Diseases Commons^™

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Characterization Of Corynebacterium Pseudotuberculosis Biovar Equi Isolates Obtained From Cal Poly Horses And Review Of Application Of Transposons To Better Prevent Pigeon Fever In Horses, Irene Hasen

Animal Science

No abstract provided.

Cystic Echinococcoses In Mongolia: Molecular Identification, Serology And Risk Factors, Akira Ito, Temuulen Dorjsuren, Anu Davaasuren, Tetsuya Yanagida, Yasuhito Sako, Kazuhiro Nakaya, Minoru Nakao, Oyun-Erdene Bat-Ochir, Tsendjav Ayushkhuu, Narantuya Bazarragchaa, Nyamkhuu Gonchigsengee, Tiaoying Li, Gurbadam Agvaandaram, Abmed Davaajav, Chinchuluun Boldbaatar, Gantigmaa Chuluunbaatar

Harold W. Manter Laboratory of Parasitology: Library Materials

Abstract

Background

Cystic echinococcosis (CE) is a globally distributed cestode zoonosis that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.) is the major causative agent of CE worldwide, recent molecular epidemiological studies have revealed that E. canadensis is common in countries where camels are present. One such country is Mongolia.

Methodology/Principal Findings

Forty-three human hepatic CE cases that were confirmed histopathologically at the National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by analysis of mitochondrial cox1 gene as being caused by either E. canadensis (n = 31, 72.1%) or E. granulosus s.s. ( …

Urinary Estrogen Metabolites And Self-Reported Infertility In Women Infected With Schistosoma Haematobium, Julio Santos, Maria Joao Gouveia, Nuno Vale, Maria De Lurdes Delgado, Ana Goncalves, Gabriel Rinaldi, Paul J. Brindley, +10 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Schistosomiasis is a neglected tropical disease, endemic in 76 countries, that afflicts more than 240 million people. The impact of schistosomiasis on infertility may be underestimated according to recent literature. Extracts of Schistosoma haematobium include estrogen-like metabolites termed catechol-estrogens that down regulate estrogen receptors alpha and beta in estrogen responsive cells. In addition, schistosome derived catechol-estrogens induce genotoxicity that result in estrogen-DNA adducts. These catechol estrogens and the catechol-estrogen-DNA adducts can be isolated from sera of people infected with S. haematobium. The aim of this study was to study infertility in females infected with S. haematobium and its …

Adrenergic Signaling Regulates Mitochondrial Ca(2+) Uptake Through Pyk2-Dependent Tyrosine Phosphorylation Of The Mitochondrial Ca(2+) Uniporter., Jin O-Uchi, Bong Sook Jhun, Shangcheng Xu, Stephen Hurst, Anna Raffaello, Xiaoyun Liu, Bing Yi, Huiliang Zhang, Polina Gross, Jyotsna Mishra, Alina Ainbinder, Sarah Kettlewell, Godfrey L Smith, Robert T Dirksen, Wang Wang, Rosario Rizzuto, Shey-Shing Sheu

Center for Translational Medicine Faculty Papers

Abstract Aims: Mitochondrial Ca(2+) homeostasis is crucial for balancing cell survival and death. The recent discovery of the molecular identity of the mitochondrial Ca(2+) uniporter pore (MCU) opens new possibilities for applying genetic approaches to study mitochondrial Ca(2+) regulation in various cell types, including cardiac myocytes. Basal tyrosine phosphorylation of MCU was reported from mass spectroscopy of human and mouse tissues, but the signaling pathways that regulate mitochondrial Ca(2+) entry through posttranslational modifications of MCU are completely unknown. Therefore, we investigated α1-adrenergic-mediated signal transduction of MCU posttranslational modification and function in cardiac cells. Results: α1-adrenoceptor (α1-AR) signaling translocated activated proline-rich …

The Development Of A Comprehensive Antifungal Susceptibility Testing Assay For Vulvovaginal Candidiasis Therapy, David Hardaker

