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Search Results: 1 - 10 of 12305 matches for " Stephen Bentley "
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New Knowledge from Old: In silico discovery of novel protein domains in Streptomyces coelicolor
Corin Yeats, Stephen Bentley, Alex Bateman
BMC Microbiology , 2003, DOI: 10.1186/1471-2180-3-3
Abstract: Two automated methods were employed to rapidly generate an optimised set of targets, which were subsequently analysed manually. A final set of 37 domains or structural repeats, represented 204 times in the genome, was developed. Using these families enabled us to correlate items of information from many different resources. Several immediately enhance our understanding both of S. coelicolor and also general bacterial molecular mechanisms, including cell wall biosynthesis regulation and streptomycete telomere maintenance.Delineation of protein domain families enables detailed analysis of protein function, as well as identification of likely regions or residues of particular interest. Hence this kind of prior approach can increase the rate of discovery in the laboratory. Furthermore we demonstrate that using this type of in silico method it is possible to fairly rapidly generate new biological information from previously uncorrelated data.Streptomyces coelicolor is a representative of a group of high G+C Gram positive bacteria whose successful adaptation to their niche is demonstrated by their almost ubiquitous presence in soil. This is largely accounted for by their broad metabolic capacity allowing them to cope with the many variables in their environment. They are able to utilise a wide range of food sources including the debris from plants, insects and fungi. Streptomycetes are also famed for their production of a range of secondary metabolites including antibiotics and other chemotherapeutic compounds.Unusually for bacteria, streptomycetes exhibit complex multicellular development, with branching, filamentous mycelia giving rise to aerial hyphae which in turn bear long chains of reproductive spores. These three developmental stages also display differential 'tissue-specific' gene expression.Also unusual is the size and structure of streptomycete chromosomes. Streptomyces coelicolor has a linear chromosome which at 8,667,507 base pairs is the largest complete bact
Bioinformatic identification of novel regulatory DNA sequence motifs in Streptomyces coelicolor
David J Studholme, Stephen D Bentley, Jan Kormanec
BMC Microbiology , 2004, DOI: 10.1186/1471-2180-4-14
Abstract: The method involved production of position-specific weight matrices from alignments of over-represented words of DNA sequence. We generated 2497 weight matrices, each representing a candidate regulatory DNA sequence motif. We scanned the genome sequence of S. coelicolor against each of these matrices. A DNA sequence motif represented by one of the matrices was found preferentially in non-coding sequences immediately upstream of genes involved in polysaccharide degradation, including several that encode chitinases. This motif (TGGTCTAGACCA) was also found upstream of genes encoding components of the phosphoenolpyruvate phosphotransfer system (PTS). We hypothesise that this DNA sequence motif represents a regulatory element that is responsive to availability of carbon-sources.Other motifs of potential biological significance were found upstream of genes implicated in secondary metabolism (TTAGGTtAGgCTaACCTAA), sigma factors (TGACN19TGAC), DNA replication and repair (ttgtCAGTGN13TGGA), nucleotide conversions (CTACgcNCGTAG), and ArsR (TCAGN12TCAG). A motif found upstream of genes involved in chromosome replication (TGTCagtgcN7Tagg) was similar to a previously described motif found in UV-responsive promoters.We successfully applied a recently published in silico method to identify conserved sequence motifs in S. coelicolor that may be biologically significant as regulatory elements. Our data are broadly consistent with and further extend data from previously published studies. We invite experimental testing of our hypotheses in vitro and in vivo.The complete functional information encoded in a genome consists not only of the genes, encoding proteins and RNAs, but also structural and regulatory elements. Complete genome sequences are generated much faster than regulatory sites can be determined by experiment, and so there is a need for computational prediction and detection of regulatory elements in complete genomes.In some cases, a set of co-regulated genes (i.e. a regul
Mobile genetic element proliferation and gene inactivation impact over the genome structure and metabolic capabilities of Sodalis glossinidius, the secondary endosymbiont of tsetse flies
Eugeni Belda, Andrés Moya, Stephen Bentley, Francisco J Silva
BMC Genomics , 2010, DOI: 10.1186/1471-2164-11-449
Abstract: A detailed characterization of mobile genetic elements and pseudogenes reveals a massive presence of different types of prophage elements together with five different families of IS elements that have proliferated across the genome of Sodalis glossinidius at different levels. In addition, a detailed survey of intergenic regions allowed the characterization of 1501 pseudogenes, a much higher number than the 972 pseudogenes described in the original annotation. Pseudogene structure reveals a minor impact of mobile genetic element proliferation in the process of gene inactivation, with most of pseudogenes originated by multiple frameshift mutations and premature stop codons. The comparison of metabolic profiles of Sodalis glossinidius and tsetse fly primary endosymbiont Wiglesworthia glossinidia based on their whole gene and pseudogene repertoires revealed a novel case of pathway inactivation, the arginine biosynthesis, in Sodalis glossinidius together with a possible case of metabolic complementation with Wigglesworthia glossinidia for thiamine biosynthesis.The complete re-analysis of the genome sequence of Sodalis glossinidius reveals novel insights in the evolutionary transition from a free-living ancestor to a host-dependent lifestyle, with a massive proliferation of mobile genetic elements mainly of phage origin although with minor impact in the process of gene inactivation that is taking place in this bacterial genome. The metabolic analysis of the whole endosymbiotic consortia of tsetse flies have revealed a possible phenomenon of metabolic complementation between primary and secondary endosymbionts that can contribute to explain the co-existence of both bacterial endosymbionts in the context of the tsetse host.Symbiotic associations between bacteria and insects are widespread in nature, being postulated as one of the key factors of their evolutionary success. Bacterial endosymbionts allow insects to colonize novel ecological niches characterized by unbalanced n
Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes.
