Life Sciences Commons^™

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

T-Cell Responses Targeting Hiv Nef Uniquely Correlate With Infected Cell Frequencies After Long-Term Antiretroviral Therapy., Allison S Thomas, Kimberley L Jones, Rajesh T Gandhi, Deborah K Mcmahon, Joshua C Cyktor, Dora Chan, Szu-Han Huang, Ronald Truong, Alberto Bosque, Amanda B Macedo, Colin Kovacs, Erika Benko, Joseph J Eron, Ronald J Bosch, Christina M Lalama, Samuel Simmens, Bruce D Walker, John W Mellors, R Brad Jones

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART), these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of …

Temporal Changes In Cortical And Hippocampal Expression Of Genes Important For Brain Glucose Metabolism Following Controlled Cortical Impact Injury In Mice, June Zhou, Mark Burns, Linda Huynh, Sonia Villapol, Daniel D. Taub, Juan M. Saavedra, Marc R. Blackman

Pharmacology and Physiology Faculty Publications

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. …

Anti-Herv-K (Hml-2) Capsid Antibody Responses In Hiv Elite Controllers., Miguel De Mulder, Devi Sengupta, Steven G Deeks, Jeffrey N Martin, Christopher D Pilcher, Frederick M Hecht, Jonah B Sacha, Douglas F Nixon, Henri-Alexandre Michaud

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Human endogenous retroviruses (HERVs) comprise approximately 8% of the human genome and while the majority are transcriptionally silent, the most recently integrated HERV, HERV-K (HML-2), remains active. During HIV infection, HERV-K (HML-2) specific mRNA transcripts and viral proteins can be detected. In this study, we aimed to understand the antibody response against HERV-K (HML-2) Gag in the context of HIV-1 infection.

Results

We developed an ELISA assay using either recombinant protein or 164 redundant “15mer” HERV-K (HML-2) Gag peptides to test sera for antibody reactivity. We identified a total of eight potential HERV-K (HML-2) Gag immunogenic domains: two on …

Overexpressed Somatic Alleles Are Enriched In Functional Elements In Breast Cancer., Paula Restrepo, Mercedeh Movassagh, Nawaf Alomran, Christian Miller, Muzi Li, Chris Trenkov, Yulian Manchev, Sonali Bahl, Stephanie Warnken, Liam Spurr, Tatiyana Apanasovich, Keith Crandall, Nathan Edwards, Anelia Horvath

Pharmacology and Physiology Faculty Publications

Asymmetric allele content in the transcriptome can be indicative of functional and selective features of the underlying genetic variants. Yet, imbalanced alleles, especially from diploid genome regions, are poorly explored in cancer. Here we systematically quantify and integrate the variant allele fraction from corresponding RNA and DNA sequence data from patients with breast cancer acquired through The Cancer Genome Atlas (TCGA). We test for correlation between allele prevalence and functionality in known cancer-implicated genes from the Cancer Gene Census (CGC). We document significant allele-preferential expression of functional variants in CGC genes and across the entire dataset. Notably, we find frequent …

Parasite Microbiome Project: Systematic Investigation Of Microbiome Dynamics Within And Across Parasite-Host Interactions., Nolwenn M Dheilly, Daniel Bolnick, Seth Bordenstein, Paul J Brindley, Cédric Figuères, Edward C Holmes, Joaquín Martínez Martínez, Anna J Phillips, Robert Poulin, Karyna Rosario

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Understanding how microbiomes affect host resistance, parasite virulence, and parasite-associated diseases requires a collaborative effort between parasitologists, microbial ecologists, virologists, and immunologists. We hereby propose the Parasite Microbiome Project to bring together researchers with complementary expertise and to study the role of microbes in host-parasite interactions. Data from the Parasite Microbiome Project will help identify the mechanisms driving microbiome variation in parasites and infected hosts and how that variation is associated with the ecology and evolution of parasites and their disease outcomes. This is a call to arms to prevent fragmented research endeavors, encourage best practices in experimental approaches, and …

