Molecular Biology Of A Surface-Exposed Protein Family Of Bartonella Bacilliformis, 2017 University of Montana
Molecular Biology Of A Surface-Exposed Protein Family Of Bartonella Bacilliformis, Hannah Fay
Undergraduate Theses and Professional Papers
Bartonella bacilliformis is a gram negative alpha-proteobacterium native to the Andes of South America. Bartonella causes Carrion’s disease, a potentially life threatening disease transmitted by the sand fly. It has a mortality rate of 88% when untreated and 10% when treated. Diagnostics and control measures for the disease are underdeveloped and no vaccine is available. Recent outbreaks indicate that the range of the pathogen is increasing with nearly 1.7 million people in western South America at risk. Little is known about the epidemiology and pathogenesis of B. bacilliformis. Recent research done by UC San Diego found a paralogous ...
Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., 2016 George Washington University
Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors
Epidemiology and Biostatistics Faculty Publications
BACKGROUND: Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.
METHODS: Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.
RESULTS: Bordetella pertussis was detected in 53 of 4200 (1.3 ...
A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmfulalgal Bloom Toxins On The Bottlenose Dolphin, 2016 University of Southern Mississippi
A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmfulalgal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo
As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic ...
Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, 2016 George Washington University
Novel Mutation Of Interferon-Γ Receptor 1 Gene Presenting As Early Life Mycobacterial Bronchial Disease, Maria J. Gutierrez, Neelu Kaira, Alexandra Horwitz, Gustavo Nino
Pediatrics Faculty Publications
Mendelian susceptibility to mycobacterial diseases (MSMD) are a spectrum of inherited disorders characterized by localized or disseminated infections caused by atypical mycobacteria. Interferon-γ receptor 1 (IFNGR1) deficiency was the first identified genetic disorder recognized as MSMD. Mutations in the genes encoding IFNGR1 can be recessive or dominant and cause complete or partial receptor deficiency. We present the case of a 2½-year-old boy with a history of recurrent wheezing, diagnosed with endobronchial mycobacterial infection. Immunological workup revealed a homozygous nonsense mutation in the IFNGR1 gene, a novel mutation predicted in silico to cause complete IFNGR1 deficiency. This case demonstrates that (a ...
Structure And Bioactivity Of Neuropeptide F From The Human Parasites Schistosoma Mansoni And Schistosoma Japonicum, Judith E. Humphries, Michael J. Kimber, Yi-Wen Barton, Walter Hsu, Nikki J. Marks, Brett Greer, Pat Harriott, Aaron G. Maule, Timothy A. Day
Michael J. Kimber
The blood flukes Schistosoma mansoni and Schistosoma japonicuminflict immense suffering as agents of human schistosomiasis. Previous investigations have found the nervous systems of these worms contain abundant immunoreactivity to antisera targeting invertebrate neuropeptide Fs (NPFs) as well as structurally similar neuropeptides of the mammalian neuropeptide Y (NPY) family. Here, cDNAs encoding NPF in these worms were identified, and the mature neuropeptides from the two species differed by only a single amino acid. Both neuropeptides feature the characteristics common among NPFs; they are 36 amino acids long with a carboxyl-terminal Gly-Arg-X-Arg-Phe-amide and Tyr residues at positions 10 and 17 from the ...
The Case For Selection At Ccr5-Δ32, 2016 Broad Institute; Harvard Medical School
The Case For Selection At Ccr5-Δ32, Pardis Sabeti, Emily C. Walsh, Stephen F. Schaffner, Patrick Varilly, Ben Fry, Holli Hutcheson, Mike Cullen, Tarjei S. Mikkelsen, Jessica Roy, Nick Patterson, Richard Cooper, David Reich, David Altshuler, Stephen J. O'Brien, Eric S. Lander
The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Δ32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Δ32 arose within the past 1,000 y and rose to its present high frequency (5%–14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with ...
Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, 2016 National Cancer Institute at Frederick
Role Of Exonic Variation In Chemokine Receptor Genes On Aids: Ccrl2 F167y Association With Pneumocystis Pneumonia, Ping An, Rongling Li, Ji Ming Wang, Teizo Yoshimura, Munehisa Takahashi, Ram Samudralal, Stephen J. O'Brien, John Phair, James J. Goedert, Gregory D. Kirk, Jennifer L. Troyer, Efe Sezgin, Susan Buchbinder, Sharyne Donfield, George W. Nelson, Cheryl Winkler
Chromosome 3p21–22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 andCCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In ...
