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Search Results: 1 - 10 of 403969 matches for " Claire M Fraser "
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MICROBIAL GENOME SEQUENCING: PROSPECTS FOR DEVELOPMENT OF NOVEL VACCINES AND ANTI-MICROBIAL COMPOUNDS
Claire M. Fraser
The Scientific World Journal , 2002, DOI: 10.1100/tsw.2002.1
Abstract:
The complexity of simplicity
Scott N Peterson, Claire M Fraser
Genome Biology , 2001, DOI: 10.1186/gb-2001-2-2-comment2002
Abstract: Attempts to define life have touched nearly every scientific discipline and have been a long-standing subject in philosophy. Even when limited to the realm of biology, the definitions of life fall short of universal agreement and remain a widely debated subject. The practice of reductionism, whereby life is considered solely from the perspective of the genetic material, also generates controversy and complications. Many of these complications have been appreciated recently as a result of the large-scale application of whole-genome sequencing to microbes. The specific issue we discuss here is an attempt to define the minimum number of genes or functions necessary to support cellular life. The appeal of this subject lies largely in the fact that it represents a fundamental question in biology.We have approached the concept of a 'minimal genome' in a manner not unlike that taken by physicists interested in understanding the nature of the universe: we have relied on an underlying assumption or guiding force that states that a simple set of rules must exist. The difficulty lies in finding the proper way to strip away the outer layers of complexity in order to uncover what is truly general and therefore satisfactorily describes all things. It is our belief that some set of basic parameters and principles are common to all cellular life on this planet. On the surface, especially in the age of genomics, it would appear that we will indeed be able to draw inferences and define commonalities. The advent of whole-genome shotgun sequencing [1] has changed biology in ways that we will not fully appreciate for many years to come. Advances in functional genomics, structural genomics and computational biology have also contributed greatly to our ability to make 'sense' of the huge quantities of DNA sequence data being generated. As we begin to apply these methodologies to the question of the minimal genome, we are faced with new perspectives which emphasize that, like any good scie
Culture-Independent Evaluation of the Appendix and Rectum Microbiomes in Children with and without Appendicitis
Hope T. Jackson, Emmanuel F. Mongodin, Katherine P. Davenport, Claire M. Fraser, Anthony D. Sandler, Steven L. Zeichner
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095414
Abstract: Purpose The function of the appendix is largely unknown, but its microbiota likely contributes to function. Alterations in microbiota may contribute to appendicitis, but conventional culture studies have not yielded conclusive information. We conducted a pilot, culture-independent 16S rRNA-based microbiota study of paired appendix and rectal samples. Methods We collected appendix and rectal swabs from 21 children undergoing appendectomy, six with normal appendices and fifteen with appendicitis (nine perforated). After DNA extraction, we amplified and sequenced 16S rRNA genes and analyzed sequences using CLoVR. We identified organisms differing in relative abundance using ANOVA (p<0.05) by location (appendix vs. rectum), disease (appendicitis vs. normal), and disease severity (perforated vs. non-perforated). Results We identified 290 taxa in the study's samples. Three taxa were significantly increased in normal appendices vs. normal rectal samples: Fusibacter (p = 0.009), Selenomonas (p = 0.026), and Peptostreptococcus (p = 0.049). Five taxa were increased in abundance in normal vs. diseased appendices: Paenibacillaceae (p = 0.005), Acidobacteriaceae GP4 (p = 0.019), Pseudonocardinae (p = 0.019), Bergeyella (p = 0.019) and Rhizobium (p = 0.045). Twelve taxa were increased in the appendices of appendicitis patients vs. normal appendix: Peptostreptococcus (p = 0.0003), Bilophila (p = 0.0004), Bulleidia (p = 0.012), Fusobacterium (p = 0.018), Parvimonas (p = 0.003), Mogibacterium (p = 0.012), Aminobacterium (p = 0.019), Proteus (p = 0.028), Actinomycineae (p = 0.028), Anaerovorax (p = 0.041), Anaerofilum (p = 0.045), Porphyromonas (p = 0.010). Five taxa were increased in appendices in patients with perforated vs. nonperforated appendicitis: Bulleidia (p = 0.004), Fusibacter (p = 0.005), Prevotella (p = 0.021), Porphyromonas (p = 0.030), Dialister (p = 0.035). Three taxa were increased in rectum samples of patients with appendicitis compared to the normal patients: Bulleidia (p = 0.034), Dialister (p = 0.003), and Porphyromonas (p = 0.026). Conclusion Specific taxa are more abundant in normal appendices compared to the rectum, suggesting that a distinctive appendix microbiota exists. Taxa with altered abundance in diseased and severely diseased (perforated) samples may contribute to appendicitis pathogenesis, and may provide microbial signatures in the rectum useful for guiding both treatment and diagnosis of appendicitis.