Graduate School of Biomedical Sciences Theses and Dissertations

Vulvovaginal candidiasis is the most common fungal infection of the female urogenital tract, commonly caused by Candida albicans and C. glabrata. However, treatment can be difficult when caused by non-albicans strains due to resistance to the oral antifungal drug fluconazole. The mechanism through which strains of Candida, particularly C. glabrata, develop resistance to different antifungal classes has not been completely characterized. The ergosterol biosynthesis pathway, an important component of the cell membrane, is the major target of antifungals such as fluconazole, an inhibitor of the ERG 11 gene. Current research shows that an upregulation of specific genes in C. glabrata …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Neuromodulation Therapy Mitigates Heart Failure Induced Hippocampal Damage, Timothy P. Diperi

Undergraduate Honors Theses

Cardiovascular disease (CVD) is the leading cause of death in the United States. Nearly half of the people diagnosed with heart failure (HF) die within 5 years of diagnosis. Brain abnormalities secondary to CVD have been observed in many discrete regions, including the hippocampus. Nearly 25% of patients with CVD also have major depressive disorder (MDD), and hippocampal dysfunction is a characteristic of both diseases. In this study, the hippocampus and an area of the hippocampal formation, the dentate gyrus (DG), were studied in a canine model of HF. Using this canine HF model previously, we have determined that myocardial …

Propagation Of Oligomeric Α-Synuclein And Amyloid-Β: Implications For Parkinson's And Alzheimer's Diseases, Matthew Stephen Planchard

Master's Theses

The aggregation of amyloidogenic proteins is a critical event in the pathology of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). The proteins α-synuclein (αS) and amyloid-β (Aβ) are involved in the formation of amyloid lesions observed in PD and AD, respectively. Both PD and AD exhibit a significant amount of co-pathology in clinical settings, and the αS and Aβ proteins have been shown to interact in vitro. Recent experimental consensus has shown oligomeric species to be significant, if not primary, sources of toxicity in these diseases. …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres

Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic cancer and …

Suppression Of Basophil Histamine-Release And Other Ige-Dependent Responses In Childhood Schistosoma Mansoni Hookworm Co-Infection, Angela Pinot De Moira, Colin M. Fitzsimmons, Frances M. Jones, Shona Wilson, Pierre Cahen, Edridah Tukahebwa, Harriet Mpairwe, Joseph K. Mwatha, Jeffrey M. Bethony, Per S. Skov, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. The poor correlation between allergen-specific-IgE (asIgE) and clinical signs of allergy in helminth infected populations suggests that helminth infections could protect against allergy by uncoupling asIgE from its effector mechanisms. We investigated this hypothesis in Ugandan schoolchildren coinfected with Schistosoma mansoni and hookworm.

Methods. Skin prick test (SPT) sensitivity to house dust mite allergen (HDM) and current wheeze were assessed pre-anthelmintic treatment. Non-specific (anti-IgE), helminth-specific and HDM-allergen-specific basophil histamine release (HR), plus helminth- and HDM-specific IgE and IgG4 responses were measured pre- and post-treatment.

Results. Non-specific- and helminth-specific-HR, and associations between helminth-specific-IgE and helminth-specific-HR increased post-treatment. Hookworm infection appeared …

Methylation Of Leukocyte Dna And Ovarian Cancer: Relationships With Disease Status And Outcome, Brooke L. Fridley, Sebastian M. Armasu, Mine S. Cicek, Melissa C. Larson, Chen Wang, Stacey J. Winham, Kimberly R. Kalli, Devin C. Koestler

Dartmouth Scholarship

Genome-wide interrogation of DNA methylation (DNAm) in blood-derived leukocytes has become feasible with the advent of CpG genotyping arrays. In epithelial ovarian cancer (EOC), one report found substantial DNAm differences between cases and controls; however, many of these disease-associated CpGs were attributed to differences in white blood cell type distributions. We examined blood-based DNAm in 336 EOC cases and 398 controls; we included only high-quality CpG loci that did not show evidence of association with white blood cell type distributions to evaluate association with case status and overall survival.