Bentley Stephen D,Aanensen David M,Mavroidi Angeliki,Saunders David
PLOS Genetics , 2006,
Abstract: Several major invasive bacterial pathogens are encapsulated. Expression of a polysaccharide capsule is essential for survival in the blood, and thus for virulence, but also is a target for host antibodies and the basis for effective vaccines. Encapsulated species typically exhibit antigenic variation and express one of a number of immunochemically distinct capsular polysaccharides that define serotypes. We provide the sequences of the capsular biosynthetic genes of all 90 serotypes of Streptococcus pneumoniae and relate these to the known polysaccharide structures and patterns of immunological reactivity of typing sera, thereby providing the most complete understanding of the genetics and origins of bacterial polysaccharide diversity, laying the foundations for molecular serotyping. This is the first time, to our knowledge, that a complete repertoire of capsular biosynthetic genes has been available, enabling a holistic analysis of a bacterial polysaccharide biosynthesis system. Remarkably, the total size of alternative coding DNA at this one locus exceeds 1.8 Mbp, almost equivalent to the entire S. pneumoniae chromosomal complement.
Investigations into genome diversity of Haemophilus influenzae using whole genome sequencing of clinical isolates and laboratory transformants
Power Peter M,Bentley Stephen D,Parkhill Julian,Moxon E
BMC Microbiology , 2012, DOI: 10.1186/1471-2180-12-273
Abstract: Background Haemophilus influenzae is an important human commensal pathogen associated with significant levels of disease. High-throughput DNA sequencing was used to investigate differences in genome content within this species. Results Genomic DNA sequence was obtained from 85 strains of H. influenzae and from other related species, selected based on geographical site of isolation, disease association and documented genotypic and phenotypic differences. When compared by Mauve alignment these indicated groupings of H. influenzae that were consistent with previously published analyses; capsule expressing strains fell into two distinct groups and those of serotype b (Hib) were found in two closely positioned lineages. For 18 Hib strains representing both lineages we found many discrete regions (up to 40% of the total genome) displaying sequence variation when compared to a common reference strain. Evidence that this naturally occurring pattern of inter-strain variation in H. influenzae can be mediated by transformation was obtained through sequencing DNA obtained from a pool of 200 independent transformants of a recipient (strain Rd) using donor DNA from a heterologous Hib strain (Eagan). Conclusion Much of the inter-strain variation in genome sequence in H. influenzae is likely the result of inter-strain exchanges of DNA, most plausibly through transformation.
A High-Resolution View of Genome-Wide Pneumococcal Transformation
Nicholas J. Croucher ,Simon R. Harris,Lars Barquist,Julian Parkhill,Stephen D. Bentley
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002745
Abstract: Transformation is an important mechanism of microbial evolution through which bacteria have been observed to rapidly adapt in response to clinical interventions; examples include facilitating vaccine evasion and the development of penicillin resistance in the major respiratory pathogen Streptococcus pneumoniae. To characterise the process in detail, the genomes of 124 S. pneumoniae isolates produced through in vitro transformation were sequenced and recombination events detected. Those recombinations importing the selected marker were independent of unselected events elsewhere in the genome, the positions of which were not significantly affected by local sequence similarity between donor and recipient or mismatch repair processes. However, both types of recombinations were sometimes mosaic, with multiple non-contiguous segments originating from the same molecule of donor DNA. The lengths of the unselected events were exponentially distributed with a mean of 2.3 kb, implying that recombinations are stochastically resolved with a fixed per base probability of 4.4×10?4 bp?1. This distribution of recombination sizes, coupled with an observed under representation of large insertions within transferred sequence, suggests transformation has the potential to reduce the size of bacterial genomes, and is unlikely to act as an efficient mechanism for the uptake of accessory genomic loci.