Regulatory Polymorphisms In The Cyclophilin A Gene, Ppia, Accelerate Progression To Aids, 2016 National Cancer Institute at Frederick
Regulatory Polymorphisms In The Cyclophilin A Gene, Ppia, Accelerate Progression To Aids, Ping An, Li Hua Wang, Holli Hutcheson-Dilks, George Nelson, Sharyne Donfield, James J. Goedert, Charles Rinaldo, Susan Buchbinder, Gregory D. Kirk, Stephen J. O'Brien, Cheryl Winkler
Human cyclophilin A, or CypA, encoded by the gene peptidyl prolyl isomerase A (PPIA), is incorporated into the HIV type 1 (HIV-1) virion and promotes HIV-1 infectivity by facilitating virus uncoating. We examined the effect of single nucleotide polymorphisms (SNPs) and haplotypes within the PPIA gene on HIV-1 infection and disease progression in five HIV-1 longitudinal history cohorts. Kaplan-Meier survival statistics and Cox proportional hazards model were used to assess time to AIDS outcomes. Among eight SNPs tested, two promoter SNPs (SNP3 and SNP4) in perfect linkage disequilibrium were associated with more rapid CD4+ T-cell loss (relative hazard = 3.7 ...
Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, 2016 National Cancer Institute at Frederick
Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, Ping An, Priya Duggal, Li Hua Wang, Stephen J. O'Brien, Sharyne Donfield, James J. Goedert, John Phair, Susan Buchbinder, Gregory D. Kirk, Cheryl Winkler
Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters ...
Genomically Intact Endogenous Feline Leukemia Viruses Of Recent Origin, 2016 National Cancer Institute at Frederick
Genomically Intact Endogenous Feline Leukemia Viruses Of Recent Origin, Alfred L. Roca, Jill Pecon-Slattery, Stephen J. O'Brien
We isolated and sequenced two complete endogenous feline leukemia viruses (enFeLVs), designated enFeLV-AGTT and enFeLV-GGAG. In enFeLV-AGTT, the open reading frames are reminiscent of a functioning FeLV genome, and the 5′ and 3′ long terminal repeat sequences are identical. Neither endogenous provirus is genetically fixed in cats but polymorphic, with 8.9 and 15.2% prevalence for enFeLV-AGTT and enFeLV-GGAG, respectively, among a survey of domestic cats. Neither provirus was found in the genomes of related species of the Felis genus, previously shown to harbor enFeLVs. The absence of mutational divergence, polymorphic incidence in cats, and absence in related species ...
Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, 2016 National Cancer Institute at Frederick
Genomic Organization, Sequence Divergence, And Recombination Of Feline Immunodeficiency Virus From Lions In The Wild, Jill Pecon-Slattery, Carrie L. Mccracken, Jennifer L. Troyer, Sue Vandewoude, Melody E. Roelke, Kerry Sondgeroth, Christiaan Winterbach, Stephen J. O'Brien
Feline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion.
In this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions ...
Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, 2016 National Cancer Institute at Frederick
Genetic Variants In Nuclear-Encoded Mitochondrial Genes Influence Aids Progression, Sher L. Hendrickson, J. A. Lautenberger, Leslie Wei Chinn, Michael Malasky, Lawrence Kingsley, James J. Goedert, Gregory D. Kirk, Edward Gomperts, Susan Buchbinder, Jennifer L. Troyer, Stephen J. O'Brien
Background: The human mitochondrial genome includes only 13 coding genes while nuclear-encoded genes account for 99% of proteins responsible for mitochondrial morphology, redox regulation, and energetics. Mitochondrial pathogenesis occurs in HIV patients and genetically, mitochondrial DNA haplogroups with presumed functional differences have been associated with differential AIDS progression.
Methodology/Principal Findings: Here we explore whether single nucleotide polymorphisms (SNPs) within 904 of the estimated 1,500 genes that specify nuclear-encoded mitochondrial proteins (NEMPs) influence AIDS progression among HIV-1 infected patients. We examined NEMPs for association with the rate of AIDS progression using genotypes generated by an Affymetrix 6.0 genotyping ...
Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, 2016 National Cancer Institute at Frederick
Genetic Characterization Of Feline Leukemia Virus From Florida Panthers, Meredith Brown, Mark W. Cunningham, Alfred L. Roca, Jennifer L. Troyer, Warren E. Johnson, Stephen J. O'Brien
From 2002 through 2005, an outbreak of feline leukemia virus (FeLV) occurred in Florida panthers (Puma concolor coryi). Clinical signs included lymphadenopathy, anemia, septicemia, and weight loss; 5 panthers died. Not associated with FeLV outcome were the genetic heritage of the panthers (pure Florida vs. Texas/Florida crosses) and co-infection with feline immunodeficiency virus. Genetic analysis of panther FeLV, designated FeLV-Pco, determined that the outbreak likely came from 1 cross-species transmission from a domestic cat. The FeLV-Pco virus was closely related to the domestic cat exogenous FeLV-A subgroup in lacking recombinant segments derived from endogenous FeLV. FeLV-Pco sequences were most ...