Childhood Obesity And Familial Hypercholesterolemia: Genetic Diseases That Contribute To Cardiovascular Disease, Alyssa Caudle

Senior Honors Theses

Childhood obesity occurs as the result of an imbalance between caloric intake and energy expenditure. Genetic risk factors for obesity have become an area of research due to its permanency. Mutated genes such as Fat Mass and Obesity Associated (FTO), Leptin (LEP), Leptin Receptor (LEPR), Melanocortin 4 Receptor (MC4R), Adiponectin C1Q and Collagen Domain Containing (ADIPOQ), Proprotein Convertase Subtilisin/Kexin Type 1 (PCSK1), and Peroxisome Proliferator-Activated Receptor Gamma (PPARG) all contribute to the development of childhood obesity. In the presence of high cholesterol caused by obesity, the genetic condition known as familial hypercholesterolemia is exacerbated. Familial hypercholesterolemia is caused by a …

Inactivation Of Genes For Antigenic Variation In The Relapsing Fever Spirochete Borrelia Hermsii Reduces Infectivity In Mice And Transmission By Ticks, Sandra J. Raffel, James M. Battisti, Robert J. Fischer, Tom G. Schwan

Biological Sciences Faculty Publications

Borrelia hermsii, a causative agent of relapsing fever of humans in western North America, is maintained in enzootic cycles that include small mammals and the tick vector Ornithodoros hermsi. In mammals, the spirochetes repeatedly evade the host’s acquired immune response by undergoing antigenic variation of the variable major proteins (Vmps) produced on their outer surface. This mechanism prolongs spirochete circulation in blood, which increases the potential for acquisition by fast-feeding ticks and therefore perpetuation of the spirochete in nature. Antigenic variation also underlies the relapsing disease observed when humans are infected. However, most spirochetes switch off the bloodstream …

Analysis Of The Regulation And Function Of Cip2a To Identify Candidate Biomarkers For Prostate Cancer, Diana Savoly

Graduate School of Biomedical Sciences Theses and Dissertations

Protein Phosphatase 2A (PP2A) is a tumor suppressor involved in the regulation of several signaling pathways and the cell cycle. PP2A becomes inactivated by several inhibitors, including Cancerous Inhibitor of PP2A (CIP2A). CIP2A has been identified as an oncogene, which is over-expressed in cancers and inhibits PP2A through direct interaction. CIP2A is recognized as a biomarker for cancer; however, it is not cancer-specific. Therefore, we identified and examined the use of CIP2A-regulated proteins as potential biomarkers in prostate cancer to better diagnose prostate cancer in patients. Currently, Prostate Specific Antigen (PSA) is widely used to detect prostate cancer; however, it …

Brain Blast 2014 Poster, Annie Leslie

Brain Blast

Announcement poster for UNE's Brain Blast 2014, a pechakucha-style brain health and safety awareness and learning event.

Vaccinia Virus Flll Mediated Expedition Of Tanapoxvirus Replication In Cell Culture, Yih Wen Goh

Masters Theses

Tanapoxvirus (TPV) produces large but slow-forming plaques as opposed to vaccinia virus (VACV) that forms similar large plaques but more rapidly. A number of genes were identified in VACV, inclucding FllL, A33R, A34R and A36R that contribute to the regulation of virus release and dissemination, and are particularly responsible for the induction of actin tails. Among them, TPV lacks homologs of the FllL and A36R genes. F11Lmediated inhibition of RhoA-mDia signaling was shown to enhance the microtubules dynamics and modulates the cortical actin that assisted in the release of progeny virus from infected cells. To understand the possible effects of …

Brain Blast 2014 Speakers Poster, Annie Leslie

Brain Blast

Poster from UNE's Brain Blast 2014 listing the presenters at this event.

Human African Trypanosomiasis Research Gets A Boost: Unraveling The Tsetse Genome, Serap Aksoy, Geoffrey Attardo, Matt Berriman, Alan Christoffels, Mike Lehane, Dan Masiga, Yeya Toure

All Peer-Reviewed Publications

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a neglected disease that impacts 70 million people distributed over 1.55 million km2 in sub-Saharan Africa [1]. Trypanosoma brucei gambiense accounts for almost 90% of the infections in central and western Africa, the remaining infections being from T. b. rhodesiense in eastern Africa [1]. Furthermore, the animal diseases caused by related parasites inflict major economic losses to countries already strained [2]. The parasites are transmitted to the mammalian hosts through the bite of an infected tsetse fly.