Characterization of Clinically-Attenuated Burkholderia mallei by Whole Genome Sequencing: Candidate Strain for Exclusion from Select Agent Lists
Steven E. Schutzer, Linda R. K. Schlater, Catherine M. Ronning, David DeShazer, Benjamin J. Luft, John J. Dunn, Jacques Ravel, Claire M. Fraser-Liggett, William C. Nierman
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002058
Abstract: Background Burkholderia mallei is an understudied biothreat agent responsible for glanders which can be lethal in humans and animals. Research with this pathogen has been hampered in part by constraints of Select Agent regulations for safety reasons. Whole genomic sequencing (WGS) is an apt approach to characterize newly discovered or poorly understood microbial pathogens. Methodology/Principal Findings We performed WGS on a strain of B. mallei, SAVP1, previously pathogenic, that was experimentally infected in 6 equids (4 ponies, 1 mule, 1 donkey), natural hosts, for purposes of producing antibodies. Multiple high inocula were used in some cases. Unexpectedly SAVP1 appeared to be avirulent in the ponies and mule, and attenuated in the donkey, but induced antibodies. We determined the genome sequence of SAVP1 and compared it to a strain that was virulent in horses and a human. In comparison, this phenotypic avirulent SAVP1 strain was missing multiple genes including all the animal type III secretory system (T3SS) complex of genes demonstrated to be essential for virulence in mice and hamster models. The loss of these genes in the SAVP1 strain appears to be the consequence of a multiple gene deletion across insertion sequence (IS) elements in the B. mallei genome. Therefore, the strain by itself is unlikely to revert naturally to its virulent phenotype. There were other genes present in one strain and not the other and vice-versa. Conclusion/Significance The discovery that this strain of B. mallei was both avirulent in the natural host ponies, and did not possess T3SS associated genes may be fortuitous to advance biodefense research. The deleted virulence-essential T3SS is not likely to be re-acquired naturally. These findings may provide a basis for exclusion of SAVP1 from the Select Agent regulation or at least discussion of what else would be required for exclusion. This exclusion could accelerate research by investigators not possessing BSL-3 facilities and facilitate the production of reagents such as antibodies without the restraints of Select Agent regulation.