Evidence Of Natural Bluetongue Virus Infection Among African Carnivores, 2016 University of California - Davis
Evidence Of Natural Bluetongue Virus Infection Among African Carnivores, Kathleen A. Alexander, N. James Maclachlan, Pieter W. Kat, Carol House, Stephen J. O'Brien, Nicholas W. Lerche, Mary Sawyer, Laurence G. Frank, Kay Holekamp, Laura Smale, J. Weldon Mcnutt, M. Karen Laurenson, M. G. L. Mills, Bennie I. Osburn
Bluetongue is an International Office of Epizootics List A disease described as the century's most economically devastating affliction of sheep. Bluetongue (BLU) viruses were thought to infect only ruminants, shrews, and some rodents, but recently, inadvertent administration of BLU virus-contaminated vaccine resulted in mortality and abortion among domestic dogs. We present evidence of natural BLU virus infection among African carnivores that dramatically widens the spectrum of susceptible hosts. We hypothesize that such infection occurred after ingestion of meat and organs from BLU virus infected prey species. The effect of BLU virus on endangered carnivores such as the cheetah and ...
Effect Of A Single Amino Acid Change In Mhc Class I Molecules On The Rate Of Progression To Aids, 2016 National Cancer Institute at Frederick
Effect Of A Single Amino Acid Change In Mhc Class I Molecules On The Rate Of Progression To Aids, Xiaojiang Gao, George W. Nelson, Peter Karacki, Maureen P. Martin, John Phair, Richard A. Kaslow, James J. Goedert, Susan Buchbinder, Keith Hoots, David Vlahov, Stephen J. O'Brien, Mary Carrington
Background From studies of genetic polymorphisms and the rate of progression from human immunodeficiency virus type 1 (HIV-1) infection to the acquired immunodeficiency syndrome (AIDS), it appears that the strongest susceptibility is conferred by the major-histocompatibility-complex (MHC) class I type HLA-B*35,Cw*04 allele. However, cytotoxic T-lymphocyte responses have been observed against HIV-1 epitopes presented by HLA-B*3501, the most common HLA-B*35 subtype. We examined subtypes of HLA-B*35 in five cohorts and analyzed the relation of structural differences between HLA-B*35 subtypes to the risk of progression to AIDS. Methods Genotyping of HLA class I loci was ...
Common Genetic Variation And The Control Of Hiv-1 In Humans, 2016 Duke University
Common Genetic Variation And The Control Of Hiv-1 In Humans, Jacques Fellay, Dongliang Ge, Kevin V. Shianna, Sara Colombo, Bruno Ledergerber, Elizabeth T. Cirulli, Thomas J. Urban, Kunlin Zhang, Curtis Gumbs, Jason P. Smith, Antonella Castagna, Alessandro Cozzi-Lepri, Andrea De Luca, Philippa Easterbrook, Huldrych F. Gunthard, Simon Mallal, Cristina Mussini, Judith Dalmau, Javier Martinez-Picado, Jose M. Miro, Niels Obel, Steven M. Wolinsky, Jeremy J. Martinson, Roger Detels, Joseph Margolick, Lisa Jacobson, Patrick Descombes, Stylianos E. Antonarakis, Jacques S. Beckmann, Stephen J. O'Brien, Norman L. Letvin, Andrew J. Mcmichael, Barton F. Haynes, Mary Carrington, Sheng Feng, Amalio Telenti, David B. Goldstein
To extend the understanding of host genetic determinants of HIV-1 control, we performed a genome-wide association study in a cohort of 2,554 infected Caucasian subjects. The study was powered to detect common genetic variants explaining down to 1.3% of the variability in viral load at set point. We provide overwhelming confirmation of three associations previously reported in a genome-wide study and show further independent effects of both common and rare variants in the Major Histocompatibility Complex region (MHC). We also examined the polymorphisms reported in previous candidate gene studies and fail to support a role for any variant ...
A Population-Based Study To Investigate Host Genetic Factors Associated With Hepatitis B Infection And Pathogenesis In The Chinese Population, Zheng Zheng, Li Guan, Ping An, Shan Sun, Stephen J. O'Brien, Cheryl Winkler
Background Hepatitis B virus (HBV) infection is a significant public health problem that may lead to chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC). Approximately 30% of the world's population has been infected with HBV and approximately 350 million (5–6%) are persistent carriers. More than 120 million Chinese are infected with HBV. The role of host genetic factors and their interactions with environmental factors leading to chronic HBV infection and its complications are not well understood. We believe that a better understanding of these factors and interactions will lead to more effective diagnostic and therapeutic options. Methods/Design ...
A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, 2016 Ecole Polytechnique Federale de Lausanne - Switzerland; University of Lausanne - Switzerland; Eotvos Lorand University and the Hungarian Academy of Sciences - Budapest; Swiss Institute of Bioinformatics
A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, Istvan Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. Mclaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio Lopez-Galindez, Concepcion Casado, Andri Rauch, Huldrych F. Gunthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltan Kutalik, Todd M. Allen, Viktor Muller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay
HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10−12). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation for ...2.4>
The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, 2016 University of Massachusetts Medical School
The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista
GSBS Dissertations and Theses
While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late ...
Vaccination Strategies For Small Worlds, 2016 Ohio University - Main Campus
Vaccination Strategies For Small Worlds, Winfried Just, Hannah L. Callender
Annual Symposium on Biomathematics and Ecology: Education and Research
No abstract provided.