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Search Results: 1 - 10 of 153134 matches for " Guy H Palmer "
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Comparative genomics and transcriptomics of trait-gene association
Pierlé Sebastián,Dark Michael J,Dahmen Dani,Palmer Guy H
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-669
Abstract: Background The Order Rickettsiales includes important tick-borne pathogens, from Rickettsia rickettsii, which causes Rocky Mountain spotted fever, to Anaplasma marginale, the most prevalent vector-borne pathogen of cattle. Although most pathogens in this Order are transmitted by arthropod vectors, little is known about the microbial determinants of transmission. A. marginale provides unique tools for studying the determinants of transmission, with multiple strain sequences available that display distinct and reproducible transmission phenotypes. The closed core A. marginale genome suggests that any phenotypic differences are due to single nucleotide polymorphisms (SNPs). We combined DNA/RNA comparative genomic approaches using strains with different tick transmission phenotypes and identified genes that segregate with transmissibility. Results Comparison of seven strains with different transmission phenotypes generated a list of SNPs affecting 18 genes and nine promoters. Transcriptional analysis found two candidate genes downstream from promoter SNPs that were differentially transcribed. To corroborate the comparative genomics approach we used three RNA-seq platforms to analyze the transcriptomes from two A. marginale strains with different transmission phenotypes. RNA-seq analysis confirmed the comparative genomics data and found 10 additional genes whose transcription between strains with distinct transmission efficiencies was significantly different. Six regions of the genome that contained no annotation were found to be transcriptionally active, and two of these newly identified transcripts were differentially transcribed. Conclusions This approach identified 30 genes and two novel transcripts potentially involved in tick transmission. We describe the transcriptome of an obligate intracellular bacterium in depth, while employing massive parallel sequencing to dissect an important trait in bacterial pathogenesis.
Restriction of Francisella novicida Genetic Diversity during Infection of the Vector Midgut
Kathryn E. Reif ,Guy H. Palmer,David W. Crowder,Massaro W. Ueti,Susan M. Noh
PLOS Pathogens , 2014, DOI: doi/10.1371/journal.ppat.1004499
Abstract: The genetic diversity of pathogens, and interactions between genotypes, can strongly influence pathogen phenotypes such as transmissibility and virulence. For vector-borne pathogens, both mammalian hosts and arthropod vectors may limit pathogen genotypic diversity (number of unique genotypes circulating in an area) by preventing infection or transmission of particular genotypes. Mammalian hosts often act as “ecological filters” for pathogen diversity, where novel variants are frequently eliminated because of stochastic events or fitness costs. However, whether vectors can serve a similar role in limiting pathogen diversity is less clear. Here we show using Francisella novicida and a natural tick vector of Francisella spp. (Dermacentor andersoni), that the tick vector acted as a stronger ecological filter for pathogen diversity compared to the mammalian host. When both mice and ticks were exposed to mixtures of F. novicida genotypes, significantly fewer genotypes co-colonized ticks compared to mice. In both ticks and mice, increased genotypic diversity negatively affected the recovery of available genotypes. Competition among genotypes contributed to the reduction of diversity during infection of the tick midgut, as genotypes not recovered from tick midguts during mixed genotype infections were recovered from tick midguts during individual genotype infection. Mediated by stochastic and selective forces, pathogen genotype diversity was markedly reduced in the tick. We incorporated our experimental results into a model to demonstrate how vector population dynamics, especially vector-to-host ratio, strongly affected pathogen genotypic diversity in a population over time. Understanding pathogen genotypic population dynamics will aid in identification of the variables that most strongly affect pathogen transmission and disease ecology.
Identification of Rhipicephalus microplus Genes That Modulate the Infection Rate of the Rickettsia Anaplasma marginale
Ricardo F. Mercado-Curiel, María L. ávila-Ramírez, Guy H. Palmer, Kelly A. Brayton
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091062
Abstract: Arthropod vectors transmit a diversity of animal and human pathogens, ranging from RNA viruses to protozoal parasites. Chemotherapeutic control of pathogens has classically focused either on insecticides that kill the vector itself or antimicrobials for infected patients. The limitation of the former is that it targets both infected and uninfected vectors and selects for resistant populations while the latter requires prompt and accurate diagnosis. An alternative strategy is to target vector molecules that permit the pathogen to establish itself, replicate, and/or develop within the vector. Using the rickettsial pathogen Anaplasma marginale and its tropical tick vector, Rhipicephalus microplus, as a model, we tested whether silencing specific gene targets would affect tick infection rates (the % of fed ticks that are infected with the pathogen) and pathogen levels within infected ticks. Silencing of three R. microplus genes, CK187220, CV437619 and TC18492, significantly decreased the A. marginale infection rate in salivary glands, whereas gene silencing of TC22382, TC17129 and TC16059 significantly increased the infection rate in salivary glands. However in all cases of significant difference in the infection rate, the pathogen levels in the ticks that did become infected, were not significantly different. These results are consistent with the targeted genes affecting the pathogen at early steps in infection of the vector rather than in replication efficiency. Identifying vector genes and subsequent determination of the encoded functions are initial steps in discovery of new targets for inhibiting pathogen development and subsequent transmission.