Impact of Oral Typhoid Vaccination on the Human Gut Microbiota and Correlations with S. Typhi-Specific Immunological Responses
Emiley A. Eloe-Fadrosh, Monica A. McArthur, Anna M. Seekatz, Elliott F. Drabek, David A. Rasko, Marcelo B. Sztein, Claire M. Fraser
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062026
Abstract: The resident microbial consortia of the human gastrointestinal tract play an integral role in modulating immune responses both locally and systemically. However, detailed information regarding the effector immune responses after vaccine administration in relation to the gastrointestinal microbiota is absent. In this study, the licensed oral live-attenuated typhoid vaccine Ty21a was administered in a clinical study to investigate whether oral immunization resulted in alterations of the microbiota and to identify whether a given microbiota composition, or subsets of the community, are associated with defined S. Typhi-specific immunological responses. The fecal microbiota composition and temporal dynamics were characterized using bacterial 16S rRNA pyrosequencing from individuals who were either immunized with the Ty21a typhoid vaccine (n = 13) or served as unvaccinated controls (n = 4). The analysis revealed considerable inter- and intra-individual variability, yet no discernible perturbations of the bacterial assemblage related to vaccine administration were observed. S. Typhi-specific cell mediated immune (CMI) responses were evaluated by measurement of intracellular cytokine production using multiparametric flow cytometry, and humoral responses were evaluated by measurement of serum anti-LPS IgA and IgG titers. Volunteers were categorized according to the kinetics and magnitude of their responses. While differences in microbial composition, diversity, or temporal stability were not observed among individuals able to mount a positive humoral response, individuals displaying multiphasic CMI responses harbored more diverse, complex communities. In line with this preliminary observation, over two hundred operational taxonomic units (OTUs) were found to differentiate multiphasic and late CMI responders, the vast majority of which classified within the order Clostridiales. These results provide an unprecedented view into the dramatic temporal heterogeneity of both the gut microbiota and host immune responses.
The disappearance of the progenitor of SN 2012aw in late-time imaging
M. Fraser
Physics , 2015, DOI: 10.1093/mnrasl/slv168
Abstract: We present new late-time near-infrared imaging of the site of the nearby core-collapse supernova SN 2012aw, confirming the disappearance of the point source identified by Fraser et al. (2012) and Van Dyk et al. (2012) as a candidate progenitor in both J and Ks filters. We re-measure the progenitor photometry, and find that both the J and Ks magnitudes of the source are consistent with those quoted in the literature. We also recover a marginal detection of the progenitor in H-band, for which we measure H=19.67+/-0.40 mag. Comparing the luminosity of the progenitor to stellar evolutionary models, SN 2012aw appears to have resulted from the explosion of a 12.5+/-1.5 Msun red supergiant.
Simultaneous Transcriptional Profiling of Bacteria and Their Host Cells
Michael S. Humphrys, Todd Creasy, Yezhou Sun, Amol C. Shetty, Marcus C. Chibucos, Elliott F. Drabek, Claire M. Fraser, Umar Farooq, Naomi Sengamalay, Sandy Ott, Huizhong Shou, Patrik M. Bavoil, Anup Mahurkar, Garry S. A. Myers
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080597
Abstract: We developed an RNA-Seq-based method to simultaneously capture prokaryotic and eukaryotic expression profiles of cells infected with intracellular bacteria. As proof of principle, this method was applied to Chlamydia trachomatis-infected epithelial cell monolayers in vitro, successfully obtaining transcriptomes of both C. trachomatis and the host cells at 1 and 24 hours post-infection. Chlamydiae are obligate intracellular bacterial pathogens that cause a range of mammalian diseases. In humans chlamydiae are responsible for the most common sexually transmitted bacterial infections and trachoma (infectious blindness). Disease arises by adverse host inflammatory reactions that induce tissue damage & scarring. However, little is known about the mechanisms underlying these outcomes. Chlamydia are genetically intractable as replication outside of the host cell is not yet possible and there are no practical tools for routine genetic manipulation, making genome-scale approaches critical. The early timeframe of infection is poorly understood and the host transcriptional response to chlamydial infection is not well defined. Our simultaneous RNA-Seq method was applied to a simplified in vitro model of chlamydial infection. We discovered a possible chlamydial strategy for early iron acquisition, putative immune dampening effects of chlamydial infection on the host cell, and present a hypothesis for Chlamydia-induced fibrotic scarring through runaway positive feedback loops. In general, simultaneous RNA-Seq helps to reveal the complex interplay between invading bacterial pathogens and their host mammalian cells and is immediately applicable to any bacteria/host cell interaction.
