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  • 1
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 09 June 2015, Vol.112(23), pp.7231-6
    Description: The response to an innate immune challenge is conditioned by the time of day, but the molecular basis for this remains unclear. In myeloid cells, there is a temporal regulation to induction by lipopolysaccharide (LPS) of the proinflammatory microRNA miR-155 that correlates inversely with levels of BMAL1. BMAL1 in the myeloid lineage inhibits activation of NF-κB and miR-155 induction and protects mice from LPS-induced sepsis. Bmal1 has two miR-155-binding sites in its 3'-UTR, and, in response to LPS, miR-155 binds to these two target sites, leading to suppression of Bmal1 mRNA and protein in mice and humans. miR-155 deletion perturbs circadian function, gives rise to a shorter circadian day, and ablates the circadian effect on cytokine responses to LPS. Thus, the molecular clock controls miR-155 induction that can repress BMAL1 directly. This leads to an innate immune response that is variably responsive to challenges across the circadian day.
    Keywords: Bmal1 ; Circadian Clock ; Inflammation ; Mir-155 ; Sepsis ; Circadian Rhythm ; Immunity, Innate ; Arntl Transcription Factors -- Physiology ; Macrophages -- Immunology ; Micrornas -- Physiology
    ISSN: 00278424
    E-ISSN: 1091-6490
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  • 2
    Language: English
    Description: Functional divergence is the process by which new genes and functions originate through the modification of existing ones. Both genetic and environmental factors influence the evolution of new functions, including gene duplication or changes in the ecological requirements of an organism. Novel functions emerge at the expense of ancestral ones and are generally accompanied by changes in the selective forces at constrained protein regions. We present software capable of analyzing whole proteomes, identifying putative amino acid replacements leading to functional change in each protein and performing statistical tests on all tabulated data. We apply this method to 750 complete bacterial proteomes to identify high-level patterns of functional divergence and link these patterns to ecological adaptations. Proteome-wide analyses of functional divergence in bacteria with different ecologies reveal a separation between proteins involved in information processing (Ribosome biogenesis etc.) and those which are dependent on the environment (energy metabolism, defense etc.). We show that the evolution of pathogenic and symbiotic bacteria is constrained by their association with the host, and also identify unusual events of functional divergence even in well-studied bacteria such as Escherichia coli. We present a description of the roles of phylogeny and ecology in functional divergence at the level of entire proteomes in bacteria.
    Keywords: Detecting Positive Selection ; Amino-Acid Sites ; Bartonella-Bacilliformis ; Escherichia Coli ; Genome Sequence ; Molecular Adaptation ; Statistical Methods ; Maximum Likelihood ; Gene Duplication ; Cog Database
    ISSN: 1932-6203
    ISSN: 22563391
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  • 3
    Language: English
    In: Molecular Microbiology, Sept, 2012, Vol.85, p.1072(18)
    Keywords: Transcription (Genetics) -- Genetic Aspects ; Transcription (Genetics) -- Analysis ; Bacterial Genetics -- Genetic Aspects ; Bacterial Genetics -- Analysis ; Preventive Medicine -- Analysis ; Dna Binding Proteins -- Genetic Aspects ; Dna Binding Proteins -- Analysis ; Genes -- Genetic Aspects ; Genes -- Analysis ; Rna -- Genetic Aspects ; Rna -- Analysis ; Salmonella -- Analysis
    ISSN: 0950-382X
    Source: Cengage Learning, Inc.
