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Immunology and Infectious Disease

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Articles 91 - 120 of 150

Full-Text Articles in Medical Microbiology

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout Dec 2015

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites. …


Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors Nov 2015

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …


A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe Oct 2015

A Tail Of Two Phages: Genomic And Functional Analysis Of Listeria Monocytogenes Phages Vb_Lmos_188 And Vb_Lmos_293 Reveal The Receptor-Binding Proteins Involved In Host Specificity, Aidan Casey, Kieran Jordan, Horst Neve, Aidan Coffey, Olivia Mcauliffe

Department of Biological Sciences Publications

The physical characteristics of bacteriophages establish them as viable candidates for downstream development of pathogen detection assays and biocontrol measures. To utilize phages for such purposes, a detailed knowledge of their host interaction mechanisms is a prerequisite. There is currently a wealth of knowledge available concerning Gram-negative phage-host interaction, but little by comparison for Gram-positive phages and Listeria phages in particular. In this research, the lytic spectrum of two recently isolated Listeria monocytogenes phages (vB_LmoS_188 and vB_LmoS_293) was determined, and the genomic basis for their observed serotype 4b/4e host-specificity was investigated using comparative genomics. The late tail genes of these …


Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors Oct 2015

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …


Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More Oct 2015

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …


The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony Aug 2015

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …


Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More Jul 2015

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) …


Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski May 2015

Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski

Honors Scholar Theses

Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …


A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna Apr 2015

A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically …


Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium Apr 2015

Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.


Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh Apr 2015

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.


Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon Jan 2015

Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection.

Methods

Genomic Fragment 2.23 containing a DAF-16 binding …


An Improved Method For Generating Axenic Entomopathogenic Nematodes., Shruti Yadav, Upasana Shokal, Steven Forst, Ioannis Eleftherianos Jan 2015

An Improved Method For Generating Axenic Entomopathogenic Nematodes., Shruti Yadav, Upasana Shokal, Steven Forst, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Steinernema carpocapsae are parasitic nematodes that invade and kill insects. The nematodes are mutualistically associated with the bacteria Xenorhabdus nematophila and together form an excellent model to study pathogen infection processes and host anti-nematode/antibacterial immune responses. To determine the contribution of S. carpocapsae and their associated X. nematophila to the successful infection of insects as well as to investigate the interaction of each mutualistic partner with the insect immune system, it is important to develop and establish robust methods for generating nematodes devoid of their bacteria.

FINDINGS: To produce S. carpocapsae nematodes without their associated X. nematophila bacteria, we …


Of Monkeys And Men: Immunomic Profiling Of Sera From Humans And Non-Human Primates Resistant To Schistosomiasis Reveals Novel Potential Vaccine Candidates., Mark S Pearson, Luke Becker, Patrick Driguez, Neil D Young, Soraya Gaze, Jeffrey M. Bethony, +12 Additional Authors Jan 2015

Of Monkeys And Men: Immunomic Profiling Of Sera From Humans And Non-Human Primates Resistant To Schistosomiasis Reveals Novel Potential Vaccine Candidates., Mark S Pearson, Luke Becker, Patrick Driguez, Neil D Young, Soraya Gaze, Jeffrey M. Bethony, +12 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well …


The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa Jan 2015

The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms …


Comparison Of Findings Using Ultrasonography And Cystoscopy In Urogenital Schistosomiasis In A Public Health Centre In Rural Angola, Julio Santos, Jacinta Chaves, Heriberto Araujo, Nuno Vale, Jose Manuel Costa, Paul J. Brindley, Carlos Lopes, Jean Naples, Clive Shiff, Jorge Dupret, Lucio Lara Santos Jan 2015

Comparison Of Findings Using Ultrasonography And Cystoscopy In Urogenital Schistosomiasis In A Public Health Centre In Rural Angola, Julio Santos, Jacinta Chaves, Heriberto Araujo, Nuno Vale, Jose Manuel Costa, Paul J. Brindley, Carlos Lopes, Jean Naples, Clive Shiff, Jorge Dupret, Lucio Lara Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the gold-standard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10 - 40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease.