Differential Response of the Cynomolgus Macaque Gut Microbiota to Shigella Infection
Anna M. Seekatz, Aruna Panda, David A. Rasko, Franklin R. Toapanta, Emiley A. Eloe-Fadrosh, Abdul Q. Khan, Zhenqiu Liu, Steven T. Shipley, Louis J. DeTolla, Marcelo B. Sztein, Claire M. Fraser
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064212
Abstract: Little is known about the role of gut microbiota in response to live oral vaccines against enteric pathogens. We examined the effect of immunization with an oral live-attenuated Shigella dysenteriae 1 vaccine and challenge with wild-type S. dysenteriae 1 on the fecal microbiota of cynomolgus macaques using 16 S rRNA analysis of fecal samples. Multi-dimensional cluster analysis identified different bacterial community types within macaques from geographically distinct locations. The fecal microbiota of Mauritian macaques, observed to be genetically distinct, harbored a high-diversity community and responded differently to Shigella immunization, as well as challenge compared to the microbiota in non-Mauritian macaques. While both macaque populations exhibited anti-Shigella antibody responses, clinical shigellosis was observed only among non-Mauritian macaques. These studies highlight the importance of further investigation into the possible protective role of the microbiota against enteric pathogens and consideration of host genetic backgrounds in conducting vaccine studies.
Integrated Metagenomics/Metaproteomics Reveals Human Host-Microbiota Signatures of Crohn's Disease
Alison R. Erickson, Brandi L. Cantarel, Regina Lamendella, Youssef Darzi, Emmanuel F. Mongodin, Chongle Pan, Manesh Shah, Jonas Halfvarson, Curt Tysk, Bernard Henrissat, Jeroen Raes, Nathan C. Verberkmoes, Claire M. Fraser, Robert L. Hettich, Janet K. Jansson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0049138
Abstract: Crohn's disease (CD) is an inflammatory bowel disease of complex etiology, although dysbiosis of the gut microbiota has been implicated in chronic immune-mediated inflammation associated with CD. Here we combined shotgun metagenomic and metaproteomic approaches to identify potential functional signatures of CD in stool samples from six twin pairs that were either healthy, or that had CD in the ileum (ICD) or colon (CCD). Integration of these omics approaches revealed several genes, proteins, and pathways that primarily differentiated ICD from healthy subjects, including depletion of many proteins in ICD. In addition, the ICD phenotype was associated with alterations in bacterial carbohydrate metabolism, bacterial-host interactions, as well as human host-secreted enzymes. This eco-systems biology approach underscores the link between the gut microbiota and functional alterations in the pathophysiology of Crohn's disease and aids in identification of novel diagnostic targets and disease specific biomarkers.
Whole-Genome Analysis of Human Influenza A Virus Reveals Multiple Persistent Lineages and Reassortment among Recent H3N2 Viruses
Edward C. Holmes,Elodie Ghedin,Naomi Miller,Jill Taylor,Yiming Bao,Kirsten St George,Bryan T. Grenfell,Steven L. Salzberg,Claire M. Fraser,David J. Lipman,Jeffery K. Taubenberger
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.0030300
Abstract: Understanding the evolution of influenza A viruses in humans is important for surveillance and vaccine strain selection. We performed a phylogenetic analysis of 156 complete genomes of human H3N2 influenza A viruses collected between 1999 and 2004 from New York State, United States, and observed multiple co-circulating clades with different population frequencies. Strikingly, phylogenies inferred for individual gene segments revealed that multiple reassortment events had occurred among these clades, such that one clade of H3N2 viruses present at least since 2000 had provided the hemagglutinin gene for all those H3N2 viruses sampled after the 2002–2003 influenza season. This reassortment event was the likely progenitor of the antigenically variant influenza strains that caused the A/Fujian/411/2002-like epidemic of the 2003–2004 influenza season. However, despite sharing the same hemagglutinin, these phylogenetically distinct lineages of viruses continue to co-circulate in the same population. These data, derived from the first large-scale analysis of H3N2 viruses, convincingly demonstrate that multiple lineages can co-circulate, persist, and reassort in epidemiologically significant ways, and underscore the importance of genomic analyses for future influenza surveillance.
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