The Bangor Gambling Task: Characterising the performance of survivors of traumatic brain injury

The Bangor Gambling Task (BGT, Bowman & Turnbull, 2004) is a simple test of emotion-based decision-making, with contingencies varying across five blocks of 20 trials. This is the first study to characterise BGT performance in survivors of traumatic brain injury (TBI) relative to healthy controls. The study also aimed to explore sub-groups (cluster analysis), and identify predictors of task performance (multiple regression). Thirty survivors of TBI and 39 controls completed the BGT and measures of premorbid IQ, working memory, and executive function. Results showed that survivors of TBI made more gamble choices than controls (total BGT score), although the groups did not significantly differ when using a cut-off score for ‘impaired’ performance. Unexpectedly, the groups did not significantly differ in their performance across the blocks, however, the cluster analysis revealed three subgroups (with survivors of TBI and controls represented in each cluster). Findings also indicated that age and group were significant predictors of overall BGT performance, but not gender, premorbid IQ, or working memory and executive function. In conclusion, the study findings are consistent with an individual differences account of emotion-based decision-making, and a number of issues need to be addressed prior to recommending the clinical use of the BGT

Structural characterization of Clostridium sordellii spores of diverse human, animal, and environmental origin and comparison to Clostridium difficile spores

© 2017 Rabi et al. Clostridium sordellii is an often-lethal bacterium causing human and animal disease. Crucial to the infectious cycle of C. sordellii is its ability to produce spores, which can germinate into toxin-producing vegetative bacteria under favorable conditions. However, structural details of the C. sordellii spore are lacking. Here, we used a range of electron microscopy techniques together with superresolution optical microscopy to characterize the C. sordellii spore morphology with an emphasis on the exosporium. The C. sordellii spore is made up of multiple layers with the exosporium presenting as a smooth balloon-like structure that is open at the spore poles. Focusing on the outer spore layers, we compared the morphologies of C. sordellii spores derived from different strains and determined that there is some variation between the spores, most notably with spores of some strains having tubular appendages. Since Clostridium difficile is a close relative of C. sordellii, their spores were compared by electron microscopy and their exosporia were found to be distinctly different from each other. This study therefore provides new structural details of the C. sordellii spore and offers insights into the physical structure of the exosporium across clostridial species

Bacterial Stigmergy: An Organising Principle of Multicellular Collective Behaviours of Bacteria

The self-organisation of collective behaviours often manifests as dramatic patterns of emergent large-scale order. This is true for relatively "simple" entities such as microbial communities and robot "swarms, " through to more complex self-organised systems such as those displayed by social insects, migrating herds, and many human activities. The principle of stigmergy describes those self-organised phenomena that emerge as a consequence of indirect communication between individuals of the group through the generation of persistent cues in the environment. Interestingly, despite numerous examples of multicellular behaviours of bacteria, the principle of stigmergy has yet to become an accepted theoretical framework that describes how bacterial collectives self-organise. Here we review some examples of multicellular bacterial behaviours in the context of stigmergy with the aim of bringing this powerful and elegant self-organisation principle to the attention of the microbial research community

A36-dependent Actin Filament Nucleation Promotes Release of Vaccinia Virus

Cell-to-cell transmission of vaccinia virus can be mediated by enveloped virions that remain attached to the outer surface of the cell or those released into the medium. During egress, the outer membrane of the double-enveloped virus fuses with the plasma membrane leaving extracellular virus attached to the cell surface via viral envelope proteins. Here we report that F-actin nucleation by the viral protein A36 promotes the disengagement of virus attachment and release of enveloped virus. Cells infected with the A36(YdF) virus, which has mutations at two critical tyrosine residues abrogating localised actin nucleation, displayed a 10-fold reduction in virus release. We examined A36(YdF) infected cells by transmission electron microscopy and observed that during release, virus appeared trapped in small invaginations at the plasma membrane. To further characterise the mechanism by which actin nucleation drives the dissociation of enveloped virus from the cell surface, we examined recombinant viruses by super-resolution microscopy. Fluorescently-tagged A36 was visualised at sub-viral resolution to image cell-virus attachment in mutant and parental backgrounds. We confirmed that A36(YdF) extracellular virus remained closely associated to the plasma membrane in small membrane pits. Virus-induced actin nucleation reduced the extent of association, thereby promoting the untethering of virus from the cell surface. Virus release can be enhanced via a point mutation in the luminal region of B5 (P189S), another virus envelope protein. We found that the B5(P189S) mutation led to reduced contact between extracellular virus and the host membrane during release, even in the absence of virus-induced actin nucleation. Our results posit that during release virus is tightly tethered to the host cell through interactions mediated by viral envelope proteins. Untethering of virus into the surrounding extracellular space requires these interactions be relieved, either through the force of actin nucleation or by mutations in luminal proteins that weaken these interactions.This work was outlined and supported by Project Grant #632785 of the National Health and Medical Research Council of Australia and The Australian Research Council Federation Discovery Project #1096623. CBW was supported by a National Health and Medical Research Council of Australia Senior Research Fellowship #571905. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Pseudomonas aeruginosa is capable of natural transformation in biofilms

