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

Two new Australian fungus-feeding thrips in two new Plectrothripini genera (Thysanoptera, Phlaeothripinae)

Two new genera are erected of plectrothripine Phlaeothripidae from northern Australia, each based on a single species. One has a long stout projection ventrally on the second antennal segment, the other has a unique arrangement of the dorsal facets of the compound eyes. In both of them the thoracic ventral sclerites are extensively eroded. The tribe Plectrothripini is one of the few apparently discrete lineages within the large and complex subfamily Phlaeothripinae (Dang et al. 2014). The species in this Tribe are all fungus-feeders on dead branches, and the group is found in the tropics worldwide. Okajima (1981) provided an extensive, illustrated account of the Plectrothripini, recognising 10 genera and almost 50 species, to which Tyagi et al. (2016) added one further species. Six of these genera remain monotypic, with two genera each comprising five or six species, and Plectrothrips itself with about 30 species. This asymmetry of taxon distribution, with a high proportion of monotypic genera, is due to the presence of certain characters in unusual autapomorphic states. Phylogenetic relationships within the tribe are further confused here through the diagnosis of two new monotypic genera for species from the tropical north of Australia. One of these new species has a bizarre projection ventrally on the second antennal segment (Fig. 5), whilst the other has the structure of the compound eyes unique amongst Phlaeothripidae (Figs 7, 8). Membership of the Tribe Plectrothripini is fairly clear, with the species sharing most of the following character states as indicated by Okajima (1981): antennae 8-segmented, segment II with the campaniform sensillum on the basal half, III–IV with a variable number of short, stout sense cones, VIII elongate with narrow base. Head with posterior ocelli close to compound eyes. Pronotum commonly with sclerotised plate eroded and reduced; prosternal basantra absent; fore tarsal tooth large; apex of hind tibiae commonly with stout setae. Pelta wide at base, tergite II eroded laterally; sternites often with reticulate glandular areas

Genera of fungivorous Phlaeothripinae (Thysanoptera) from dead branches and leaf-litter in Australia

An illustrated key is provided for the identification of 39 genera of Thysanoptera-Phlaeothripinae with species that live in association with dead branches and leaf-litter in Australia and are considered to be fungus-feeding. Seven of these gen-era are not previously recorded from this continent, including un-named species of Deplorothrips, Malacothrips, Mystro-thrips, Preeriella and Tylothrips, together with Azaleothrips lepidus Okajima and Terthrothrips ananthakrishnani Kudo. A brief generic diagnosis is provided for each genus, together with comments on systematic problems and numbers of species. Copyright © 2013 Magnolia Press

The Man Who Mistook His Neuropsychologist For a Popstar: When Configural Processing Fails in Acquired Prosopagnosia

We report the case of an individual with acquired prosopagnosia who experiences extreme difficulties in recognizing familiar faces in everyday life despite excellent object recognition skills. Formal testing indicates that he is also severely impaired at remembering pre-experimentally unfamiliar faces and that he takes an extremely long time to identify famous faces and to match unfamiliar faces. Nevertheless, he performs as accurately and quickly as controls at identifying inverted familiar and unfamiliar faces and can recognize famous faces from their external features. He also performs as accurately as controls at recognizing famous faces when fracturing conceals the configural information in the face. He shows evidence of impaired global processing but normal local processing of Navon figures. This case appears to reflect the clearest example yet of an acquired prosopagnosic patient whose familiar face recognition deficit is caused by a severe configural processing deficit in the absence of any problems in featural processing. These preserved featural skills together with apparently intact visual imagery for faces allow him to identify a surprisingly large number of famous faces when unlimited time is available. The theoretical implications of this pattern of performance for understanding the nature of acquired prosopagnosia are discussed.DY, Avery Braun, Jacob Waite, and Nadine Wanke, Bruno Rossion, Thomas Busigny and the grant awarded by AJ by the Experimental Psychology Society (EPS

Disfluency in dialogue:an intentional signal from the speaker?