Helminth Infection-Induced Malignancy., Paul J Brindley, Alex Loukas

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infectious diseases cause more than 20% of cancers in the developing world [1]. About a dozen pathogens including Epstein-Barr virus and human T cell lymphocytotropic virus 1 are among the well-known examples. In addition, infection with several trematodes, which are eukaryotes, can cause malignancy. The International Agency for Research on Cancer categorizes infection with the fish-borne trematodes Opisthorchis viverrini and Clonorchis sinensis and the blood fluke Schistosoma haematobium as Group 1 biological carcinogens [2]. In addition to parasitism directly damaging development, health, and prosperity of infected populations, infection with these helminths leads to cholangiocarcinoma (CCA) (bile duct cancer) and squamous …

Alternative Splicing Promotes Tumour Aggressiveness And Drug Resistance In African American Prostate Cancer., Bi-Dar Wang, Kristin Ceniccola, Sujin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A Garcia-Blanco, Steven R Patierno, Norman H Lee

Pharmacology and Physiology Faculty Publications

linical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants. Ectopic overexpression of the newly cloned AA-enriched variant, PIK3CD-S, in EA PCa cell lines enhances AKT/mTOR signalling and increases proliferative …

Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, …

A Novel Micro Cold Atmospheric Plasma Device For Glioblastoma Both In Vitro And In Vivo., Zhitong Chen, Hayk Simonyan, Xiaoqian Cheng, Eda Gjika, Li Lin, Jerome Canady, Jonathan H Sherman, Colin Young, Michael Keidar

Pharmacology and Physiology Faculty Publications

: Cold atmospheric plasma (CAP) treatment is a rapidly expanding and emerging technology for cancer treatment. Direct CAP jet irradiation is limited to the skin and it can also be invoked as a supplement therapy during surgery as it only causes cell death in the upper three to five cell layers. However, the current cannulas from which the plasma emanates are too large for intracranial applications. To enhance efficiency and expand the applicability of the CAP method for brain tumors and reduce the gas flow rate and size of the plasma jet, a novel micro-sized CAP device (µCAP) was developed …

Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, Ladeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify …

Safety And Immunogenicity Of The Na-Gst-1 Hookworm Vaccine In Brazilian And American Adults., David J Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) plays a role in the digestion of host hemoglobin by adult N. americanus hookworms. Vaccination of laboratory animals with recombinant Na-GST-1 is associated with significant protection from challenge infection. Recombinant Na-GST-1 was expressed in Pichia pastoris and adsorbed to aluminum hydroxide adjuvant (Alhydrogel) according to current Good Manufacturing Practice. Two Phase 1 trials were conducted in 142 healthy adult volunteers in the United States and Brazil, first in hookworm-naïve individuals and then in residents of a N. americanus endemic area in Brazil. Volunteers received one of three doses of recombinant …

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Enzyme-Dependent Fluorescence Recovery Of Nadh After Photobleaching To Assess Dehydrogenase Activity Of Isolated Perfused Hearts., Angel Moreno, Sarah Kuzmiak-Glancy, Rafael Jaimes, Matthew W Kay

Pharmacology and Physiology Faculty Publications

Reduction of NAD(+) by dehydrogenase enzymes to form NADH is a key component of cellular metabolism. In cellular preparations and isolated mitochondria suspensions, enzyme-dependent fluorescence recovery after photobleaching (ED-FRAP) of NADH has been shown to be an effective approach for measuring the rate of NADH production to assess dehydrogenase enzyme activity. Our objective was to demonstrate how dehydrogenase activity could be assessed within the myocardium of perfused hearts using NADH ED-FRAP. This was accomplished using a combination of high intensity UV pulses to photobleach epicardial NADH. Replenishment of epicardial NADH fluorescence was then imaged using low intensity UV illumination. NADH …

Proteome Dynamics During Postnatal Mouse Corpus Callosum Development., Alexander I Son, Xiaoqin Fu, Fumikazu Suto, Judy S Liu, Kazue Hashimoto-Torii, Masaaki Torii

Pharmacology and Physiology Faculty Publications

Formation of cortical connections requires the precise coordination of numerous discrete phases. This is particularly significant with regard to the corpus callosum, whose development undergoes several dynamic stages including the crossing of axon projections, elimination of exuberant projections, and myelination of established tracts. To comprehensively characterize the molecular events in this dynamic process, we set to determine the distinct temporal expression of proteins regulating the formation of the corpus callosum and their respective developmental functions. Mass spectrometry-based proteomic profiling was performed on early postnatal mouse corpus callosi, for which limited evidence has been obtained previously, using stable isotope of labeled …

