Experimentally induced pain does not influence updating of peripersonal space and body representations following tool-use

This is the final version. Available from the publisher via the DOI in this record.The data is available on the Open Science Framework. URL: https://osf.io/4v938/. DOI: 10.17605/OSF.IO/4V938.Representations of the body and peripersonal space can be distorted for people with some chronic pain conditions. Experimental pain induction can give rise to similar, but transient distortions in healthy individuals. However, spatial and bodily representations are dynamic, and constantly update as we interact with objects in our environment. It is unclear whether induced pain disrupts the mechanisms involved in updating these representations. In the present study, we sought to investigate the effect of induced pain on the updating of peripersonal space and body representations during and following tool-use. We compared performance under three conditions (pain, active placebo, neutral) on a visuotactile crossmodal congruency task and a tactile distance judgement task to measure updating of peripersonal space and body representations, respectively. Consistent with previous findings, the difference in crossmodal interference from visual distractors in the same compared to opposite visual field to the tactile target was less when tools were crossed than uncrossed. This suggests an extension of peripersonal space to incorporate the tips of the tools. Also consistent with previous findings, estimates of the felt tactile distance judgements decreased after active tool-use. In contrast to our predictions, however, we found no evidence that pain interfered with performance on either task when compared to the control conditions. Our findings suggest that the updating of peripersonal space and body representations is not disrupted by induced pain. That is, experiencing acute pain does not give rise to distorted representations of the body and peripersonal space that can be present in people with chronic pain conditions.Medical Research Council (MRC

Gain of Function Analysis Reveals Non-Redundant Roles for the Yersinia pestis Type III Secretion System Effectors YopJ, YopT, and YpkA [preprint]

Virulence of Yersinia pestis in mammals requires the type III secretion system, which delivers seven effector proteins into the cytoplasm of host cells to undermine immune responses. All seven of these effectors are conserved across Y. pestis strains, but three -- YopJ, YopT, and YpkA -- are apparently dispensable for virulence. Some degree of functional redundancy between effector proteins would explain both observations. Here, we use a combinatorial genetic approach to define the minimal subset of effectors required for full virulence in mice following subcutaneous infection. We found that a Y. pestis strain lacking YopJ, YopT, and YpkA is attenuated for virulence in mice, and that addition of any one of these effectors to this strain increases lethality significantly. YopJ, YopT, and YpkA likely contribute to virulence via distinct mechanisms. YopJ is uniquely able to cause macrophage cell death in vitro and to suppress accumulation of inflammatory cells to foci of bacterial growth in deep tissue, whereas YopT and YpkA cannot. The synthetic phenotypes that emerge when YopJ, YopT, and YpkA are removed in combination provide evidence that each enhances Y. pestis virulence, and that YopT and YpkA act through a mechanism distinct from that of YopJ

Separation and identification of dominant mechanisms in double photoionization

Double photoionization by a single photon is often discussed in terms of two contributing mechanisms, {\it knock-out} (two-step-one) and {\it shake-off} with the latter being a pure quantum effect. It is shown that a quasi-classical description of knock-out and a simple quantum calculation of shake-off provides a clear separation of the mechanisms and facilitates their calculation considerably. The relevance of each mechanism at different photon energies is quantified for helium. Photoionization ratios, integral and singly differential cross sections obtained by us are in excellent agreement with benchmark experimental data and recent theoretical results.Comment: 4 pages, 5 figure

Genome-wide mutant fitness profiling identifies nutritional requirements for optimal growth of Yersinia pestis in deep tissue

Rapid growth in deep tissue is essential to the high virulence of Yersinia pestis, causative agent of plague. To better understand the mechanisms underlying this unusual ability, we used transposon mutagenesis and high-throughput sequencing (Tn-seq) to systematically probe the Y. pestis genome for elements contributing to fitness during infection. More than a million independent insertion mutants representing nearly 200,000 unique genotypes were generated in fully virulent Y. pestis. Each mutant in the library was assayed for its ability to proliferate in vitro on rich medium and in mice following intravenous injection. Virtually all genes previously established to contribute to virulence following intravenous infection showed significant fitness defects, with the exception of genes for yersiniabactin biosynthesis, which were masked by strong intercellular complementation effects. We also identified more than 30 genes with roles in nutrient acquisition and metabolism as experiencing strong selection during infection. Many of these genes had not previously been implicated in Y. pestis virulence. We further examined the fitness defects of strains carrying mutations in two such genes-encoding a branched-chain amino acid importer (brnQ) and a glucose importer (ptsG)-both in vivo and in a novel defined synthetic growth medium with nutrient concentrations matching those in serum. Our findings suggest that diverse nutrient limitations in deep tissue play a more important role in controlling bacterial infection than has heretofore been appreciated. Because much is known about Y. pestis pathogenesis, this study also serves as a test case that assesses the ability of Tn-seq to detect virulence genes. IMPORTANCE: Our understanding of the functions required by bacteria to grow in deep tissues is limited, in part because most growth studies of pathogenic bacteria are conducted on laboratory media that do not reflect conditions prevailing in infected animal tissues. Improving our knowledge of this aspect of bacterial biology is important as a potential pathway to the development of novel therapeutics. Yersinia pestis, the plague bacterium, is highly virulent due to its rapid dissemination and growth in deep tissues, making it a good model for discovering bacterial adaptations that promote rapid growth during infection. Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of Y. pestis in vivo that were not previously known to be important. Most of these functions are needed to acquire or synthesize nutrients. Interference with these critical nutrient acquisition pathways may be an effective strategy for designing novel antibiotics and vaccines

