1,721,048 research outputs found
Synergistic activity of mobile genetic element defences in Streptococcus pneumoniae
Full text linkA diverse set of mobile genetic elements (MGEs) transmit between Streptococcus pneumoniae
cells, but many isolates remain uninfected. The best-characterised defences against horizontal
transmission of MGEs are restriction-modification systems (RMSs), of which there are two
phase-variable examples in S. pneumoniae. Additionally, the transformation machinery has been
proposed to limit vertical transmission of chromosomally integrated MGEs. This work describes how
these mechanisms can act in concert. Experimental data demonstrate RMS phase variation occurs
at a sub-maximal rate. Simulations suggest this may be optimal if MGEs are sometimes vertically
inherited, as it reduces the probability that an infected cell will switch between RMS variants while
the MGE is invading the population, and thereby undermine the restriction barrier. Such vertically
inherited MGEs can be deleted by transformation. The lack of between-strain transformation hotspots
at known prophage att sites suggests transformation cannot remove an MGE from a strain in which it
is fixed. However, simulations confirmed that transformation was nevertheless eective at preventing
the spread of MGEs into a previously uninfected cell population, if a recombination barrier existed
between co-colonising strains. Further simulations combining these eects of phase variable RMSs
and transformation found they synergistically inhibited MGEs spreading, through limiting both
vertical and horizontal transmission
Diverse regulatory pathways modulate bet hedging of competence induction in epigenetically-differentiated phase variants of Streptococcus pneumoniae
Full text linkDespite enabling Streptococcus pneumoniae to acquire antibiotic resistance and evade vaccine-induced immunity, transformation occurs at variable rates across pneumococci. Phase variants of isolate RMV7, distinguished by altered methylation patterns driven by the translocating variable restriction-modification (tvr) locus, differed significantly in their transformation efficiencies and biofilm thicknesses. These differences were replicated when the corresponding tvr alleles were introduced into an RMV7 derivative lacking the locus. RNA-seq identified differential expression of the type 1 pilus, causing the variation in biofilm formation, and inhibition of competence induction in the less transformable variant, RMV7domi. This was partly attributable to RMV7domi's lower expression of ManLMN, which promoted competence induction through importing N-acetylglucosamine. This effect was potentiated by analogues of some proteobacterial competence regulatory machinery. Additionally, one of RMV7domi's phage-related chromosomal island was relatively active, which inhibited transformation by increasing expression of the stress response proteins ClpP and HrcA. However, HrcA increased competence induction in the other variant, with its effects depending on Ca2+ supplementation and heat shock. Hence the heterogeneity in transformation efficiency likely reflects the diverse signalling pathways by which it is affected. This regulatory complexity will modulate population-wide responses to synchronising quorum sensing signals to produce co-ordinated yet stochastic bet hedging behaviour.Graphical Abstrac
Excision-reintegration at a pneumococcal phase-variable restriction-modification locus drives within- and between-strain epigenetic differentiation and inhibits gene acquisition
Full text linkPhase-variation of Type I restriction-modification
systems can rapidly alter the sequence motifs they
target, diversifying both the epigenetic patterns
and endonuclease activity within clonally descended
populations. Here, we characterize the Streptococcus
pneumoniae SpnIV phase-variable Type I RMS,
encoded by the translocating variable restriction
(tvr) locus, to identify its target motifs, mechanism
and regulation of phase variation, and effects
on exchange of sequence through transformation.
The specificity-determining hsdS genes were
shuffled through a recombinase-mediated excisionreintegration
mechanism involving circular intermediatemolecules,
guided by two types of direct repeat.
The rate of rearrangements was limited by an attenuator
and toxin-antitoxin system homologs that inhibited
recombinase gene transcription. Target motifs
for both the SpnIV, and multiple Type II, MTases were
identified through methylation-sensitive sequencing
of a panel of recombinase-null mutants. This demonstrated
the species-wide diversity observed at the
tvr locus can likely specify nine different methylation
patterns. This will reduce sequence exchange in
this diverse species, as the native form of the SpnIV
RMS was demonstrated to inhibit the acquisition of
genomic islands by transformation. Hence the tvr locus
can drive variation in genome methylation both
within and between strains, and limits the genomic
plasticity of S. pneumoniae
Phase-variable methylation and epigenetic regulation by type I restriction-modification systems
No full textEpigenetic modifications in bacteria, such as DNA methylation, have been shown to affect gene regulation, thereby
generating cells that are isogenic but with distinctly different phenotypes. Restriction–modification (RM) systems contain
prototypic methylases that are responsible for much of bacterial DNA methylation. This review focuses on a distinctive
group of type I RM loci that , through phase variation, can modify their methylation target specificity and can thereby
switch bacteria between alternative patterns of DNA methylation. Phase variation occurs at the level of the target
recognition domains of the hsdS (specificity) gene via reversible recombination processes acting upon multiple hsdS alleles.
We describe the global distribution of such loci throughout the prokaryotic kingdom and highlight the differences in loci
structure across the various bacterial species. Although RM systems are often considered simply as an evolutionary
response to bacteriophages, these multi-hsdS type I systems have also shown the capacity to change bacterial phenotypes.
The ability of these RM systems to allow bacteria to reversibly switch between different physiological states, combined with
the existence of such loci across many species of medical and industrial importance, highlights the potential of
phase-variable DNA methylation to act as a global regulatory mechanism in bacteria
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis
Full text linkRecent studies have provided evidence for rapid pathogen genome diversification, some of which could potentially affect the
course of disease. We have previously described such variation seen between isolates infecting the blood and cerebrospinal
fluid (CSF) of a single patient during a case of bacterial meningitis. Here, we performed whole-genome sequencing of paired
isolates from the blood and CSF of 869 meningitis patients to determine whether such variation frequently occurs between
these two niches in cases of bacterial meningitis. Using a combination of reference-free variant calling approaches, we show
that no genetic adaptation occurs in either invaded niche during bacterial meningitis for two major pathogen species,
Streptococcus pneumoniae and Neisseria meningitidis. This study therefore shows that the bacteria capable of causing
meningitis are already able to do this upon entering the blood, and no further sequence change is necessary to cross the
blood–brain barrier. Our findings place the focus back on bacterial evolution between nasopharyngeal carriage and invasion,
or diversity of the host, as likely mechanisms for determining invasiveness
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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