Identification, variation and transcription of pneumococcal repeat sequences
Nicholas J Croucher, Georgios S Vernikos, Julian Parkhill, Stephen D Bentley
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-120
Abstract: Analysis of the genome of S. pneumoniae ATCC 700669 revealed the presence of a third repeat family, which we have named SPRITE. All three repeats are present at a reduced density in the genome of the closely related species S. mitis. However, they are almost entirely absent from all other streptococci, although a set of elements related to the pneumococcal BOX repeat was identified in the zoonotic pathogen S. suis. In conjunction with information regarding their distribution within the pneumococcal chromosome, this suggests that it is unlikely that these repeats are specialised sequences performing a particular role for the host, but rather that they constitute parasitic elements. However, comparing insertion sites between pneumococcal sequences indicates that they appear to transpose at a much lower rate than IS elements. Some large BOX elements in S. pneumoniae were found to encode open reading frames on both strands of the genome, whilst another was found to form a composite RNA structure with two T box riboswitches. In multiple cases, such BOX elements were demonstrated as being expressed using directional RNA-seq and RT-PCR.BOX, RUP and SPRITE repeats appear to have proliferated extensively throughout the pneumococcal chromosome during the species' past, but novel insertions are currently occurring at a relatively slow rate. Through their extensive secondary structures, they seem likely to affect the expression of genes with which they are co-transcribed. Software for annotation of these repeats is freely available from ftp://ftp.sanger.ac.uk/pub/pathogens/strep_repeats/ webcite.Small interspersed repeats, spatially separated genomic regions of similar sequence typically < 200 bp in length, are frequently found in bacterial chromosomes [1]. These can be classified as either 'simple', when consisting of a single repeated unit, or 'composite', when comprised of a combination of different subsequences arranged in particular patterns [2]. For example, a number of e
Re-annotation and re-analysis of the Campylobacter jejuni NCTC11168 genome sequence
Ozan Gundogdu, Stephen D Bentley, Matt T Holden, Julian Parkhill, Nick Dorrell, Brendan W Wren
BMC Genomics , 2007, DOI: 10.1186/1471-2164-8-162
Abstract: Re-annotation was carried out using sequence database searches such as FASTA, along with programs such as TMHMM for additional support. The re-annotation also utilises sequence data from additional Campylobacter strains and species not available during the original annotation. Re-annotation was accompanied by a full literature search that was incorporated into the updated EMBL file [EMBL: AL111168]. The C. jejuni NCTC11168 re-annotation reduced the total number of coding sequences from 1654 to 1643, of which 90.0% have additional information regarding the identification of new motifs and/or relevant literature. Re-annotation has led to 18.2% of coding sequence product functions being revised.Major updates were made to genes involved in the biosynthesis of important surface structures such as lipooligosaccharide, capsule and both O- and N-linked glycosylation. This re-annotation will be a key resource for Campylobacter research and will also provide a prototype for the re-annotation and re-interpretation of other bacterial genomes.Campylobacter jejuni is the leading bacterial cause of human gastroenteritis in the developed world [1]. C. jejuni infection has also been associated with post-infection sequelae including septicaemia and neuropathies such as Guillain-Barré Syndrome (GBS) [2]. Infection has largely been linked with the consumption of contaminated poultry or meat products. Given the socioeconomic importance of this pathogen, it is surprising that the ecology, the epidemiology and, in particular, the pathogenesis are still so poorly understood [3]. The lack of information on this problematic pathogen was one of the main driving forces for the original C. jejuni NCTC11168 genome project published in 2000 [4], and equally is why a re-annotation and re-analysis of the genome is required.Since the publication of the C. jejuni NCTC11168 genome sequence in 2000, there has been a spectacular increase in research on this important human pathogen. One result of this h
When Utility Jumps: The Value of Having Cash in the Hand  [PDF]
Kurt W. Rotthoff, Bentley Coffey
Theoretical Economics Letters (TEL) , 2018, DOI: 10.4236/tel.2018.81004
Abstract: Different theoretical explanations have been developed for seemingly inconsistent actions that deal with varying levels of risk and time. We propose a simple model of utility that unifies these seemingly separate phenomena, while not departing too far from the standard models of utility maximization already in use. Our driving assumption is that preferences over riskier outcomes discontinuously depart from preferences under certainty; a jump from no risk to some risk is fundamentally different from a movement of some risk to more risk.
Europeanization of the World or Globalization of Europe?
Jerry Bentley
Religions , 2012, DOI: 10.3390/rel3020441
Abstract: Building on his long career as a distinguished historian of early modern Europe, John Miles Headley has recently turned his gaze to the influence of Europe in the larger world. In The Europeanization of the World, Headley makes an insistent case for the uniqueness of European values—particularly human rights and democracy—and argues that these values are Europe’s most precious gifts to the larger world. Without seeking to diminish the remarkable intellectual and cultural achievements of European peoples, this presentation will suggest a more nuanced view of relations between Europe and the larger world. Human rights and democracy mean different things to different peoples in different contexts at different times, and there have in fact been numerous expressions of both in societies beyond Europe. Furthermore, European theorists of human rights and democracy drew influence from societies beyond Europe. To the extent that the Europeanization of the world is a persuasive idea, it is possible only because of a prior globalization of Europe.
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