Subdominant Antigens in Bacterial Vaccines: AM779 Is Subdominant in the Anaplasma marginale Outer Membrane Vaccine but Does Not Associate with Protective Immunity
Saleh M. Albarrak, Wendy C. Brown, Susan M. Noh, Kathryn E. Reif, Glen A. Scoles, Joshua E. Turse, Junzo Norimine, Massaro W. Ueti, Guy H. Palmer
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046372
Abstract: Identification of specific antigens responsible for the ability of complex immunogens to induce protection is a major goal in development of bacterial vaccines. Much of the investigation has focused on highly abundant and highly immunodominant outer membrane proteins. Recently however, genomic and proteomic approaches have facilitated identification of minor components of the bacterial outer membrane that have previously been missed or ignored in immunological analyses. Immunization with Anaplasma marginale outer membranes or a cross-linked surface complex induces protection against bacteremia, however the components responsible for protection within these complex immunogens are unknown. Using outer membrane protein AM779 as a model, we demonstrated that this highly conserved but minor component of the A. marginale surface was immunologically sub-dominant in the context of the outer membrane or surface complex vaccines. Immunologic sub-dominance could be overcome by targeted vaccination with AM779 for T lymphocyte responses but not for antibody responses, suggesting that both abundance and intrinsic immunogenicity determine relative dominance. Importantly, immunization with AM779 supports that once priming is achieved by specific targeting, recall upon infectious challenge is achieved. While immunization with AM779 alone was not sufficient to induce protection, the ability of targeted immunization to prime the immune response to highly conserved but low abundance proteins supports continued investigation into the role of sub-dominant antigens, individually and collectively, in vaccine development for A. marginale and related bacterial pathogens.
Attenuation of virulence in an apicomplexan hemoparasite results in reduced genome diversity at the population level
Audrey OT Lau, Ananth Kalyanaraman, Ignacio Echaide, Guy H Palmer, Russell Bock, Monica J Pedroni, Meenakshi Rameshkumar, Mariano B Ferreira, Taryn I Fletcher, Terry F McElwain
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-410
Abstract: Surprisingly, while single nucleotide polymorphisms in 14 genes distinguished all attenuated parasites from their virulent parental strains, all non-synonymous changes resulted in no deleterious amino acid modification that could consistently be associated with attenuation (or virulence) in this hemoparasite. Interestingly, however, attenuation significantly reduced the overall population's genome diversity with 81% of base pairs shared among attenuated strains, compared to only 60% of base pairs common among virulent parental parasites. There were significantly fewer genes that were unique to their geographical origins among the attenuated parasites, resulting in a simplified population structure among the attenuated strains.This simplified structure includes reduced diversity of the variant erythrocyte surface 1 (ves) multigene family repertoire among attenuated parasites when compared to virulent parental strains, possibly suggesting that overall variance in large protein families such as Variant Erythrocyte Surface Antigens has a critical role in expression of the virulence phenotype. In addition, the results suggest that virulence (or attenuation) mechanisms may not be shared among all populations of parasites at the gene level, but instead may reflect expansion or contraction of the population structure in response to shifting milieus.Pathogens adapt to maintain selective advantage in their environments. As few environments are themselves stable, pathogen adaptation is a dynamic and continuous process. This principle applies to virulence in which acquisition and loss of virulence is dynamic within a pathogen population, varying with host genetics, host immune status at the individual and population levels, and transmission efficiency. These shifts can be achieved through sexual reproduction where novel recombinations often lead to genome diversity [1]. However, for many multi-stage pathogens, this cannot occur during haploid life stages, and thus, they depend
Conservation in the face of diversity: multistrain analysis of an intracellular bacterium
Michael J Dark, David R Herndon, Lowell S Kappmeyer, Mikel P Gonzales, Elizabeth Nordeen, Guy H Palmer, Donald P Knowles, Kelly A Brayton
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-16
Abstract: These comparisons revealed that A. marginale has a closed-core genome with few highly plastic regions, which include the msp2 and msp3 genes, as well as the aaap locus. Comparison of the Florida and St. Maries genome sequences found that SNPs comprise 0.8% of the longer Florida genome, with 33.5% of the total SNPs between all five strains present in at least two strains and 3.0% of SNPs present in all strains except Florida. Comparison of genomes from three strains of Mycobacterium tuberculosis, Bacillus anthracis, and Nessieria meningiditis, as well as four Chlamydophila pneumoniae strains found that 98.8%–100% of SNPs are unique to each strain, suggesting A. marginale, with 76.0%, has an intermediate level of strain-specific SNPs. Comparison of genomes from other organisms revealed variation in diversity that did not segregate with the environmental niche the bacterium occupies, ranging from 0.00% to 8.00% of the larger pairwise-compared genome.Analysis of multiple A. marginale strains suggests intracellular bacteria have more variable SNP retention rates than previously reported, and may have closed-core genomes in response to the host organism environment and/or reductive evolution.While the recent boom in genome sequencing projects has provided a wealth of information about bacterial metabolism and evolution, we know little about interstrain variation. A firm understanding of the rates and sites of variation is useful in determining genotypic differences associated with phenotypic traits and in formulating control strategies for a number of pathogens. Further, knowledge about the pan-genome of organisms will aid in determining the core genomic requirements, as well as shed more light on events that occur in the various environmental niches bacteria occupy.Most studies of bacterial diversity to date have either utilized specific genomic loci [1,2] or have examined metagenomics of specific environmental niches [3,4]. While these types of studies help elucidate th
