Digital Commons Network^™

Systematic Review Of Gastrointestinal Nematodes Of Horses From Australia, Muhammad A. Saeed, Ian Beveridge, Ghazanfar Abbas, Anne Beasley, Jenni Bauquier, Edwina Wilkes, Caroline Jacobson, Kris J. Hughes, Charles El-Hage, Ryan O'Handley, John Hurley, Lucy Cudmore, Peter Carrigan, Lisa Walter, Brett Tennent-Brown, Martin K. Nielsen, Abdul Jabbar

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Equine gastrointestinal nematodes (GINs) have been the subject of intermittent studies in Australia over the past few decades. However, comprehensive information on the epidemiology of equine GINs, the efficacy of available anthelmintic drugs and the prevalence of anthelmintic resistance (AR) in Australasia is lacking. Herein, we have systematically reviewed existing knowledge on the horse GINs recorded in Australia, and main aspects of their pathogeneses, epidemiology, diagnoses, treatment and control.

Methods: Six electronic databases were searched for publications on GINs of Australian horses that met our inclusion criteria for the systematic review. Subsets of publications were subjected to review epidemiology, …

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …

Alterations In Phosphorylation Of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection., Elizabeth K K Glennon, Laura S Austin, Nadia Arang, Heather S Kain, Fred D Mast, Kamalakannan Vijayan, John D Aitchison, Stefan H I Kappe, Alexis Kaushansky

Articles, Abstracts, and Reports

Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast …

Mapping Of Lymphatic Filariasis In Loiasis Areas: A New Strategy Shows No Evidence For Wuchereria Bancrofti Endemicity In Cameroon, Samuel Wanji, Mathias Eyong Esum, Abdel Jelil Njouendou, Amuam Andrew Mbeng, Patrick W Chounna Ndongmo, Raphael Awah Abong, Jerome Fru, Fanny F. Fombad, Gordon Takop Nchanji, Glory Ngongeh, Narcisse V. Ngandjui, Peter Ivo Enyong, Helen Storey, Kurt C. Curtis, Kerstin Fischer, Joseph R. Fauver, Daphne Lew, Charles W. Goss, Peter U. Fischer

Journal Articles: Epidemiology

BACKGROUND: Mapping of lymphatic filariasis (LF) caused by Wuchereria bancrofti largely relies on the detection of circulating antigen using ICT cards. Several studies have recently shown that this test can be cross-reactive with sera of subjects heavily infected with Loa loa and thus mapping results in loiasis endemic areas may be inaccurate.

METHODOLOGY/PRINCIPAL FINDINGS: In order to develop an LF mapping strategy for areas with high loiasis prevalence, we collected day blood samples from 5,001 subjects residing in 50 villages that make up 6 health districts throughout Cameroon. Antigen testing using Filarial Test Strip (FTS, a novel platform that uses …

De Novo Assembly Of The Brugia Malayi Genome Using Long Reads From A Single Minion Flowcell, Joseph R. Fauver, John Martin, Gary J. Weil, Makedonka Mitreva, Peter U. Fischer

Journal Articles: Epidemiology

Filarial nematode infections cause a substantial global disease burden. Genomic studies of filarial worms can improve our understanding of their biology and epidemiology. However, genomic information from field isolates is limited and available reference genomes are often discontinuous. Single molecule sequencing technologies can reduce the cost of genome sequencing and long reads produced from these devices can improve the contiguity and completeness of genome assemblies. In addition, these new technologies can make generation and analysis of large numbers of field isolates feasible. In this study, we assessed the performance of the Oxford Nanopore Technologies MinION for sequencing and assembling the …

Diagnosis Of Schistosoma Mansoni Infections: What Are The Choices In Brazilian Low-Endemic Areas?, Vanessa Silva-Moraes, Lisa M. Shollenberger, Liliane Maria Vidal Siqueira, William Castro-Borges, Donald A. Harn, Rafaella Fortini Queiroz E. Grenfell, Ana Lucia Teles Rabello, Paulo Marcos Zech Coelho