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  • 4
    Language: English
    In: Molecular Microbiology, Sept, 2012, Vol.85, p.1072(18)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2958.2012.08162.x/abstract Byline: Shane C. Dillon(1), Elena Espinosa(3), Karsten Hokamp(2), David W. Ussery(4), Josep Casadesus(3), Charles J. Dorman(1) Summary We report the first investigation of the binding of the Salmonella enterica LeuO LysR-type transcription regulator to its genomic targets in vivo. Chromatin-immunoprecipitation-on-chip identified 178 LeuO binding sites on the chromosome of S. enterica serovar Typhimurium strain SL1344. These sites were distributed across both the core and the horizontally acquired genome, and included housekeeping genes and genes known to contribute to virulence. Sixty-eight LeuO targets were co-bound by the global repressor protein, H-NS. Thus, while LeuO may function as an H-NS antagonist, these functions are unlikely to involve displacement of H-NS. RNA polymerase bound 173 of the 178 LeuO targets, consistent with LeuO being a transcription regulator. Thus, LeuO targets two classes of genes, those that are bound by H-NS and those that are not bound by H-NS. LeuO binding site analysis revealed a logo conforming to the TN.sub.11A motif common to LysR-type transcription factors. It differed in some details from a motif that we composed for Escherichia coli LeuO binding sites; 1263 and 1094 LeuO binding site locations were predicted in the S. Typhimurium SL1344 and E. coli MG1655 genomes respectively. Despite differences in motif composition, many LeuO target genes were common to both species. Thus, LeuO is likely to be a more important global regulator than previously suspected. Author Affiliation: (1)Department of Microbiology, School of Genetics and Microbiology, Moyne Institute of Preventive Medicine (2)Department of Genetics, School of Genetics and Microbiology, Smurfit Institute, Trinity College Dublin, Dublin 2, Ireland (3)Departamento de Genetica, Facultad de Biologia, Universidad de Sevilla, Apartado 1095, Seville 41080, Spain (4)Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark Correspondence: (*) E-mail cjdorman@tcd.ie; Tel. (+353) 1 8962013; Fax (+353) 1 6799294. Accepted 29 June, 2012. Supporting information: Additional Supporting Information may be found in the online version of this article
    Keywords: Transcription (Genetics) -- Genetic Aspects ; Transcription (Genetics) -- Analysis ; Bacterial Genetics -- Genetic Aspects ; Bacterial Genetics -- Analysis ; Preventive Medicine -- Analysis ; Dna Binding Proteins -- Genetic Aspects ; Dna Binding Proteins -- Analysis ; Genes -- Genetic Aspects ; Genes -- Analysis ; Rna -- Genetic Aspects ; Rna -- Analysis ; Salmonella -- Analysis
    ISSN: 0950-382X
    Source: Cengage Learning, Inc.
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  • 5
    Language: English
    In: Journal of bacteriology, April 2015, Vol.197(8), pp.1492-506
    Description: The PhoPR two-component signal transduction system controls one of three responses activated by Bacillus subtilis to adapt to phosphate-limiting conditions (PHO response). The response involves the production of enzymes and transporters that scavenge for phosphate in the environment and assimilate it into the cell. However, in B. subtilis and some other Firmicutes bacteria, cell wall metabolism is also part of the PHO response due to the high phosphate content of the teichoic acids attached either to peptidoglycan (wall teichoic acid) or to the cytoplasmic membrane (lipoteichoic acid). Prompted by our observation that the phosphorylated WalR (WalR∼P) response regulator binds to more chromosomal loci than are revealed by transcriptome analysis, we established the PhoP∼P bindome in phosphate-limited cells. Here, we show that PhoP∼P binds to the chromosome at 25 loci: 12 are within the promoters of previously identified PhoPR regulon genes, while 13 are newly identified. We extend the role of PhoPR in cell wall metabolism showing that PhoP∼P binds to the promoters of four cell wall-associated operons (ggaAB, yqgS, wapA, and dacA), although none show PhoPR-dependent expression under the conditions of this study. We also show that positive autoregulation of phoPR expression and full induction of the PHO response upon phosphate limitation require PhoP∼P binding to the 3' end of the phoPR operon. The PhoPR two-component system controls one of three responses mounted by B. subtilis to adapt to phosphate limitation (PHO response). Here, establishment of the phosphorylated PhoP (PhoP∼P) bindome enhances our understanding of the PHO response in two important ways. First, PhoPR plays a more extensive role in adaptation to phosphate-limiting conditions than was deduced from transcriptome analyses. Among 13 newly identified binding sites, 4 are cell wall associated (ggaAB, yqgS, wapA, and dacA), revealing that PhoPR has an extended involvement in cell wall metabolism. Second, amplification of the PHO response must occur by a novel mechanism since positive autoregulation of phoPR expression requires PhoP∼P binding to the 3' end of the operon.
