Burkholderia thailandensis strain E555 is a surrogate for the investigation of Burkholderia pseudomallei replication and survival in macrophages

This is the final version. Available on open access from BMC via the DOI in this recordBackground: Burkholderia pseudomallei is a human pathogen causing severe infections in tropical and subtropical regions and is classified as a bio-threat agent. B. thailandensis strain E264 has been proposed as less pathogenic surrogate for understanding the interactions of B. pseudomallei with host cells. Results: We show that, unlike B. thailandensis strain E264, the pattern of growth of B. thailandensis strain E555 in macrophages is similar to that of B. pseudomallei. We have genome sequenced B. thailandensis strain E555 and using the annotated sequence identified genes and proteins up-regulated during infection. Changes in gene expression identified more of the known B. pseudomallei virulence factors than changes in protein levels and used together we identified 16% of the currently known B. pseudomallei virulence factors. These findings demonstrate the utility of B. thailandensis strain E555 to study virulence of B. pseudomallei. Conclusions: A weakness of studies using B. thailandensis as a surrogate for B. pseudomallei is that the strains used replicate at a slower rate in infected cells. We show that the pattern of growth of B. thailandensis strain E555 in macrophages closely mirrors that of B. pseudomallei. Using this infection model we have shown that virulence factors of B. pseudomallei can be identified as genes or proteins whose expression is elevated on the infection of macrophages. This finding confirms the utility of B. thailandensis strain E555 as a surrogate for B. pseudomallei and this strain should be used for future studies on virulence mechanisms.United Kingdom Ministry of Defens

The Culture Environment Influences Both Gene Regulation and Phenotypic Heterogeneity in Escherichia coli

This is the final version of the article. Available from Frontiers Media via the DOI in this record.Microorganisms shape the composition of the medium they are growing in, which in turn has profound consequences on the reprogramming of the population gene-expression profile. In this paper, we investigate the progressive changes in pH and sugar availability in the medium of a growing Escherichia coli (E. coli) culture. We show how these changes have an effect on both the cellular heterogeneity within the microbial community and the gene-expression profile of the microbial population. We measure the changes in gene-expression as E. coli moves from lag, to exponential, and finally into stationary phase. We found that pathways linked to the changes in the medium composition such as ribosomal, tricarboxylic acid cycle (TCA), transport, and metabolism pathways are strongly regulated during the different growth phases. In order to quantify the corresponding temporal changes in the population heterogeneity, we measure the fraction of E. coli persisters surviving different antibiotic treatments during the various phases of growth. We show that the composition of the medium in which β-lactams or quinolones, but not aminoglycosides, are dissolved strongly affects the measured phenotypic heterogeneity within the culture. Our findings contribute to a better understanding on how the composition of the culture medium influences both the reprogramming in the population gene-expression and the emergence of phenotypic variants.This work was supported by a Royal Society Research Grant (RG140203), a Wellcome Trust Strategic Seed Corn Fund (WT097835/Z/11/Z), and a start up Grant from the University of Exeter awarded to SP. AS acknowledges support from the BBSRC through a SWBio-DTP studentship (BB/M009122/1). KP, KM, and PO would like to acknowledge support from the following awards: Wellcome Trust Institutional Strategic Support Fund (WT097835MF), Wellcome Trust Multi User Equipment Award (WT101650MA), and Medical Research Council Clinical Infrastructure Funding (MR/M008924/1). This work was partly supported by BBSRC award BB/1024631/1 to RT

Chess databases as a research vehicle in psychology : modeling large data

The game of chess has often been used for psychological investigations, particularly in cognitive science. The clear-cut rules and well-defined environment of chess provide a model for investigations of basic cognitive processes, such as perception, memory, and problem solving, while the precise rating system for the measurement of skill has enabled investigations of individual differences and expertise-related effects. In the present study, we focus on another appealing feature of chess—namely, the large archive databases associated with the game. The German national chess database presented in this study represents a fruitful ground for the investigation of multiple longitudinal research questions, since it collects the data of over 130,000 players and spans over 25 years. The German chess database collects the data of all players, including hobby players, and all tournaments played. This results in a rich and complete collection of the skill, age, and activity of the whole population of chess players in Germany. The database therefore complements the commonly used expertise approach in cognitive science by opening up new possibilities for the investigation of multiple factors that underlie expertise and skill acquisition. Since large datasets are not common in psychology, their introduction also raises the question of optimal and efficient statistical analysis. We offer the database for download and illustrate how it can be used by providing concrete examples and a step-by-step tutorial using different statistical analyses on a range of topics, including skill development over the lifetime, birth cohort effects, effects of activity and inactivity on skill, and gender differences

Discovery of new methylation markers to improve screening for cervical intraepithelial neoplasia grade 2/3

