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  • 1
    Language: English
    In: Pediatrics, December 2012, Vol.130(6), pp.e1455-62
    Description: Fever without an apparent source is common in young children. Currently in the United States, serious bacterial infection is unusual. Our objective was to determine specific viruses that might be responsible. We enrolled children aged 2 to 36 months with temperature of 38°C or greater without an apparent source or with definite or probable bacterial infection being evaluated in the St Louis Children's Hospital Emergency Department and afebrile children having ambulatory surgery. Blood and nasopharyngeal swab samples were tested with an extensive battery of virus-specific polymerase chain reaction assays. One or more viruses were detected in 76% of 75 children with fever without an apparent source, 40% of 15 children with fever and a definite or probable bacterial infection, and 35% of 116 afebrile children (P 〈 .001). Four viruses (adenovirus, human herpesvirus 6, enterovirus, and parechovirus) were predominant, being detected in 57% of children with fever without a source, 13% of children with fever and definite or probable bacterial infection, and 7% of afebrile children (P 〈 .001). Thirty-four percent of 146 viral infections were detected only by polymerase chain reaction performed on blood. Fifty-one percent of children with viral infections and no evidence of bacterial infection were treated with antibiotics. Viral infections are frequent in children with fever without an apparent source. Testing of blood in addition to nasopharyngeal secretions expanded the range of viruses detected. Future studies should explore the utility of testing for the implicated viruses. Better recognition of viruses that cause undifferentiated fever in young children may help limit unnecessary antibiotic use.
    Keywords: Fever of Unknown Origin -- Virology ; Virus Diseases -- Diagnosis
    ISSN: 00314005
    E-ISSN: 1098-4275
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  • 2
    In: Nature, 2012, Vol.489(7415), p.250
    Description: The human body is colonized by a vast array of microbes, which form communities of bacteria, viruses and microbial eukaryotes that are specific to each anatomical environment. Every community must be studied as a whole because many organisms have never been cultured independently, and this poses formidable challenges. The advent of next-generation DNA sequencing has allowed more sophisticated analysis and sampling of these complex systems by culture-independent methods. These methods are revealing differences in community structure between anatomical sites, between individuals, and between healthy and diseased states, and are transforming our view of human biology.
    Keywords: Biodiversity ; Genomics -- Methods ; Metagenome -- Genetics;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 3
    In: Nature, 2013, Vol.500(7464), p.571
    Description: The dynamics of adaptation determine which mutations fix in a population, and hence how reproducible evolution will be. This is central to understanding the spectra of mutations recovered in the evolution of antibiotic resistance, the response of pathogens to immune selection, and the dynamics of cancer progression.In laboratory evolution experiments, demonstrably beneficial mutations are found repeatedly, but are often accompanied by other mutations with no obvious benefit. Here we use whole-genome whole-population sequencing to examine the dynamics of genome sequence evolution at high temporal resolution in 40 replicate Saccharomyces cerevisiae populations growing in rich medium for 1,000 generations. We find pervasive genetic hitchhiking: multiple mutations arise and move synchronously through the population as mutational 'cohorts'. Multiple clonal cohorts are often present simultaneously, competing with each other in the same population. Our results show that patterns of sequence evolution are driven by a balance between these chance effects of hitchhiking and interference, which increase stochastic variation in evolutionary outcomes, and the deterministic action of selection on individual mutations, which favours parallel evolutionary solutions in replicate populations. [PUBLICATION ]
    Keywords: Adaptation, Physiological–Genetics ; Cell Nucleus–Genetics ; Clone Cells–Cytology ; Clone Cells–Metabolism ; Evolution, Molecular–Genetics ; Genes, Fungal–Genetics ; Mutation–Classification ; Saccharomyces Cerevisiae–Cytology ; Saccharomyces Cerevisiae–Genetics ; Saccharomyces Cerevisiae–Growth & Development ; Saccharomyces Cerevisiae–Growth & Development ; Stochastic Processes–Growth & Development ; Time Factors–Growth & Development ; Mutation ; Yeast ; Hitchhiking ; Evolution ; Population ; Cloning ; Genomes;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 4
    In: Nature, 2012, Vol.493(7430), p.45
    Description: Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short insertions/deletions, and 1,051 structural variants. The average ratio of non- synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake.
    Keywords: Genetic Variation – Research ; Microbiota (Symbiotic Organisms) – Observations ; Microbiota (Symbiotic Organisms) – Genetic Aspects ; Genetic Markers – Identification and Classification;
    ISSN: 0028-0836
    E-ISSN: 14764687
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  • 5
    Language: English
    In: Annals of Epidemiology, May 2016, Vol.26(5), pp.301-305
    Description: The human microbiome is the community of microorganisms that live on and in the body. Currently, most applications of microbiome analysis derive from the perspective of discovery and characterization. The completion of the NIH Human Microbiome and the European MetaHIT projects will change the focus to studying the role of the microbiome on human health and disease. Recent developments in technology and bioinformatics have afforded an opportunity to explore more fully the importance of community structure, detection of pathogens, and community interactions. The current state of microbiome research in terms of effect size, power calculations, how stratification on community classes can increase this power, and the importance of study design and power in reproducibility is reviewed. Work is needed to characterize microbiome development, ecological stability, and variation. Development and implementation of variance stabilization techniques should replace rarefaction of data, which reduces study power, in future research. Epidemiologists have most of the tools necessary to explore the relationship between the microbiome and human health. Further development of tools for large-scale multivariate data sets will be helpful. Applying the methods of epidemiology will be critical in translating research results to preventive interventions and population health.