    Keywords: Genome, Bacterial ; Bacillus Subtilis -- Metabolism ; Bacterial Proteins -- Metabolism ; Chromosomes, Bacterial -- Metabolism ; DNA, Bacterial -- Metabolism ; Phosphates -- Metabolism
    ISSN: 00219193
    E-ISSN: 1098-5530
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  • 6
    Language: English
    In: PLoS ONE, 01 January 2017, Vol.12(5), p.e0177977
    Description: The thalamus or "inner chamber" of the brain is divided into ~30 discrete nuclei, with highly specific patterns of afferent and efferent connectivity. To identify genes that may direct these patterns of connectivity, we used two strategies. First, we used a bioinformatics pipeline to survey...
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: Methods in molecular biology (Clifton, N.J.), 2015, Vol.1326, pp.177-91
    Description: Computational analyses of biological data are becoming increasingly powerful, and researchers intending on carrying out their own analyses can often choose from a wide array of tools and resources. However, their application might be obstructed by the wide variety of different data formats that are in use, from standard, commonly used formats to output files from high-throughput analysis platforms. The latter are often too large to be opened, viewed, or edited by standard programs, potentially leading to a bottleneck in the analysis. Perl one-liners provide a simple solution to quickly reformat, filter, and merge data sets in preparation for downstream analyses. This chapter presents example code that can be easily adjusted to meet individual requirements. An online version is available at http://bioinf.gen.tcd.ie/pol.
    Keywords: Bioinformatics ; Data Formatting ; Data Merging ; One-Liners ; Perl ; Programming ; Datasets As Topic
    ISSN: 10643745
    E-ISSN: 1940-6029
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 8
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States of America, 2018, Vol. 115(11), pp. E2614-E2623
    Description: Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S. Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only similar to 1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella. We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S. Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.
    Keywords: Salmonella ; Noncoding Genome ; Transcriptomics ; Evolution Of Virulence ; Host Adaptation ; Medical And Health Sciences ; Clinical Medicine ; Infectious Medicine ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Infektionsmedicin
    ISSN: 0027-8424
    E-ISSN: 10916490
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  • 9
    Language: English
    In: Neuron, 19 March 2014, Vol.81(6), pp.1297-1311
    Description: Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in . Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct -dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of , and induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons. Zarin et al. show that the transcription factors Eve, Zfh1, and Grain induce the expression of overlapping sets of guidance receptors and adhesion molecules in individual motoneurons constituting a network of regulators required for robust expression of those guidance molecules.
    Keywords: Biology ; Anatomy & Physiology
    ISSN: 0896-6273
    E-ISSN: 1097-4199
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  • 10
    In: Molecular Microbiology, June 2010, Vol.76(5), pp.1250-1265
    Description: The conjugative IncHI1 plasmid pSfR27 from 2a strain 2457T encodes the Sfh protein, a paralogue of the global transcriptional repressor H‐NS. Sfh allows pSfR27 to be transmitted to new bacterial hosts with minimal impact on host fitness, providing a ‘stealth’ function whose molecular mechanism has yet to be determined. The impact of the Sfh protein on the serovar Typhimurium transcriptome was assessed and binding sites for Sfh in the Typhimurium genome were identified by chromatin immunoprecipitation. Sfh did not bind uniquely to any sites. Instead, it bound to a subset of the larger H‐NS regulatory network. Analysis of Sfh binding in the absence of H‐NS revealed a greatly expanded population of Sfh binding sites that included the majority of H‐NS target genes. Furthermore, the presence of plasmid pSfR27 caused a decrease in H‐NS interactions with the Typhimurium chromosome, suggesting that the A + T‐rich DNA of this large plasmid acts to titrate H‐NS, removing it from chromosomal locations. It is proposed that Sfh acts as a molecular backup for H‐NS and that it provides its ‘stealth’ function by replacing H‐NS on the chromosome, thus minimizing disturbances to the H‐NS‐DNA binding pattern in cells that acquire pSfR27.
    Keywords: Fighter Planes -- Analysis ; Chromatin -- Analysis ; Preventive Medicine -- Analysis ; Salmonella Typhimurium -- Analysis ; Genomics -- Analysis;
    ISSN: 0950-382X
    E-ISSN: 1365-2958
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