Disfluency is a characteristic feature of spontaneous human speech, commonly seen as a consequence of problems with production. However, the question remains open as to why speakers are disfluent: Is it a mechanical by-product of planning difficulty, or do speakers use disfluency in dialogue to manage listeners' expectations? To address this question, we present two experiments investigating the production of disfluency in monologue and dialogue situations. Dialogue affected the linguistic choices made by participants, who aligned on referring expressions by choosing less frequent names for ambiguous images where those names had previously been mentioned. However, participants were no more disfluent in dialogue than in monologue situations, and the distribution of types of disfluency used remained constant. Our evidence rules out at least a straightforward interpretation of the view that disfluencies are an intentional signal in dialogue. © 2012 Psychonomic Society, Inc

Construction of probabilistic event trees for eruption forecasting at Sinabung volcano, Indonesia 2013-14

Eruptions of Sinabung volcano, Indonesia have been ongoing since 2013. Since that time, the character of eruptions has changed, from phreatic to phreatomagmatic to magmatic explosive eruptions, and from production of a lava dome that collapsed to a subsequent thick lava flow that slowly ceased to be active, and later, to a new lava dome. As the eruption progressed, event trees were constructed to forecast eruptive behavior six times, with forecast windows that ranged from 2. weeks to 1. year: November 7-10, December 12-14, and December 27, 2013; and January 9-10, May 13, and October 7, 2014. These event trees were successful in helping to frame the forecast scenarios, to collate current monitoring information, and to document outstanding questions and unknowns. The highest probability forecasts closely matched outcomes of eruption size (including extrusion of the first dome), production of pyroclastic density currents, and pyroclastic density current runout distances. Events assigned low probabilities also occurred, including total collapse of the lava dome in January 2014 and production of a small blast pyroclastic density current in February 2014

The need for multidisciplinarity in specialist training to optimize future patient care

Harmonious interactions between radiation, medical, interventional and surgical oncologists, as well as other members of multidisciplinary teams, are essential for the optimization of patient care in oncology. This multidisciplinary approach is particularly important in the current landscape, in which standard-of-care approaches to cancer treatment are evolving towards highly targeted treatments, precise image guidance and personalized cancer therapy. Herein, we highlight the importance of multidisciplinarity and interdisciplinarity at all levels of clinical oncology training. Potential deficits in the current career development pathways and suggested strategies to broaden clinical training and research are presented, with specific emphasis on the merits of trainee involvement in functional multidisciplinary teams. Finally, the importance of training in multidisciplinary research is discussed, with the expectation that this awareness will yield the most fertile ground for future discoveries. Our key message is for cancer professionals to fulfil their duty in ensuring that trainees appreciate the importance of multidisciplinary research and practice

Engineering the Controlled Assembly of Filamentous Injectisomes in E. coli K-12 for Protein Translocation into Mammalian Cells.

Bacterial pathogens containing type III protein secretion systems (T3SS) assemble large needle-like protein complexes in the bacterial envelope, called injectisomes, for translocation of protein effectors into host cells. The application of these molecular syringes for the injection of proteins into mammalian cells is hindered by their structural and genomic complexity, requiring multiple polypeptides encoded along with effectors in various transcriptional units (TUs) with intricate regulation. In this work, we have rationally designed the controlled expression of the filamentous injectisomes found in enteropathogenic Escherichia coli (EPEC) in the nonpathogenic strain E. coli K-12. All structural components of EPEC injectisomes, encoded in a genomic island called the locus of enterocyte effacement (LEE), were engineered in five TUs (eLEEs) excluding effectors, promoters and transcriptional regulators. These eLEEs were placed under the control of the IPTG-inducible promoter Ptac and integrated into specific chromosomal sites of E. coli K-12 using a marker-less strategy. The resulting strain, named synthetic injector E. coli (SIEC), assembles filamentous injectisomes similar to those in EPEC. SIEC injectisomes form pores in the host plasma membrane and are able to translocate T3-substrate proteins (e.g., translocated intimin receptor, Tir) into the cytoplasm of HeLa cells reproducing the phenotypes of intimate attachment and polymerization of actin-pedestals elicited by EPEC bacteria. Hence, SIEC strain allows the controlled expression of functional filamentous injectisomes for efficient translocation of proteins with T3S-signals into mammalian cells

Clinical management and research priorities for high-risk prostate cancer in the UK:meeting report of a multidisciplinary panel in conjunction with the NCRI Prostate Cancer Clinical Studies Localised Subgroup

The management of high-risk prostate cancer has become increasingly sophisticated, with refinements in radical therapy and the inclusion of adjuvant local and systemic therapies. Despite this, high-risk prostate cancer continues to have significant treatment failure rates, with progression to metastasis, castrate resistance and ultimately disease-specific death. In an effort to discuss the challenges in this field, the UK National Clinical Research Institute’s Prostate Cancer Clinical Studies localised subgroup convened a multidisciplinary national meeting in the autumn of 2014. The remit of the meeting was to debate and reach a consensus on the key clinical and research challenges in high-risk prostate cancer and to identify themes that the UK would be best placed to pursue to help improve outcomes. This report presents the outcome of those discussions and the key recommendations for future research in this highly heterogeneous disease entity