465 research outputs found

    Pathogenic Adaptation of Intracellular Bacteria by Rewiring a Cis-Regulatory Input Function

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    The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones

    Industrial work placement in higher education: a study of civil engineering student engagement

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    For civil engineering undergraduates, the opportunity to spend a period of time in formal industrial work placement provides an invaluable learning experience. This paper reviews student engagement with short-term industrial placement and provides analysis of questionnaires (n=174) returned by undergraduates studying civil engineering at four Higher Education Institutes (HEI’s) in the West of Scotland. The data captures industrial placement statistics, employability skill-sets and presents brief testimonies from students. Whilst the journey to becoming a professional civil engineer is undoubtedly enhanced by short-term placement clear opportunities exist for HEI’s to affect and change existing pedagogical discourse. Commentary is likely to resonate beyond civil engineering and serve as a timely reminder of the need to re-invigorate academia / industry curriculum partnerships

    Where do graduates Develop their Enterprise Skills? The Value of the Contribution of Higher Education Institutions’ Context

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    This study investigates the value of the contribution of HEIs’ context in developing graduates enterprise skills. HEIs are under pressure to develop more enterprising graduates, particularly with the increasing numbers of graduates seeking employment and the growing dissatisfaction of employers. This study explores where graduates develop enterprise skills through investigating the impact of HE and employment contexts on their development. The paper draws on a qualitative study in the social constructionist paradigm within the pharmacy context, where interviews were conducted with pharmacy academics and employers. Results show that ability to demonstrate skills in one context does not necessarily mean ability to demonstrate them in another since the development and demonstration of enterprise skills is impacted by the contexts in which they are developed and demonstrated. The study adds value by highlighting the significant role of both HE and employment contexts in developing enterprise skills, while emphasising that these skills become more transferable through exposure to more contexts

    DNA Synthesis Generates Terminal Duplications That Seal End-to-End Chromosome Fusions

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    End-to-end chromosome fusions that occur in the context of telomerase deficiency can trigger genomic duplications. For over 70 years these duplications have been attributed solely to Breakage-Fusion-Bridge cycles. To test this hypothesis, we examined end-to-end fusions isolated from C. elegans telomere replication mutants. Genome level rearrangements revealed fused chromosome ends possessing interrupted terminal duplications accompanied by template switching events. These features are very similar to disease-associated duplications of interstitial segments of the human genome. A model termed Fork Stalling and Template Switching has been proposed previously to explain such duplications, where promiscuous replication of large, non-contiguous segments of the genome occurs. Thus, a DNA synthesis-based process may create duplications that seal end-to-end fusions, in the absence of Breakage-Fusion-Bridge cycles

    Structural relaxation in a system of dumbbell molecules

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    The interaction-site-density-fluctuation correlators, the dipole-relaxation functions, and the mean-squared displacements of a system of symmetric dumbbells of fused hard spheres are calculated for two representative elongations of the molecules within the mode-coupling theory for the evolution of glassy dynamics. For large elongations, universal relaxation laws for states near the glass transition are valid for parameters and time intervals similar to the ones found for the hard-sphere system. Rotation-translation coupling leads to an enlarged crossover interval for the mean-squared displacement of the constituent atoms between the end of the von Schweidler regime and the beginning of the diffusion process. For small elongations, the superposition principle for the reorientational α\alpha-process is violated for parameters and time intervals of interest for data analysis, and there is a strong breaking of the coupling of the α\alpha-relaxation scale for the diffusion process with that for representative density fluctuations and for dipole reorientations.Comment: 15 pages, 14 figures, Phys. Rev. E in pres

    Collaboration between Science and Religious Education teachers in Scottish Secondary schools

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    The article reports on quantitative research that examines: (1) the current practice in collaboration; and (2) potential for collaboration between Science and Religious Education teachers in a large sample of Scottish secondary schools. The authors adopt and adapt three models (conflict; concordat and consonance) to interrogate the relationship between science and religion (and the perceived relation between these two subjects in schools) (Astley and Francis 2010). The findings indicate that there is evidence of limited collaboration and, in a few cases, a dismissive attitude towards collaboration (conflict and concordat and very weak consonance). There is, however, evidence of a genuine aspiration for greater collaboration among many teachers (moving towards a more robust consonance model). The article concludes by discussing a number of key factors that must be realised for this greater collaboration to be enacted

    End Joining at Caenorhabditis elegans Telomeres

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    Critically shortened telomeres can be subjected to DNA repair events that generate end-to-end chromosome fusions. The resulting dicentric chromosomes can enter breakage–fusion–bridge cycles, thereby impeding elucidation of the structures of the initial fusion events and a mechanistic understanding of their genesis. Current models for the molecular basis of fusion of critically shortened, uncapped telomeres rely on PCR assays that typically capture fusion breakpoints created by direct ligation of chromosome ends. Here we use independent approaches that rely on distinctive features of Caenorhabditis elegans to study the frequency of direct end-to-end chromosome fusion in telomerase mutants: (1) holocentric chromosomes that allow for genetic isolation of stable end-to-end fusions and (2) unique subtelomeric sequences that allow for thorough PCR analysis of samples of genomic DNA harboring multiple end-to-end fusions. Surprisingly, only a minority of end-to-end fusion events resulted from direct end joining with no additional genome rearrangements. We also demonstrate that deficiency for the C. elegans Ku DNA repair heterodimer does not affect telomere length or cause synthetic effects in the absence of telomerase

    COIVF-9 %Ob 6Y-- N EAR-N ET-SHAPE FABRICATION BY FORCED-FLOW, THERMAL-G RAD1 ENT CVI*

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    Forced-flow, thermal gradient chemical vapor infiltration (FCVI) has been developed for the rapid densification of ceramic matrix composites. For preforms of >3 mm thickness FCVl can produce a near-net-shape part in less than one day as opposed to isothermal, isobaric CVI which requires several weeks to densify such a component. Efforts at ORNL and elsewhere have resulted in capability to produce prototypical thick-walled heat exchanger tubes and turbine disk blanks. This paper will review recent modeling and experimental efforts related to the FCVl of cylindrical forms
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