MSN)

Tuberculosis (TB) is a major health concern not only in the United States, but in the entire world. TB is an airborne communicable infection which has affected human beings from immemorial times, evidenced by TB being found in the skeletal remains of ancient mummies (Gough & Kaufman, 2011). There are many patho physiological events in TB that concern the entire body, especially the respiratory and immunological systems. According to Knechel, TB prevalence is rising due to the increased number of patients infected with HIV, bacterial resistance to medications, increased international travel and immigration from countries with high prevalence of TB, …

Enterovirus: What Everyone Should Know, Debra Mccorkle

Nursing Student Class Projects (Formerly MSN)

Enterovirus is capturing the attention of everyone; but what is it, who is affected by it, and can it be treated and/or prevented? Like any virus the enterovirus has many different strains. The strain capturing everyone’s attention lately is human enterovirus 68 (HEV68). This strain was first detected in California in 1962 (Oberste et al., 2004). Most cases of HEV68 are mild and do not require medical attention, however some can become severe and may cause serious heart or brain infections according to the Center for Disease Control and Prevention (CDC) website (Updated September 8, 2014). HEV68 is a respiratory …

Ebola: Protecting Healthcare Workers, Martha Mccoy

Nursing Student Class Projects (Formerly MSN)

Ebola is a hemorrhagic disease that has been seen throughout Liberia, but because of international travel it is spreading. Gilsdorf, Morgan and Leitmeyer (2012) researched air travel and reported that, “In 2010, 5.04 billion passengers arrived and departed from 1318 airports worldwide… and travel to and from Africa almost doubled between 1995 and 2005.” (p.1471). In the last few months there have been cases of Ebola reported in Spain and the United States linked to travel. These are recent developments because as of July, 2014 the Center for Disease Control and Prevention (CDC) reported “to date there are no cases …

Ebola Pandemic, Lurajean Cravens

Nursing Student Class Projects (Formerly MSN)

Ebolavirus, or Ebola Virus Disease (EVD), is of the filovirus family causing hemorrhagic fever first discovered in the African country of Zaire in 1976 (Turner, 2014; Hampton, 2014) and has gained global concern and attention since the recent epidemic outbreak in West Africa. There are five known species of Ebola: Zaire, Sudan, Ivory Coast, Bundibugyo and Reston, based on the region of origination. The Zaire species has been identified as the strain responsible for the current outbreak in West Africa, and has spread to Liberia, Sierra Leone, Nigeria and Senegal (Centers for Disease Control and Prevention,2014; Gostin, Lucey & Phelan, …

Chagas Disease: A Dangerous Kiss, Stephen Maynard

Nursing Student Class Projects (Formerly MSN)

Parasitic infections are a common occurrence worldwide and are often more common in low income countries. While these infections are associated with poor compromised communities outside the United States these diseases effect people within the United States and are more common than realized. One specific parasitic infection infects its human host causing Chagas disease. Chagas disease is an infection that occurs from the parasite T. cruzi and was named for the Brazilian physician Carlos Chagas who discovered the disease in 1909 (CDC, 2014). According to the Centers for Disease Control (CDC, 2014), Chagas disease has been targeted as a priority …

Ebola, A Deadly Viral Disease Affecting The West African Country Of Sierra Leone, Unisa Seisay

Nursing Student Class Projects (Formerly MSN)

Presently, there has been an outbreak of Ebola Virus Disease (EVD) in the West African countries of Sierra Leone, Liberia, Nigeria, Senegal and Guinea. The outbreak was first discovered in Guinea in March 21, 2014 and has spread to the neighboring countries. This has resulted in a lot of fatalities and is now considered a global public health concern (WHO, 2014).

Enterococcus Faecalis Endocarditis: A Case Study, Torri Curtis

Nursing Student Class Projects (Formerly MSN)

Infectious endocarditis is an uncommon disease of the heart stemming from a bacterial or fungal infection on the endocardial surface of the heart or heart valve (Pierce, Calkins, & Thornton, 2012). From review of the literature, infective endocarditis is fairly uncommon and may be difficult to initially diagnose. Per Sabe, Shrestha, and Menon, occurrence of infective endocarditis (IE) is nearly 0.9-6.2 per 100,000 persons per year (2013). Several preexisting conditions such as aging, heart valve disease, implantable cardiac devices, a history of heart disease such as rheumatic fever, and invasive procedures can put a patient at higher risk for IE …