Using Immersive Virtual Reality to Examine How Visual and Tactile Cues Drive the Material-Weight Illusion

This is the final version. Available on open access from Springer via the DOI in this recordAvailability of Data and Materials: All materials and data are available on the Open Science Framework (https://osf.io/7k548/).The material-weight illusion (MWI) demonstrates how our past experience with material and weight can create expectations that influence the perceived heaviness of an object. Here we used mixed-reality to place touch and vision in conflict, to investigate whether the modality through which materials are presented to a lifter could influence the top-down perceptual processes driving the MWI. University students lifted equally-weighted polystyrene, cork and granite cubes whilst viewing computer-generated images of the cubes in virtual reality (VR). This allowed the visual and tactile material cues to be altered, whilst all other object properties were kept constant. Representation of the objects' material in VR was manipulated to create four sensory conditions: visual-tactile matched, visual-tactile mismatched, visual differences only and tactile differences only. A robust MWI was induced across all sensory conditions, whereby the polystyrene object felt heavier than the granite object. The strength of the MWI differed across conditions, with tactile material cues having a stronger influence on perceived heaviness than visual material cues. We discuss how these results suggest a mechanism whereby multisensory integration directly impacts how top-down processes shape perception.Engineering and Physical Sciences Research Council (EPSRC

Genome-wide transcriptional response of an avian pathogenic Escherichia coli (APEC) pst mutant

<p>Abstract</p> <p>Background</p> <p>Avian pathogenic <it>E</it>. <it>coli </it>(APEC) are associated with extraintestinal diseases in poultry. The <it>pstSCAB</it>-<it>phoU </it>operon belongs to the Pho regulon and encodes the phosphate specific transport (Pst) system. A functional Pst system is required for full virulence in APEC and other bacteria and contributes to resistance of APEC to serum, to cationic antimicrobial peptides and acid shock. The global mechanisms contributing to the attenuation and decreased resistance of the APEC <it>pst </it>mutant to environmental stresses have not been investigated at the transcriptional level. To determine the global effect of a <it>pst </it>mutation on gene expression, we compared the transcriptomes of APEC strain χ7122 and its isogenic <it>pst </it>mutant (K3) grown in phosphate-rich medium.</p> <p>Results</p> <p>Overall, 470 genes were differentially expressed by at least 1.5-fold. Interestingly, the <it>pst </it>mutant not only induced systems involved in phosphate acquisition and metabolism, despite phosphate availability, but also modulated stress response mechanisms. Indeed, transcriptional changes in genes associated with the general stress responses, including the oxidative stress response were among the major differences observed. Accordingly, the K3 strain was less resistant to reactive oxygen species (ROS) than the wild-type strain. In addition, the <it>pst </it>mutant demonstrated reduced expression of genes involved in lipopolysaccharide modifications and coding for cell surface components such as type 1 and F9 fimbriae. Phenotypic tests also established that the <it>pst </it>mutant was impaired in its capacity to produce type 1 fimbriae, as demonstrated by western blotting and agglutination of yeast cells, when compared to wild-type APEC strain χ7122.</p> <p>Conclusion</p> <p>Overall, our data elucidated the effects of a <it>pst </it>mutation on the transcriptional response, and further support the role of the Pho regulon as part of a complex network contributing to phosphate homeostasis, adaptive stress responses, and <it>E. coli </it>virulence.</p

Altered updating of bodily and spatial representations following tool-use in complex regional pain syndrome

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.  Distorted representations of the body and peripersonal space are common in Complex Regional Pain Syndrome (CRPS), and might modulate its symptoms (e.g. asymmetric limb temperature). In pain-free people, such representations are malleable, and update when we interact with objects in our environment (e.g. during tool-use). Distortions are also common after immobilisation, but quickly normalise once movement is regained. We tested the hypothesis that people with CRPS have problems updating bodily and spatial representations, which contributes to the maintenance of their distorted representations by preventing normalization. We also explored spatially defined modulations of hand temperature asymmetries, and any influence of updating bodily and spatial representations on this effect. Thirty-six people with unilateral CRPS (18 upper limb, 18 lower limb) and 36 pain-free controls completed tool-use tasks considered to alter body and peripersonal space representations (measured using tactile distance judgements and a visuotactile crossmodal congruency task, respectively). We also tested how the arrangement (crossed, uncrossed) of the hands and tools affected hand temperature. In upper limb CRPS the non-affected arm representation updated normally, but the affected arm representation updated in the opposite to normal direction. A similar pattern was seen in lower limbs CRPS, although not significant. Furthermore, people with CRPS showed more pronounced updating of peripersonal space than the controls. We did not observe any modulation of hand temperature asymmetries by the arrangement of hands or tools. Our findings show enhanced malleability of bodily and spatial representations in CRPS, which may suggest that central mechanisms are altered in this condition.Medical Research Counci