Biological Sciences Faculty Publications

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then …

Field Testing Integrated Interventions For Schistosomiasis Elimination In The People's Republic Of China: Outcomes Of A Multifactorial Cluster-Randomized Controlled Trial, Gail M. Williams, Yue-Sheng Li, Darren J. Gray, Zheng-Yuan Zhao, Donald A. Harn, Lisa M. Shollenberger, Sheng-Ming Li, Xinglin Yu, Zeng Feng, Jia-Gang Guo, Jie Zhou, Yu-Lan Dong, Yuan Li, Biao Guo, Patrick Driguez, Marina Harvie, Hong You, Allen G. Ross, Donald P. Mcmanus

Biological Sciences Faculty Publications

Despite significant progress, China faces the challenge of re-emerging schistosomiasis transmission in currently controlled areas due, in part, to the presence of a range of animal reservoirs, notably water buffalo and cattle, which can harbor Schistosoma japonicum infections. Environmental, ecological and social-demographic changes in China, shown to affect the distribution of oncomelanid snails, can also impact future schistosomiasis transmission. In light of their importance in the S. japonicum, lifecycle, vaccination has been proposed as a means to reduce the excretion of egg from cattle and buffalo, thereby interrupting transmission from these reservoir hosts to snails. A DNA-based vaccine (SjCTPI) …

Serological Proteomic Screening And Evaluation Of A Recombinant Egg Antigen For The Diagnosis Of Low-Intensity Schistosoma Mansoni Infections In Endemic Area In Brazil, Vanessa Silva-Moraes, Lisa Marie Shollenberger, William Castro-Borges, Ana Lucia Teles Rabello, Donald A. Harn, Lia Carolina Soares Medeiros, Wander De Jesus Jeremias, Liliane Maria Vidal Siqueira, Caroline Stephane Salviano Pereira, Maria Luysa Camargos Pedrosa, Nathalie Bonatti Franco Almeida, Aureo Almeida, Jose Roberto Lambertucci, Nidia Francisca De Figueiredo Carneiro, Paulo Marcos Zech Coelho, Refaella Fortini Queiroz Grenfell

Biological Sciences Faculty Publications

Background

Despite decades of use of control programs, schistosomiasis remains a global public health problem. To further reduce prevalence and intensity of infection, or to achieve the goal of elimination in low-endemic areas, there needs to be better diagnostic tools to detect low-intensity infections in low-endemic areas in Brazil. The rationale for development of new diagnostic tools is that the current standard test Kato-Katz (KK) is not sensitive enough to detect low-intensity infections in low-endemic areas. In order to develop new diagnostic tools, we employed a proteomics approach to identify biomarkers associated with schistosome-specific immune responses in hopes of developing …

A Herpesvirus Encoded Qa-1 Mimic Inhibits Natural Killer Cell Cytotoxicity Through Cd94/Nkg2a Receptor Engagement, Xiaoli Wang, Sytse J. Piersma, Christopher A. Nelson, Ya-Nan Dai, Ted Christensen, Eric Lazear, Liping Yang, Marjolein Sluijter, Thorbald Van Hall, Ted H. Hansen, Wayne M. Yokoyama, Daved H. Fremont

Open Access Publications

A recurrent theme in viral immune evasion is the sabotage of MHC-I antigen presentation, which brings virus the concomitant issue of 'missing-self' recognition by NK cells that use inhibitory receptors to detect surface MHC-I proteins. Here, we report that rodent herpesvirus Peru (RHVP) encodes a Qa-1 like protein (pQa-1) via RNA splicing to counteract NK activation. While pQa-1 surface expression is stabilized by the same canonical peptides presented by murine Qa-1, pQa-1 is GPI-anchored and resistant to the activity of RHVP pK3, a ubiquitin ligase that targets MHC-I for degradation. pQa-1 tetramer staining indicates that it recognizes CD94/NKG2A receptors. Consistently, …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst

Articles, Abstracts, and Reports

The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level …

Flexible And Fast Mapping Of Peptides To A Proteome With Proteomapper., Luis Mendoza, Eric W Deutsch, Zhi Sun, David S Campbell, David Shteynberg, Robert L Moritz

Articles, Abstracts, and Reports

Bottom-up proteomics relies on the proteolytic or chemical cleavage of proteins into peptides, the identification of those peptides via mass spectrometry, and the mapping of the identified peptides back to the reference proteome to infer which possible proteins are identified. Reliable mapping of peptides to proteins still poses substantial challenges when considering similar proteins, protein families, splice isoforms, sequence variation, and possible residue mass modifications, combined with an imperfect and incomplete understanding of the proteome. The ProteoMapper tool enables a comprehensive and rapid mapping of peptides to a reference proteome. The indexer component creates a segmented index for an input …

Vwa Proteins Of Leptospira Interrogans Induce Hemorrhage In Leptospirosis By Competitive Inhibition Of Vwf/Gpib-Mediated Platelet Aggregation., Jia-Qi Fang, Muhammad Imran, Wei-Lin Hu, David M. Ojcius, Yang Li, Yu-Mei Ge, Kai-Xuan Li, Xu'ai Lin, Jie Yan

All Dugoni School of Dentistry Faculty Articles

BACKGROUD: Leptospira interrogans is the major causative agent of leptospirosis, a worldwide zoonotic disease. Hemorrhage is a typical pathological feature of leptospirosis. Binding of von Willebrand factor (vWF) to platelet glycoprotein-Ibα (GPIbα) is a crucial step in initiation of platelet aggregation. The products of L. interrogans vwa-I and vwa-II genes contain vWF-A domains, but their ability to induce hemorrhage has not been determined.

METHODS: Human (Hu)-platelet- and Hu-GPIbα-binding abilities of the recombinant proteins expressed by L. interrogans strain Lai vwa-I and vwa-II genes (rLep-vWA-I and rLep-vWA-II) were detected by flowcytometry, surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Hu-platelet …

Multistate Infestation With The Exotic Disease-Vector Tick Haemaphysalis Longicornis - United States, August 2017-September 2018, C. B. Beard, James Occi, Denise L. Bonilla, Andrea M. Egizi, Dina M. Fonseca, Gary P. Wormser, William Halperin

NYMC Faculty Publications

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six …

Haptoglobin Improves Shock, Lung Injury, And Survival In Canine Pneumonia, Kenneth E. Remy, Irene Cortés-Puch, Steven B. Solomon, Junfeng Sun, Benjamin M. Pockros, Jing Feng, Juan J. Lertora, Roy R. Hantgan, Xiaohua Liu, Andreas Perlegas, H. Shaw Warren, Mark T. Gladwin, Daniel B. Kim-Shapiro, Harvey G. Klein, Charles Natanson

Open Access Publications

During the last half-century, numerous antiinflammatory agents were tested in dozens of clinical trials and have proven ineffective for treating septic shock. The observation in multiple studies that cell-free hemoglobin (CFH) levels are elevated during clinical sepsis and that the degree of increase correlates with higher mortality suggests an alternative approach. Human haptoglobin binds CFH with high affinity and, therefore, can potentially reduce iron availability and oxidative activity. CFH levels are elevated over approximately 24-48 hours in our antibiotic-treated canine model of S. aureus pneumonia that simulates the cardiovascular abnormalities of human septic shock. In this 96-hour model, resuscitative treatments, …

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty, Staff and Students Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