Background: Assessment of DNA promoter methylation markers in cervical scrapings for the detection of cervical intraepithelial neoplasia (CIN) and cervical cancer is feasible, but finding methylation markers with both high sensitivity as well as high specificity remains a challenge. In this study, we aimed to identify new methylation markers for the detection of high-grade CIN (CIN2/3 or worse, CIN2+) by using innovative genome-wide methylation analysis (MethylCap-seq). We focused on diagnostic performance of methylation markers with high sensitivity and high specificity considering any methylation level as positive. Results: MethylCap-seq of normal cervices and CIN2/3 revealed 176 differentially methylated regions (DMRs) comprising 164 genes. After verification and validation of the 15 best discriminating genes with methylation-specific PCR (MSP), 9 genes showed significant differential methylation in an independent cohort of normal cervices versus CIN2/3 lesions (p < 0.05). For further diagnostic evaluation, these 9 markers were tested with quantitative MSP (QMSP) in cervical scrapings from 2 cohorts: (1) cervical carcinoma versus healthy controls and (2) patients referred from population-based screening with an abnormal Pap smear in whom also HPV status was determined. Methylation levels of 8/9 genes were significantly higher in carcinoma compared to normal scrapings. For all 8 genes, methylation levels increased with the severity of the underlying histological lesion in scrapings from patients referred with an abnormal Pap smear. In addition, the diagnostic performance was investigated, using these 8 new genes and 4 genes (previously identified by our group: C13ORF18, JAM3, EPB41L3, and TERT). In a triage setting (after a positive Pap smear), sensitivity for CIN2+ of the best combination of genes (C13ORF18/JAM3/ANKRD18CP) (74 %) was comparable to hrHPV testing (79 %), while specificity was significantly higher (76 % versus 42 %, p <= 0.05). In addition, in hrHPV-positive scrapings, sensitivity and specificity for CIN2+ of this best-performing combination was comparable to the population referred with abnormal Pap smear. Conclusions: We identified new CIN2/3-specific methylation markers using genome-wide DNA methylation analysis. The diagnostic performance of our new methylation panel shows higher specificity, which should result in prevention of unnecessary colposcopies for women referred with abnormal cytology. In addition, these newly found markers might be applied as a triage test in hrHPV-positive women from population-based screening. The next step before implementation in primary screening programs will be validation in population-based cohorts

Spectral compression of single photons

Photons are critical to quantum technologies since they can be used for virtually all quantum information tasks: in quantum metrology, as the information carrier in photonic quantum computation, as a mediator in hybrid systems, and to establish long distance networks. The physical characteristics of photons in these applications differ drastically; spectral bandwidths span 12 orders of magnitude from 50 THz for quantum-optical coherence tomography to 50 Hz for certain quantum memories. Combining these technologies requires coherent interfaces that reversibly map centre frequencies and bandwidths of photons to avoid excessive loss. Here we demonstrate bandwidth compression of single photons by a factor 40 and tunability over a range 70 times that bandwidth via sum-frequency generation with chirped laser pulses. This constitutes a time-to-frequency interface for light capable of converting time-bin to colour entanglement and enables ultrafast timing measurements. It is a step toward arbitrary waveform generation for single and entangled photons.Comment: 6 pages (4 figures) + 6 pages (3 figures

Affective Influences without Approach-Avoidance Actions: On the Congruence Between Valence and Stimulus-Response Mappings

The valence of stimuli can influence performance in the spatial stimulus–response compatibility task, but this observation could arise from the process of selecting responses or selecting stimulus–response mappings. The response-selection account proposes that spatial compatible and incompatible keypress responses serve as approaching and avoiding actions to a valenced target. The mapping-selection account suggests that there is congruence between stimulus valence and stimulus–response mappings; positive-compatible/negative-incompatible is more congruent than negative-compatible/positive-incompatible. Whereas affective valence was part of the target stimuli to which participants responded in previous studies, the present study isolated affective valence from the target by presenting an additional mapping cue separately from the target, so that spatially compatible and incompatible keypress responses could no longer serve as approaching and avoiding actions to valenced target stimuli. The present results revealed that responses were still faster when positive and negative mapping cues were assigned to the spatially compatible and incompatible mappings than when the assignment was reversed. The finding supports the mapping-selection account, indicating that positive and negative cues influence performance without approach–avoidance actions to valenced stimuli. The experiment provides important implications as to how tasks are represented and are dependent on affective processing

Evidence for distinct coastal and offshore communities of bottlenose dolphins in the north east Atlantic.

Bottlenose dolphin stock structure in the northeast Atlantic remains poorly understood. However, fine scale photo-id data have shown that populations can comprise multiple overlapping social communities. These social communities form structural elements of bottlenose dolphin (Tursiops truncatus) [corrected] populations, reflecting specific ecological and behavioural adaptations to local habitats. We investigated the social structure of bottlenose dolphins in the waters of northwest Ireland and present evidence for distinct inshore and offshore social communities. Individuals of the inshore community had a coastal distribution restricted to waters within 3 km from shore. These animals exhibited a cohesive, fission-fusion social organisation, with repeated resightings within the research area, within a larger coastal home range. The offshore community comprised one or more distinct groups, found significantly further offshore (>4 km) than the inshore animals. In addition, dorsal fin scarring patterns differed significantly between inshore and offshore communities with individuals of the offshore community having more distinctly marked dorsal fins. Specifically, almost half of the individuals in the offshore community (48%) had characteristic stereotyped damage to the tip of the dorsal fin, rarely recorded in the inshore community (7%). We propose that this characteristic is likely due to interactions with pelagic fisheries. Social segregation and scarring differences found here indicate that the distinct communities are likely to be spatially and behaviourally segregated. Together with recent genetic evidence of distinct offshore and coastal population structures, this provides evidence for bottlenose dolphin inshore/offshore community differentiation in the northeast Atlantic. We recommend that social communities should be considered as fundamental units for the management and conservation of bottlenose dolphins and their habitat specialisations

