Characterisation of the effects of salicylidene acylhydrazide compounds on type three secretion in Escherichia coli O157:H7

Recent work has highlighted a number of compounds that target bacterial virulence by affecting gene regulation. In this work, we show that small-molecule inhibitors affect the expression of the type III secretion system (T3SS) of <i>Escherichia coli</i> O157:H7 in liquid culture and when the bacteria are attached to bovine epithelial cells. The inhibition of T3SS expression resulted in a reduction in the capacity of the bacteria to form attaching and effacing lesions. Our results show a marked variation in the ability of four structurally-related compounds to inhibit the T3SS of a panel of isolates. Using transcriptomics, we provide a comprehensive analysis of the conserved- and inhibitor-specific transcriptional responses to the four compounds. These analyses of gene expression show that numerous virulence genes, located on horizontally-acquired DNA elements, are affected by the compounds but the number of genes significantly affected varied markedly between the compounds. Overall, we highlight the importance of assessing the effect of such "anti-virulence" agents on a range of isolates and discuss the possible mechanisms which may lead to the co-ordinate down-regulation of horizontally acquired virulence genes

The domain-specificity of face matching impairments in 40 cases of developmental prosopagnosia.

A prevailing debate in the psychological literature concerns the domain-specificity of the face recognition system, where evidence from typical and neurological participants has been interpreted as evidence that faces are "special". Although several studies have investigated the same question in cases of developmental prosopagnosia, the vast majority of this evidence has recently been discounted due to methodological concerns. This leaves an uncomfortable void in the literature, restricting our understanding of the typical and atypical development of the face recognition system. The current study addressed this issue in 40 individuals with developmental prosopagnosia, completing a sequential same/different face and biological (hands) and non-biological (houses) object matching task, with upright and inverted conditions. Findings support domain-specific accounts of face-processing for both hands and houses: while significant correlations emerged between all the object categories, no condition correlated with performance in the upright faces condition. Further, a categorical analysis demonstrated that, when face matching was impaired, object matching skills were classically dissociated in six out of 15 individuals (four for both categories). These findings provide evidence about domain-specificity in developmental disorders of face recognition, and present a theoretically-driven means of partitioning developmental prosopagnosia

Mating ecology explains patterns of genome elimination

This research has been supported by a Royal Society University Research Fellowship (AG), a Royal Society Newton International Fellowship (LR) and two NERC Independent Research Fellowships (AG & LR).Genome elimination – whereby an individual discards chromosomes inherited from one parent, and transmits only those inherited from the other parent – is found across thousands of animal species. It is more common in association with inbreeding, under male heterogamety, in males, and in the form of paternal genome elimination. However, the reasons for this broad pattern remain unclear. We develop a mathematical model to determine how degree of inbreeding, sex determination, genomic location, pattern of gene expression and parental origin of the eliminated genome interact to determine the fate of genome-elimination alleles. We find that: inbreeding promotes paternal genome elimination in the heterogametic sex; this may incur population extinction under female heterogamety, owing to eradication of males; and extinction is averted under male heterogamety, owing to countervailing sex-ratio selection. Thus, we explain the observed pattern of genome elimination. Our results highlight the interaction between mating system, sex-ratio selection and intragenomic conflict.Publisher PDFPeer reviewe

A Reexamination of Source Monitoring Deficits in the Elderly: Evidence for Independent Age Deficits of Item and Source Memory

Within the experimental literature there is substantial evidence of larger age-related deficits in retrieving source information relative to item-based information. However, this evidence is potentially subject to methodological criticism given that several studies have argued for the presence of source-monitoring deficits by examining source memory contingent on correct recall of item information but not the reverse. In order to address this potential shortcoming our study examines recall of both item information contingent on correct source judgement and source-based information contingent on correct recall of item information. We demonstrate that when this novel type of analysis is conducted, there are age deficits for both source and item information, and no evidence of a selectively greater source-monitoring deficit in the elderly. The results are discussed with reference to two overarching theoretical positions concerning age-related deficits in memory performance

Controlling injection: regulation of type III secretion in enterohaemorrhagic <i>Escherichia coli</i>

Type III secretion (T3S) systems enable the injection of bacterial proteins through membrane barriers into host cells, either from outside the host cell or from within a vacuole. This system is required for colonization of their ruminant reservoir hosts by enterohaemorrhagic &lt;i&gt;Escherichia coli&lt;/i&gt; (EHEC) and might also be important for the etiology of disease in the incidental human host. T3S systems of &lt;i&gt;E. coli&lt;/i&gt; inject a cocktail of proteins into epithelial cells that enables bacterial attachment and promotes longer-term colonization in the animal. Here, we review recent progress in our understanding of the regulation of T3S in EHEC, focusing on the induction and assembly of the T3S system, the co-ordination of effector protein expression, and the timing of effector protein export through the apparatus. Strain variation is often associated with differences in bacteriophages encoding the production of Shiga toxin and in multiple cryptic prophage elements that can encode effector proteins and T3S regulators. It is evident that this repertoire of phage-related sequences results in the different levels of T3S demonstrated between strains, with implications for EHEC epidemiology and strain evolution

Hydrodynamics of DNA confined in nanoslits and nanochannels

Modeling the dynamics of a confined, semi exible polymer is a challenging problem, owing to the complicated interplay between the configurations of the chain, which are strongly affected by the length scale for the confinement relative to the persistence length of the chain, and the polymer-wall hydrodynamic interactions. At the same time, understanding these dynamics are crucial to the advancement of emerging genomic technologies that use confinement to stretch out DNA and “read” a genomic signature. In this mini-review, we begin by considering what is known experimentally and theoretically about the friction of a wormlike chain such as DNA confined in a slit or a channel. We then discuss how to estimate the friction coefficient of such a chain, either with dynamic simulations or via Monte Carlo sampling and the Kirk-wood pre-averaging approximation. We then review our recent work on computing the diffusivity of DNA in nanoslits and nanochannels, and conclude with some promising avenues for future work and caveats about our approach