Enterovirus D68, Kimberly Meyers

Nursing Student Class Projects (Formerly MSN)

Enterovirus D68 (EVD68) “belongs to the family Picornaviridae, genus Enterovirus, and species Human enterovirus D: (Kaida et al.,2011, para.2). It is a small nonenveloped RNA virus (Xiang et al., 2012). EVD68 “shares characteristics with rhinoviruses, such as infection of the respiratory tract and acid lability” (Lauinger et al., 2012). There is no specific treatment for EVD68. Since the infection is caused by a virus, antibiotics would be ineffective. There are no antiviral medications currently available to treat EVD68 (Herold, 2014). Treatment may include antipyretics, cough medicines, bronchodilators, oxygen, and mechanical ventilation if required.

Ascaris Lumbricoides: The Unforeseen Diagnosis, Suzette Maynard

Nursing Student Class Projects (Formerly MSN)

Infections from Ascaris lumbricoides have become very prevalent in lesser developed countries. These infections are believed to migrate into the United States through the border with Mexico, and immigration from other countries, through increased world travel and international adoptions (Cardenas et al., 2010). A. lumbricoides have been found to cause cases in the United States, one being in Westerville, Ohio (J. Leonard, personal communication, September 6, 2014). As the world has become smaller, it has become imperative that as a nation we are able to prepare for infections that are popular outside the United States. The first step in preparing …

Host Cell Death In Legionella Pneumophila Pathogenesis And Immunity, Wenhan Zhu

Open Access Dissertations

Legionella pneumophila is an intracellular pathogen that causes a severe, atypical pneumonia termed Legionnaires' disease. Upon entering the host cell, L. pneumophila resides in a membrane-bound vacuole, in which the bacterium evades lysosomal fusion and replicates. The establishment of the vacuole requires the Dot/Icm (Defect in organelle trafficking/ intracellular multiplication) transport system, which translocates a large number of substrates into host cells to re-orchestrate various cellular processes, such as intracellular trafficking, protein synthesis and host cell death pathways. Therefore, a key step in understanding the biology of Legionella is to dissect the mechanisms of action of the Dot/Icm substrates. By …

Contribution Of Teg49 Small Rna In The 5′ Upstream Transcriptional Region Of Sara To Virulence In Staphylococcus Aureus, Samin Kim, Dindo Reyes, Marie Beaume, Patrice Francois, Ambrose Cheung

Dartmouth Scholarship

High-throughput RNA sequencing technology has found the 5' untranslated region of sarA to contain two putative small RNAs (sRNAs), designated teg49 and teg48. Northern blot analysis disclosed that teg49 and teg48 were detectable within the P3-P1 and P1 sarA promoter regions, respectively. Focusing on teg49, we found that this sRNA, consisting of 196 nucleotides, is transcribed in the same direction as the sarA P3 transcript. The expression of both P3 and teg49 transcripts is dependent on sigB and cshA, which encodes a DEAD box RNA helicase. Within the sRNA teg49, there are two putative hairpin-loop structures, HP1 and HP2. Transversion …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …

Differential Spatial Repositioning Of Activated Genes In Biomphalaria Glabrata Snails Infected With Schistosoma Mansoni, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Joanna M. Bridger, Matty Knight

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro thatBiomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their …

A Rational Framework For Evaluating The Next Generation Of Vaccines Against Mycobacterium Avium Subspecies Paratuberculosis, John P. Bannantine, Murray E. Hines Ii, Luiz E. Bermudez, Adel M. Talaat, Srinand Sreevatsan, Judith R. Stabel, Yung-Fu Chang, Paul M. Coussens, Raúl G. Barletta, William C. Davis, Desmond M. Collins, Yrjö T. Gröhn, Vivek Kapur

School of Veterinary and Biomedical Sciences: Faculty Publications

Since the early 1980s, several investigations have focused on developing a vaccine against Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of Johne's disease in cattle and sheep. These studies used whole-cell inactived vaccines that have proven useful in limiting disease progression, but have not prevented infection. In contrast, modified live vaccines that invoke a Th1 type immune response, may improve protection against infection. Spurred by recent advances in the ability to create defined knockouts in MAP, several independent laboratories have developed modified live vaccine candidates by transcriptional mutation of virulence and metablolic genes in MAP. In order to accelerate …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Diminished Humoral Responses Against And Reduced Gene Expression Levels Of Human Endogenous Retrovirus-K (Herv-K) In Psoriasis, Rashmi Gupta, Henri-Alexandre Michaud, Xue Zeng, Maya Debbaneh, Sarah T. Arron, R. Brad Jones, Christopher E. Ormsby, Douglas F. Nixon, Wilson Liao