    Keywords: Microbiota ; Microbial Consortia ; Epidemiology ; Medicine ; Public Health
    ISSN: 1047-2797
    E-ISSN: 1873-2585
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  • 6
    Language: English
    In: Emerging Infectious Diseases, 01 November 2011, Vol.17(11), pp.2050-2052
    Description: Astroviruses cause diarrhea, but it is not known whether they circulate in human plasma. Astrovirus MLB2 was recently discovered in diarrhea samples from children. We detected MLB2 in the plasma of a febrile child, which suggests that MLB2 has broader tropism than expected and disease potential beyond the gastrointestinal tract.
    Keywords: Astroviruses ; Viruses ; Viremia ; Febrile ; Child ; Diarrhea ; Public Health
    ISSN: 1080-6040
    E-ISSN: 1080-6059
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  • 7
    Language: English
    In: JAMA pediatrics, January 2016, Vol.170(1), pp.11
    Keywords: Autoimmunity ; Autoantibodies -- Analysis ; Diabetes Mellitus, Type 1 -- Genetics ; Islets of Langerhans -- Immunology ; Probiotics -- Administration & Dosage
    ISSN: 21686203
    E-ISSN: 2168-6211
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  • 8
    Article
    Article
    Language: English
    In: Genome biology, 2011, Vol.12(5), pp.114
    Description: The first detailed temporal study of the human microbiome shows that individual body habitats exhibit surprising variation over time yet maintain distinguishable community structures.
    Keywords: Research Highlight ; Human Microbiome ; Microbial Communities ; Metagenomics ; Microbial Ecology;
    ISSN: 14656906
    E-ISSN: 1474-760X
    E-ISSN: 14656914
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  • 9
    Language: English
    In: Journal of Bacteriology, Dec, 2012, Vol.194(23-24), p.7016(2)
    Description: The DNA sequences of chromosomes I and II of Rhodobacter sphaeroides strain 2.4.1 have been revised, and the annotation of the entire genomic sequence, including both chromosomes and the five plasmids, has been updated. Errors in the originally published sequence have been corrected, and ~11% of the coding regions in the original sequence have been affected by the revised annotation.
    Keywords: Bacterial Genetics -- Research ; Photosynthetic Bacteria -- Genetic Aspects ; Plasmids -- Research
    ISSN: 0021-9193
    Source: Cengage Learning, Inc.
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  • 10
    In: Infection and Immunity, 2011, Vol. 79(7), p.2911
    Description: Ebp are endocarditis- and biofilm-associated pili of Enterococcus faecalis that are also important in experimental urinary tract infections (UTIs). Our analyses, using available genomes, found that the ebp locus is unique to enterococci. In E. faecalis, the ebp locus is very highly conserved and only 1/473 E. faecalis isolates tested lacked ebpABC, while only 1.2% had the bee pilus locus. No other pilus-encoding operon was identified in 55 available genomes, indicating that the vast majority of E. faecalis strains (unlike Enterococcus faecium and streptococci) have a single pilus locus. Surface expression studies showed that Ebp pili were produced in vitro by 91/91 brain heart infusion (BHI) plus serum-grown E. faecalis isolates and that strain OG1RF expressed pili at even higher levels in rat endocarditis vegetations. However, Ebp expression was restricted to 30 to 72% of E. faecalis cells, consistent with a bistability mode of expression. We also evaluated E. faecalis interactions with human platelets and found that growth of E. faecalis in BHI plus serum significantly enhanced adherence to human platelets and that sortase deletion mutants (the ΔsrtA, Δbps, and ΔbpsΔsrtA mutants) were markedly defective. Further studies identified that Ebp pili, but not the microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) Ace and Fss2, mediate adherence of E. faecalis to platelets. Taken together, our data show that the immunogenic (in human endocarditis patients) and commonly expressed Ebp pili, which are known to be important for experimental endocarditis, are highly conserved and mediate adherence to platelets, suggesting that Ebp pili may be a reasonable immunotherapeutic target for prevention or possibly treatment of endocarditis caused by this species. ; p. 2911-2920.
    Keywords: Blood Serum ; Enterococcus Faecalis ; Loci ; Humans ; Enterococcus Faecium ; Mutants ; Fimbriae ; Patients ; Urinary Tract Diseases ; Operon ; Apoidea ; Rats ; Endocarditis;
    ISSN: 0019-9567
    ISSN: 00199567
    E-ISSN: 10985522
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