A Novel Fas-Binding Outer Membrane Protein And Lipopolysaccharide Of Leptospira Interrogans Induce Macrophage Apoptosis Through The Fas/Fasl-Caspase-8/-3 Pathway., Peng Du, Shi-Jun Li, David M. Ojcius, Kai-Xuan Li, Wei-Lin Hu, Xu'ai Lin, Ai-Hua Sun, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Leptospira interrogans is the major causative agent of leptospirosis, an emerging, globally spreading zoonotic infectious disease. The pathogen induces macrophage apoptosis, but the molecular basis and mechanism remain unknown. In the present study, we found that L. interrogans caused apoptosis of phagocytosis-inhibited macrophages, and the product of the L. interrogans LB047 gene (Lep-OMP047) was the unique protein captured by mouse and human Fas proteins. The recombinant expressed Lep-OMP047 (rLep-OMP047) strongly bound mouse and human Fas proteins with equilibrium association constant (K

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the …

Trpv1 And The Mcp-1/Ccr2 Axis Modulate Post-Uti Chronic Pain., John Rosen, Ryan E. Yaggie, Patrick J. Woida, Richard J. Miller, Anthony J. Schaeffer, David J. Klumpp

Manuscripts, Articles, Book Chapters and Other Papers

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas …

Expression, Purification, And Inhibition Profile Of Dihydrofolate Reductase From The Filarial Nematode Wuchereria Bancrofti, Andrew M. Tobias, Dea Toska, Keith Lange, Tyler Eck, Rohit Bhat, Cheryl A. Janson, David P. Rotella, Ueli Gubler, Nina M. Goodey

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

Filariasis is a tropical disease caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. Known inhibitors of dihydrofolate reductase (DHFR) have been previously shown to kill Brugia malayi nematodes and to inhibit Brugia malayi DHFR (BmDHFR) at nanomolar concentrations. These data suggest that BmDHFR is a potential target for the treatment of filariasis. Here, protocols for cloning, expression and purification of Wuchereria bancrofti DHFR (WbDHFR) were developed. The Uniprot entry J9F199-1 predicts a 172 amino acid protein for WbDHFR but alignment of this sequence to the previously described BmDHFR shows that this WbDHFR sequence lacks a crucial, conserved 13 …

Comparative Analysis Of Microbial Sensing Molecules In Mucosal Tissues With Aging, Octavio A. Gonzalez, Sreenatha S. Kirakodu, Michael John Novak, A. J. Stromberg, L. Orraca, J. Gonzalez-Martinez, A. Burgos, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. It is now well recognized that an array of host-derived pattern recognition receptors (PRRs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (MAMP). This report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing molecules related to aging in healthy gingival tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival tissues obtained, RNA isolated and microarray analysis conducted for gene expression of …

Sooty Mangabey Genome Sequence Provides Insight Into Aids Resistance In A Natural Siv Host, David Palesch, Steven E. Bosinger, Gregory K. Tharp, Thomas H. Vanderford, Mirko Paiardini, Ann Chahroudi, Zachary P. Johnson, Frank Kirchhoff, Beatrice H. Hahn, Robert B. Norgren, Nirav B. Patel, Donald L. Sodora, Reem A. Dawoud, Caro-Beth Stewart, Sara M. Seepo, R. Alan Harris, Yue Liu, Muthuswamy Raveendran, Yi Han, Adam English, Gregg W.C. Thomas, Matthew W. Hahn, Lenore Pipes, Christopher E. Mason, Donna M. Muzny, Richard A. Gibbs, Daniel Sauter, Kim Worley, Jeffrey Rogers, Guido Silvestri

Journal Articles: Genetics, Cell Biology & Anatomy

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a …

Variation In Competence For Zikv Transmission By Aedes Aegypti And Aedes Albopictus In Mexico, Selene M. Garcia-Luna, James Weger-Lucarelli, Claudia Rückert, Reyes A. Murrieta, Michael C. Young, Alex D. Byas, Joseph R. Fauver, Rushika Perera, Adriana E. Flores-Suarez, Gustavo Ponce-Garcia, Americo D. Rodriguez, Gregory D. Ebel, William C. Black

Journal Articles: Epidemiology

BACKGROUND: ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV.