Natural transformation is a mechanism that enables competent bacteria to acquire naked, exogenous DNA from the environment. It is a key process that facilitates the dissemination of antibiotic resistance and virulence determinants throughout bacterial populations. Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that produces large quantities of extracellular DNA (eDNA) that is required for biofilm formation. P. aeruginosa has a remarkable level of genome plasticity and diversity that suggests a high degree of horizontal gene transfer and recombination but is thought to be incapable of natural transformation. Here we show that P. aeruginosa possesses homologues of all proteins known to be involved in natural transformation in other bacterial species. We found that P. aeruginosa in biofilms is competent for natural transformation of both genomic and plasmid DNA. Furthermore, we demonstrate that type-IV pili (T4P) facilitate but are not absolutely essential for natural transformation in P. aeruginosa

Stepwise dissection of Plasmodium falciparum merozoite invasion of the human erythrocyte

A critical step in establishing malaria parasite infection is the ability of the blood stage merozoite to invade erythrocytes. However, much of our understanding about the cell biology of this process has remained unchanged since seminal work, more than 30 years ago, defined the steps of entry by light and electron microscopy. These studies were, however, only possible using merozoites from simian and avian malaria parasite species, given the poor viability of merozoites from human parasites, specifically Plasmodium falciparum. In contrast, critical invasion proteins have been best described for human or mouse parasite species. Thus our understanding about the molecular and cellular coordination of the entire process of invasion is still largely unknown. Towards addressing this gap, we recently developed a method for harvesting viable P. falciparum merozoites, permitting detailed investigation of the molecular events of merozoite invasio

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes to Adopt a Tumorigenic Phenotype.

BACKGROUND: Throughout Asia, there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes, including chronic inflammation and secretion of parasite proteins into the biliary epithelium, drive infection toward cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown. METHODS: Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterized the EV proteome and associated changes in cholangiocytes after EV uptake, and we detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and interleukin 6 (IL-6) secretion was measured to assess the impact of EV internalization. RESULTS: EVs were identified in fluke culture medium and bile specimens from infected hosts. EVs internalized by cholangiocytes drove cell proliferation and IL-6 secretion and induced changes in protein expression associated with endocytosis, wound repair, and cancer. Antibodies to an O. viverrini tetraspanin blocked EV uptake and IL-6 secretion by cholangiocytes. CONCLUSIONS: This is the first time that EVs from a multicellular pathogen have been identified in host tissues. Our findings imply a role for O. viverrini EVs in pathogenesis and highlight an approach to vaccine development for this infectious cancer.This work was supported by a Project Grant (APP1085309) from the National Health and Medical Research Council of Australia (NHMRC). AL is supported by a NHMRC principal research fellowship. SC was supported by the Thailand Research Fund (TRF)-the Royal Golden Jubilee PhD scholarship (RGJ) through Dr. Banchob Sripa.This is the final version. It was first published by OUP at http://dx.doi.org/10.1093/infdis/jiv29

Multiple holins contribute to extracellular DNA release in Pseudomonas aeruginosa biofilms

Bacterial biofilms are composed of aggregates of cells encased within a matrix of extracellular polymeric substances (EPS). One key EPS component is extracellular DNA (eDNA), which acts as a ‘glue’, facilitating cell–cell and cell–substratum interactions. We have previously demonstrated that eDNA is produced in Pseudomonas aeruginosa biofilms via explosive cell lysis. This phenomenon involves a subset of the bacterial population explosively lysing, due to peptidoglycan degradation by the endolysin Lys. Here we demonstrate that in P. aeruginosa three holins, AlpB, CidA and Hol, are involved in Lys-mediated eDNA release within both submerged (hydrated) and interstitial (actively expanding) biofilms, albeit to different extents, depending upon the type of biofilm and the stage of biofilm development. We also demonstrate that eDNA release events determine the sites at which cells begin to cluster to initiate microcolony formation during the early stages of submerged biofilm development. Furthermore, our results show that sustained release of eDNA is required for cell cluster consolidation and subsequent microcolony development in submerged biofilms. Overall, this study adds to our understanding of how eDNA release is controlled temporally and spatially within P. aeruginosa biofilms