A Role Of Central Nell2 In The Regulation Of Feeding Behavior In Rats., Jin Kwon Jeong, Jae Geun Kim, Han Rae Kim, Tae Hwan Lee, Jeong Woo Park, Byung Ju Lee

Pharmacology and Physiology Faculty Publications

A brain-enriched secreting signal peptide, NELL2, has been suggested to play multiple roles in the development, survival, and activity of neurons in mammal. We investigated here a possible involvement of central NELL2 in regulating feeding behavior and metabolism. In situ hybridization and an immunohistochemical approach were used to determine expression of NELL2 as well as its colocalization with proopiomelanocortin (POMC) and neuropeptide Y (NPY) in the rat hypothalamus. To investigate the effect of NELL2 on feeding behavior, 2 nmole of antisense NELL2 oligodeoxynucleotide was administered into the lateral ventricle of adult male rat brains for 6 consecutive days, and changes …

Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Eggs produced by the mature female parasite are responsible for the pathogenesis and transmission of schistosomiasis. Female schistosomes rely on a unique male-induced strategy to accomplish reproductive development, a process that is incompletely understood. Here we map detailed transcriptomic profiles of male and female Schistosoma japonicum across eight time points throughout the sexual developmental process from pairing to maturation. The dynamic gene expression pattern data reveal clear sex-related characteristics, indicative of an unambiguous functional division between males and females during their interplay. Cluster analysis, in situ hybridization and RNAi assays indicate that males likely use biogenic amine neurotransmitters through the …

Chemogenetic Stimulation Of The Hypoglossal Neurons Improves Upper Airway Patency, Thomas Curado, Kenneth Fishbein, Huy Pho, Michael Brennick, Olga Dergacheva, David Mendelowitz, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstruction during sleep. OSA leads to high cardiovascular morbidity and mortality. The pathogenesis of OSA has been linked to a defect in neuromuscular control of the pharynx. There is no effective pharmacotherapy for OSA. The objective of this study was to determine whether upper airway patency can be improved using chemogenetic approach by deploying designer receptors exclusively activated by designer drug (DREADD) in the hypoglossal motorneurons. DREADD (rAAV5-hSyn-hM3(Gq)-mCherry) and control virus (rAAV5-hSyn-EGFP) were stereotactically administered to the hypoglossal nucleus of C57BL/6J mice. In 6–8 weeks genioglossus EMG and dynamic MRI …

Oxidative Stress-Driven Parvalbumin Interneuron Impairment As A Common Mechanism In Models Of Schizophrenia, P Steullet, J Cabungcal, J Coyle, M Didriksen, K Gill, Anthony-Samuel Lamantia, +Several Additional Authors

Pharmacology and Physiology Faculty Publications

Parvalbumin inhibitory interneurons (PVIs) are crucial for maintaining proper excitatory/inhibitory balance and high-frequency neuronal synchronization. Their activity supports critical developmental trajectories, sensory and cognitive processing, and social behavior. Despite heterogeneity in the etiology across schizophrenia and autism spectrum disorder, PVI circuits are altered in these psychiatric disorders. Identifying mechanism(s) underlying PVI deficits is essential to establish treatments targeting in particular cognition. On the basis of published and new data, we propose oxidative stress as a common pathological mechanism leading to PVI impairment in schizophrenia and some forms of autism. A series of animal models carrying genetic and/or environmental risks relevant …

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these …

Diagnosis Of Lchad/Tfp Deficiency In An At Risk Newborn Using Umbilical Cord Blood Acylcarnitine Analysis, Donna Raval, Kristina Cusmano-Ozog, Omar Ayyub, Callie Jenevein, Laura Kofman, Brendan Lanpher, Natalie Hauser, Debra Regier

Pathology Faculty Publications

Trifunctional protein deficiency/Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD/TFP) deficiency is a disorder of fatty acid oxidation and ketogenesis. Severe neonatal lactic acidosis, cardiomyopathy, and hepatic dysfunction are caused by the accumulation of toxic long-chain acylcarnitines. The feasibility of umbilical cord blood use in screening for acylcarnitine analysis and free carnitine has been hypothesized but not reported in LCHAD/TFP neonates.