An Immunomics Approach To Schistosome Antigen Discovery: Antibody Signatures Of Naturally Resistant And Chronically Infected Individuals From Endemic Areas, Soraya Gaze, Patrick Driguez, Mark S. Pearson, Tiago Mendes, Denise L. Doolan, Jeffrey M. Bethony, +14 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is a neglected tropical disease that is responsible for almost 300,000 deaths annually. Mass drug administration (MDA) is used worldwide for the control of schistosomiasis, but chemotherapy fails to prevent reinfection with schistosomes, so MDA alone is not sufficient to eliminate the disease, and a prophylactic vaccine is required. Herein, we take advantage of recent advances in systems biology and longitudinal studies in schistosomiasis endemic areas in Brazil to pilot an immunomics approach to the discovery of schistosomiasis vaccine antigens. We selected mostly surface-derived proteins, produced them using an in vitro rapid translation system and then printed them to …

Cardiovascular Health Among Us And Argentine University Students: A Comparative Study Of Behaviors And Risk Factors, Gina Fitzgerald, Gabriella Smith

Seaver College Research And Scholarly Achievement Symposium

Cardiovascular disease for some time has been the leading cause of death in the Western world. Primary prevention is the only way to halt the onset of cardiovascular disease, yet there is little information on the prevalence of risk factors for cardiovascular disease in young adults. This study seeks to evaluate students from the Catholic University of Argentina and Pepperdine University of America for the prevalence of CVD risk factors, as well as knowledge of CVD and daily habits that contribute to heart health. Thus we compared two cultures with very different lifestyles and prevalence of risk factors. We hypothesized …

How To Get The Most From Microarray Data: Advice From Reverse Genomics, Ivan P. Gorlov, Ji-Yeon Yang, Jinyoung Byun, Christopher Logothetis, Olga Y. Gorlova, Kim-Anh Do, Christopher Amos

Dartmouth Scholarship

Whole-genome profiling of gene expression is a powerful tool for identifying cancer-associated genes. Genes differentially expressed between normal and tumorous tissues are usually considered to be cancer associated. We recently demonstrated that the analysis of interindividual variation in gene expression can be useful for identifying cancer associated genes. The goal of this study was to identify the best microarray data–derived predictor of known cancer associated genes. We found that the traditional approach of identifying cancer genes—identifying differentially expressed genes—is not very efficient. The analysis of interindividual variation of gene expression in tumor samples identifies cancer-associated genes more effectively. The results …

Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …

Integrated Assessment Of Predicted Mhc Binding And Cross-Conservation With Self Reveals Patterns Of Viral Camouflage, Lu He, Anne S. De Groot, Andres H. Gutierrez, William D. Martin, Lenny Moise, Chris Bailey-Kellogg

Dartmouth Scholarship

Immune recognition of foreign proteins by T cells hinges on the formation of a ternary complex sandwiching a constituent peptide of the protein between a major histocompatibility complex (MHC) molecule and a T cell receptor (TCR). Viruses have evolved means of "camouflaging" themselves, avoiding immune recognition by reducing the MHC and/or TCR binding of their constituent peptides. Computer-driven T cell epitope mapping tools have been used to evaluate the degree to which articular viruses have used this means of avoiding immune response, but most such analyses focus on MHC-facing ‘agretopes'. Here we set out a new means of evaluating the …

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 …

Comparing Partial Least Square Approaches In Gene-Or Region-Based Association Study For Multiple Quantitative Phenotypes, Zhongshang Yuan, Xiaoshuai Zhang, Fangyu Li, Jinghua Zhao, Fuzhong Xue

Human Biology Open Access Pre-Prints

On thinking quantitatively of complex diseases, there are at least three statistical strategies for association study: single SNP on single trait, gene-or region (with multiple SNPs) on single trait and on multiple traits. The third of which is the most general in dissecting the genetic mechanism underlying complex diseases underpinning multiple quantitative traits. Gene-or region association methods based on partial least square (PLS) approaches have been shown to have apparent power advantage. However, few attempts are developed for multiple quantitative phenotypes or traits underlying a condition or disease, and the performance of various PLS approaches used in association study for …

Celiac Disease As A Model For The Evolution Of Multifactorial Disease In Humans, Aaron Sams, John Hawks

Human Biology Open Access Pre-Prints

Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models …

Genome Of The Human Hookworm Necator Americanus, Yat T. Tang, Xin Gao, Bruce A. Rosa, Sahar Abubucker, Kymberlie Hallsworth-Pepin, Peter J. Hotez, Jeffrey M. Bethony, +23 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, …