Notch in OEC development

Olfactory ensheathing cells (OECs) are a unique glial population found in both the peripheral and central nervous system: they ensheath bundles of unmyelinated olfactory axons from their peripheral origin in the olfactory epithelium to their central synaptic targets in the glomerular layer of the olfactory bulb. Like all other peripheral glia (Schwann cells, satellite glia, enteric glia), OECs are derived from the embryonic neural crest. However, in contrast to Schwann cells, whose development has been extensively characterised, relatively little is known about their normal development in vivo. In the Schwann cell lineage, the transition from multipotent Schwann cell precursor to immature Schwann cell is promoted by canonical Notch signalling. Here, in situ hybridisation and immunohistochemistry data from chicken, mouse and human embryos are presented that suggest a canonical Notch-mediated transition also occurs during OEC development.S.R.M. was supported by a PhD research studentship from the Anatomical Society, with additional funding from the Cambridge Philosophical Society. S.P. was supported by the Wellcome Trust (PhD Studentship 102453/Z/13/Z) and the Cambridge Commonwealth Trust. C.B. was funded by Wellcome Trust Program grant 091119/Z/10/Z to Kristjan Jessen and Rhona Mirsky (University College London, London, UK). S.R.W.S. was supported by the European Union (DDPDGENES). Thanks to Perrine Barraud (University of Cambridge, Cambridge, UK) for providing mouse cDNA, to Nicolas Daudet (University College London, London, UK) for providing chicken plasmids, and to Roger Barker (University of Cambridge, Cambridge, UK) for his support in obtaining human foetal tissue.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley

Standardizing estimates of the Plasmodium falciparum parasite rate

<p>Abstract</p> <p>Background</p> <p>The <it>Plasmodium falciparum </it>parasite rate (PfPR) is a commonly reported index of malaria transmission intensity. PfPR rises after birth to a plateau before declining in older children and adults. Studies of populations with different age ranges generally report average PfPR, so age is an important source of heterogeneity in reported PfPR data. This confounds simple comparisons of PfPR surveys conducted at different times or places.</p> <p>Methods</p> <p>Several algorithms for standardizing PfPR were developed using 21 studies that stratify in detail PfPR by age. An additional 121 studies were found that recorded PfPR from the same population over at least two different age ranges; these paired estimates were used to evaluate these algorithms. The best algorithm was judged to be the one that described most of the variance when converting the PfPR pairs from one age-range to another.</p> <p>Results</p> <p>The analysis suggests that the relationship between PfPR and age is predictable across the observed range of malaria endemicity. PfPR reaches a peak after about two years and remains fairly constant in older children until age ten before declining throughout adolescence and adulthood. The PfPR pairs were poorly correlated; using one to predict the other would explain only 5% of the total variance. By contrast, the PfPR predicted by the best algorithm explained 72% of the variance.</p> <p>Conclusion</p> <p>The PfPR in older children is useful for standardization because it has good biological, epidemiological and statistical properties. It is also historically consistent with the classical categories of hypoendemic, mesoendemic and hyperendemic malaria. This algorithm provides a reliable method for standardizing PfPR for the purposes of comparing studies and mapping malaria endemicity. The scripts for doing so are freely available to all.</p

The decline in paediatric malaria admissions on the coast of Kenya

<p>Abstract</p> <p>Background</p> <p>There is only limited information on the health impact of expanded coverage of malaria control and preventative strategies in Africa.</p> <p>Methods</p> <p>Paediatric admission data were assembled over 8.25 years from three District Hospitals; Kilifi, Msambweni and Malindi, situated along the Kenyan Coast. Trends in monthly malaria admissions between January 1999 and March 2007 were analysed using several time-series models that adjusted for monthly non-malaria admission rates and the seasonality and trends in rainfall.</p> <p>Results</p> <p>Since January 1999 paediatric malaria admissions have significantly declined at all hospitals. This trend was observed against a background of rising or constant non-malaria admissions and unaffected by long-term rainfall throughout the surveillance period. By March 2007 the estimated proportional decline in malaria cases was 63% in Kilifi, 53% in Kwale and 28% in Malindi. Time-series models strongly suggest that the observed decline in malaria admissions was a result of malaria-specific control efforts in the hospital catchment areas.</p> <p>Conclusion</p> <p>This study provides evidence of a changing disease burden on the Kenyan coast and that the most parsimonious explanation is an expansion in the coverage of interventions such as the use of insecticide-treated nets and the availability of anti-malarial medicines. While specific attribution to intervention coverage cannot be computed what is clear is that this area of Kenya is experiencing a malaria epidemiological transition.</p