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Ifn-Gamma Au-Rich Element Removal Promotes Chronic Ifn-Gamma Expression And Autoimmunity In Mice, Deborah L. Hodge, Cyril Berthet, Vincenzo Coppola, Wolfgang Kastenmüller, Matthew D. Buschman, Paul M. Schaughency, Hidekazu Shirota, Anthony J. Scarzello, Jeff J. Subleski, Miriam R. Anver, John R. Ortaldo, Fanching Lin, Della A. Reynolds, Michael E. Sanford, Philipp Kaldis, Lino Tessarollo, Dennis M. Klinman, Howard A. Young

United States Public Health Resources

We generated a mouse model with a 162 nt AU-rich element (ARE) region deletion in the 3' untranslated region (3'UTR) of the interferon-gamma (IFN-γ) gene that results in chronic circulating serum IFN-γ levels. Mice homozygous for the ARE deletion (ARE-Del) (-/-) present both serologic and cellular abnormalities typical of patients with systemic lupus erythematosus (SLE). ARE-Del(-/-) mice display increased numbers of pDCs in bone marrow and spleen. Addition of IFN-γ to Flt3-ligand (Flt3L) treated in vitro bone marrow cultures results in a 2-fold increase in pDCs with concurrent increases in IRF8 expression. Marginal zone B (MZB) cells and marginal zone …

Impact Of Distinct Poxvirus Infections On The Specificities And Functionalities Of Cd4+ T Cell Responses., Nicholas A Siciliano, Adam R Hersperger, Aimee M Lacuanan, Ren-Huan Xu, John Sidney, Alessandro Sette, Luis J Sigal, Laurence C. Eisenlohr

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The factors that determine CD4+ T cell (TCD4+) specificities, functional capacity, and memory persistence in response to complex pathogens remain unclear. We explored these parameters in the C57BL/6 mouse through comparison of two highly related (>92% homology) poxviruses: ectromelia virus (ECTV), a natural mouse pathogen, and vaccinia virus (VACV), a heterologous virus that nevertheless elicits potent immune responses. In addition to elucidating several previously unidentified major histocompatibility complex class II (MHC-II)-restricted epitopes, we observed many qualitative and quantitative differences between the TCD4+ repertoires, including responses not elicited by VACV despite complete sequence conservation. In addition, we observed functional …

Disrupted Human–Pathogen Co-Evolution: A Model For Disease, Nuri Kodaman, Rafal S. Sobota, Robertino Mera, Barbara G. Schneider, Scott M. Williams

Dartmouth Scholarship

A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease …

The Microtubule-Associated Protein, Eb1, Links Aim2 Inflammasomes With Autophagy-Dependent Secretion, Li-Jie Wang, Hsin-Yi Huang, Meng-Pin Huang, Willisa Liou, Ya-Ting Chang, Chih-Ching Wu, David M. Ojcius, Yu-Sun Chang

All Dugoni School of Dentistry Faculty Articles

Inflammasomes are multi-protein complexes that regulate chronic inflammation-associated diseases by inducing interleukin-1 β (IL-1β) secretion. Numerous components involved in inflammasome activation have been identified, but the mechanisms of inflammasome-mediated IL-1β secretion have not yet been fully explored. Here, we demonstrate that end-binding protein 1 (EB1), which is required for activation of AIM2 inflammasome complex, links the AIM2 inflammasome to autophagy-dependent secretion. Imaging studies revealed that AIM2 inflammasomes colocalize with microtubule organizing centers and autophagosomes. Biochemical analyses showed that poly(dA-dT)-activated AIM2 inflammasomes induce autophagy and IL-1β secretion in an LC3-dependent fashion. Furthermore, depletion of EB1 decreases autophagic shedding and intracellular trafficking. …

Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola

Dartmouth Scholarship

The worldwide administration of bivalent and quadrivalent HPV vaccines has resulted in cross-protection against non-vaccine HPV types. Infection with multiple HPV types may offer similar cross-protection in the natural setting. We hypothesized that infections with two or more HPV types from the same species, and independently, infections with two or more HPV types from different species, associate with protection from high-grade lesions.