METHODOLOGY/PRINCIPAL FINDINGS: Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59-Asian lineage) VC. Mexican …

Schistosoma Mansoni And Other Intestinal Parasitic Infections In Schoolchildren And Vervet Monkeys In Lake Ziway Area, Ethiopia, Dejene Teklemariam, Mengistu Legesse, Abraham Degarege, Song Liang, Berhanu Erko

Journal Articles: Epidemiology

OBJECTIVE: To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia.

RESULTS: Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni …

Catching Chances: The Movement To Be On The Ground And Research Ready Before An Outbreak, David Brett-Major, James V. Lawler

Journal Articles: Epidemiology

After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014⁻2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therapeutic products, none are available on commercial shelves. This …

Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin …

Autonomic Dysreflexia After Spinal Cord Injury: Systemic Pathophysiology And Methods Of Management, Khalid C. Eldahan, Alexander G. Rabchevsky

Physiology Faculty Publications

Traumatic spinal cord injury (SCI) has widespread physiological effects beyond the disruption of sensory and motor function, notably the loss of normal autonomic and cardiovascular control. Injury at or above the sixth thoracic spinal cord segment segregates critical spinal sympathetic neurons from supraspinal modulation which can result in a syndrome known as autonomic dysreflexia (AD). AD is defined as episodic hypertension and concomitant baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in the decentralized cord. This condition is often triggered by noxious yet unperceived visceral or somatic stimuli below the injury level and if severe enough can require immediate medical attention. …

Onchocerca Volvulus: The Road From Basic Biology To A Vaccine., Sara Lustigman, Benjamin L. Makepeace, Thomas R. Klei, Simon A. Babayan, Peter Hotez, David Abraham, Maria Elena Bottazzi

Department of Microbiology and Immunology Faculty Papers

Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into …

Fluorescence-Reported Allelic Exchange Mutagenesis Reveals A Role For Chlamydia Trachomatis Tmea In Invasion That Is Independent Of Host Ahnak, M. J. Mckuen, Konrad E. Mueller, Y. S. Bae, Kenneth A. Fields

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Development of approaches to genetically manipulate Chlamydia is fostering important advances in understanding pathogenesis. Fluorescence-reported allelic exchange mutagenesis (FRAEM) now enables the complete deletion of specific genes in C. trachomatis L2. We have leveraged this technology to delete the coding sequences for a known type III effector. The evidence provided here indicates that CT694/CTL0063 is a virulence protein involved in chlamydial invasion. Based on our findings, we designate the gene product corresponding to ct694-ctl0063 translocated membrane-associated effector A (TmeA). Deletion of tmeA did not impact development of intracellular chlamydiae. However, the absence of TmeA manifested as a decrease in infectivity …

Interleukin-17 Limits Hypoxia-Inducible Factor 1Α And Development Of Hypoxic Granulomas During Tuberculosis, Racquel Domingo-Gonzalez, Shibali Das, Kristin L. Griffiths, Mushtaq Ahmed, Monika Bambouskova, Suhas Gondi, Noor Al-Hammadi, Reid Townsend, Maxim N. Artyomov, Shabaana A. Khader, Et Al.

Open Access Publications

Mycobacterium tuberculosis (Mtb) is a global health threat, compounded by the emergence of drug-resistant strains. A hallmark of pulmonary tuberculosis (TB) is the formation of hypoxic necrotic granulomas, which upon disintegration, release infectious Mtb. Furthermore, hypoxic necrotic granulomas are associated with increased disease severity and provide a niche for drug-resistant Mtb. However, the host immune responses that promote the development of hypoxic TB granulomas are not well described. Using a necrotic Mtb mouse model, we show that loss of Mtb virulence factors, such as phenolic glycolipids, decreases the production of the proinflammatory cytokine IL-17 (also referred to as IL-17A). IL-17 …