We present a 4 week old female who was at risk of inheriting LCHAD/TFP deficiency and was diagnosed at the time of delivery using umbilical cord blood. Umbilical cord blood was collected at delivery and sent for acylcarnitine analysis. Treatment was started …

Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Recent reports suggest that Opisthorchis viverrini serves as a reservoir of Helicobacter and implicate Helicobacter in pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA). Here, 553 age-sex matched cases and controls, 293 and 260 positive and negative for liver fluke O. viverrini eggs, of residents in Northeastern Thailand were investigated for associations among infection with liver fluke, Helicobacter and hepatobiliary fibrosis. The prevalence of H. pylori infection was higher in O. viverrini-infected than uninfected participants. H. pylori bacterial load correlated positively with intensity of O. viverrini infection, and participants with opisthorchiasis exhibited higher frequency of virulent cagA-positive H. pylori than those free of …

Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are …

Genetic Targeting In Cerebellar Purkinje Cells: An Update., Anna Sługocka, Jan Wiaderkiewicz, Jaroslaw J Barski

Pharmacology and Physiology Faculty Publications

Since the last review paper published in Cerebellum in 2002 [1], there has been a substantial increase in the number of experiments utilizing transgenic manipulations in murine cerebellar Purkinje cells. Most of these approaches were made possible with the use of the Cre/loxP methodology and pcp2/L7 based Cre recombinase expressing transgenic mouse strains. This review aims to summarize all studies which used Purkinje cell specific transgenesis since the first use of mouse strain with Purkinje cell specific Cre expression in 2002.

Parasite Infection, Carcinogenesis And Human Malignancy., Hoang Van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in …

Yeast Help Identify Cytopathic Factors Of Zika Virus, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Accumulating evidence implicates Zika virus (ZIKV) in pathogenesis of microcephaly in newborns and Guillain-Barré syndrome in adults. However, it remains unclear which viral proteins are responsible for these effects and what are the underlying mechanisms of their pathogenic activity. A recent paper by Drs. Zhao and Gallo, and their colleagues at University of Maryland in Baltimore used fission yeast for genome-wide analysis of ZIKV proteins. They demonstrated cytopathogenic activity for seven ZIKV proteins, anaC, C, prM, M, E, NS2B and NS4A. This activity was shown to be dependent on oxidative stress, and for NS4A they demonstrated involvement of the TOR …

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed …

Identification Of Candidate Infection Genes From The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Jonathan Vadnal, Ramesh Ratnappan, Melissa Keaney, Eric Kenney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Despite important progress in the field of innate immunity, our understanding of host immune responses to parasitic nematode infections lags behind that of responses to microbes. A limiting factor has been the obligate requirement for a vertebrate host which has hindered investigation of the parasitic nematode infective process. The nematode parasite Heterorhabditis bacteriophora offers great potential as a model to genetically dissect the process of infection. With its mutualistic Photorhabdus luminescens bacteria, H. bacteriophora invades multiple species of insects, which it kills and exploits as a food source for the development of several nematode generations. The ability to culture …

Uncorrelated Neural Firing In Mouse Visual Cortex During Spontaneous Retinal Waves, Matthew Colonnese, Jing Shen, Yasunobu Murata

Pharmacology and Physiology Faculty Publications

Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity …

Genomes Of Fasciola Hepatica From The Americas Reveal Colonization With Neorickettsia Endobacteria Related To The Agents Of Potomac Horse And Human Sennetsu Fevers., Samantha N Mcnulty, Jose F Tort, Gabriel Rinaldi, Bruce A Rosa, Victoria H. Mann, Patricia S. Latham, Paul J. Brindley, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Food borne trematodes (FBTs) are an assemblage of platyhelminth parasites transmitted through the food chain, four of which are recognized as neglected tropical diseases (NTDs). Fascioliasis stands out among the other NTDs due to its broad and significant impact on both human and animal health, as Fasciola sp., are also considered major pathogens of domesticated ruminants. Here we present a reference genome sequence of the common liver fluke, Fasciola hepatica isolated from sheep, complementing previously reported isolate from cattle. A total of 14,642 genes were predicted from the 1.14 GB genome of the liver fluke. Comparative genomics indicated that F. …