Sir Arnold Theiler and the discovery of anaplasmosis : a centennial perspective : tick-borne diseases
G.H. Palmer
Onderstepoort Journal of Veterinary Research , 2010, DOI: 10.4102/ojvr.v76i1.68
Abstract: Sir Arnold Theiler's research in 1908/09 led to the discovery of the first rickettsial pathogen, Anaplasma marginale, and set the stage for his development and implementation of an effective live vaccine based on a less virulent strain, A. marginale ss. centrale. His 1910 report, describing A. marginale, is among the classic monographs in infectious disease research, presenting not only observations in exacting detail but also highlighting the deductive reasoning leading to association of a new pathogen with a specific disease. With a centennial perspective and both conceptual frameworks and molecular tools unimaginable in Theiler's time, the significance of several observations in the original report - cyclic bacteremia, strain superinfection, and taxonomic position - is now clear and highlight the broad applicability of key principles of pathogen biology.
Gender Differences in Observed and Perceived Stress and Coping in Couples with a Depressed Partner  [PDF]
Barbara Gabriel, Guy Bodenmann, Steven R. H. Beach
Open Journal of Depression (OJD) , 2016, DOI: 10.4236/ojd.2016.52002
Abstract: Recent results show higher perceived stress and more dysfunctional coping in depressed individuals, and suggest that dyadic approaches focused on enhancing couples coping can be useful in treating depression. At the same time, a long tradition of research on couples with a depressed partner suggests potential differences between couples who are more or less maritally distressed, as well as due to the gender of depressed spouse. The present study investigates the association of gender and marital satisfaction with stress and coping patterns in couples with a depressed partner by comparing 4 groups (maritally distressed and non-distressed couples in which either the male or female partner was suffering from depression). Both questionnaires and observed marital interaction tasks were used to assess all constructs. Evidence was found for greater stress and stress generating coping practices for depressed individuals and more dysfunctional dyadic coping in maritally distressed couples. In addition, we identified gender-related patterns associated with depression and marital distress that may be important in working with couples. Coping oriented couples approaches may benefit from consideration of gender differences to maximize therapeutic effectiveness with a range of couples with a depressed partner.
Maintaining the Balance: Creative Practices in University-School Partnerships for Teacher Education  [PDF]
David Palmer
Creative Education (CE) , 2015, DOI: 10.4236/ce.2015.614153
Abstract: The professional placement is a central component of any teacher education program. In recent years, as teachers face a variety of new challenges that make substantial claims upon their time it is more than ever important that university-school partnerships include built-in components that will explicitly benefit teacher/mentors and the students in their schools. By including a combination of literature review and reports from experienced and innovative field operators, this paper has summarized a range of creative strategies that will enhance university partnerships with schools. For teacher education, it is vital that such partnerships continue to flourish, and it is hoped that this paper will contribute to that process.
Motivation for Learning: An Implicit Decision-Making Process  [PDF]
David Palmer
Creative Education (CE) , 2016, DOI: 10.4236/ce.2016.716229
Abstract: Motivation for learning is concerned with the activation of learning behaviors. It has previously been proposed that decision-making models might offer an explanation for how learning behaviors do become activated. The aim of this position paper was to investigate this proposal. The three main decision-making models were described and analyzed. There were problematic aspects common to all the models, so it was argued that some modifications were necessary, in the following way. It was proposed that there are many factors that can influence learning behaviors, and some of these would have a positive influence (e.g., high self-efficacy, high individual interest, supportive peers) whereas others would have a negative influence (e.g., very low self- efficacy, lack of individual interest, disruptive peers, hunger and fatigue). In one particular lesson, a student could experience a combination of positive and negative factors, so this implies that a decision-making event would be necessary in order to determine whether or not learning behaviors become activated. For several reasons, it was concluded that at least part of the process of comparing the factors and making a decision could occur at a subconscious level.
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