Objective. To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health …


Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley Jan 2015

Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.


P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos Dec 2014

P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.

Methodology/Principal Findings

Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder …


Strengthening Neglected Tropical Disease Research Through Enhancing Research-Site Capacity: An Evaluation Of A Novel Web Application To Facilitate Research Collections, Tanzin Furtado, Samuel Franzen, Francois Van Loggerenberg, Gwenaelle Carn, Shannon Grahek, Megan Mcbride, Maureen Power, Barbara Savarese, Margaret Ann Snowden, Gwynn Stevens, Almarie Uys, Trudie Lang Nov 2014

Strengthening Neglected Tropical Disease Research Through Enhancing Research-Site Capacity: An Evaluation Of A Novel Web Application To Facilitate Research Collections, Tanzin Furtado, Samuel Franzen, Francois Van Loggerenberg, Gwenaelle Carn, Shannon Grahek, Megan Mcbride, Maureen Power, Barbara Savarese, Margaret Ann Snowden, Gwynn Stevens, Almarie Uys, Trudie Lang

Microbiology, Immunology, and Tropical Medicine Faculty Publications

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 Oct 2014

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 …


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 Sep 2014

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 …


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 Sep 2014

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 …


Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford Jun 2014

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …


Association Between Symptomatic Vulvovaginal Candidiasis And Hiv Rna Levels In Plasma And Genital Secretions Among Women On Haart, Teke Apalata, William H. Carr, Benjamin Longo-Mbenza, Willem A. Sturm, P. Moodley Jun 2014

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

Publications and Research

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

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

Results. Plasma HIV RNA …


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 May 2014

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 …


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 Apr 2014

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 …


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 Mar 2014

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 …


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 Mar 2014

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, …


Suppression Of Aquaporin, A Mediator Of Water Channel Control In The Carcinogenic Liver Fluke, Opisthorchis Viverrini, Sirikanda Thanasuwan, Supawadee Piratae, Paul J. Brindley, Alex Loukas, Sasithorn Kaewkes, Thewarach Laha Jan 2014

Suppression Of Aquaporin, A Mediator Of Water Channel Control In The Carcinogenic Liver Fluke, Opisthorchis Viverrini, Sirikanda Thanasuwan, Supawadee Piratae, Paul J. Brindley, Alex Loukas, Sasithorn Kaewkes, Thewarach Laha

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Opisthorchiasis and Opisthorchis viverrini-associated bile duct cancer represent major public health threats in Thailand and Laos. The tegument of this food borne fluke plays pivotal roles in parasite metabolism, homeostasis and osmoregulation. Excretory/secretory products also pass from the fluke to the biliary environment, products that likely underlie pathogenesis of liver fluke infection. Aquaporins (AQPs), belong to the major intrinsic protein superfamily of integral plasma membrane channel proteins that selectively transport water across cell membranes. AQPs play key roles as water and ion transport channels through the tegument of helminth parasites.

Methods

Here, two forms of AQP mRNAs from the …


Schistosomes And Snails: A Molecular Encounter, Matty Knight, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Edwin C. Odoemelam, Andre N. Miller, Joanna M. Bridger Jan 2014

Schistosomes And Snails: A Molecular Encounter, Matty Knight, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Edwin C. Odoemelam, Andre N. Miller, Joanna M. Bridger

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria glabrata snails play an integral role in the transmission of Schistosoma mansoni, the causative agent for human schistosomiasis in the Western hemisphere. For the past two decades, tremendous advances have been made in research aimed at elucidating the molecular basis of the snail/parasite interaction. The growing concern that there is no vaccine to prevent schistosomiasis and only one effective drug in existence provides the impetus to develop new control strategies based on eliminating schistosomes at the snail-stage of the life cycle. To elucidate why a given snail is not always compatible to each and every schistosome it encounters, B. …