In silico screening of transaminase using semi-empirical QM/MM approach

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In silico screening of transaminase using semi-empirical QM/MM approach

Please click Additional Files below to see the full abstract

Heat-induced and spontaneous expression of Hsp70.1Luciferase transgene copies localized on Xp22 in female bovine cells

<p>Abstract</p> <p>Background</p> <p>Expression of several copies of the heat-inducible <it>Hsp70.1Luciferase </it>(<it>LUC</it>) transgene inserted at a single X chromosome locus of a bull (<it>Bos taurus</it>) was assessed in females after X-chromosome inactivation (XCI). Furthermore, impact of the chromosomal environment on the spontaneous expression of these transgene copies before XCI was studied during early development in embryos obtained after in vitro fertilization (IVF), when the locus was carried by the X chromosome inherited from the bull, and after somatic cell nuclear transfer (SCNT) cloning, when the locus could be carried by the inactive Xi or the active Xa chromosome in a female donor cell, or by the (active) X in a male donor cell.</p> <p>Findings</p> <p>Transgene copies were mapped to bovine Xp22. In XX^{<it>LUC </it>}female fibroblasts, i.e. after random XCI, the proportions of late-replicating inactive and early-replicating active X^{<it>LUC </it>}chromosomes were not biased and the proportion of cells displaying an increase in the level of immunostained luciferase protein after heat-shock induction was similar to that in male fibroblasts. Spontaneous transgene expression occurred at the 8-16-cell stage both in transgenic (female) embryos obtained after IVF and in male and female embryos obtained after SCNT.</p> <p>Conclusions</p> <p>The X^{<it>LUC </it>}chromosome is normally inactivated but at least part of the inactivated X-linked <it>Hsp70.1Luciferase </it>transgene copies remains heat-inducible after random XCI in somatic cells. Before XCI, the profile of the transgenes' spontaneous expression is independent of the epigenetic origin of the X^{<it>LUC </it>}chromosome since it is similar in IVF female, SCNT male and SCNT female embryos.</p

Privacy Considerations when Designing Social Network Systems to Support Successful Ageing

A number of interventions exist to support older adults in ageing well and these typically involve support for an active and sociable ageing process. We set out to examine the privacy implications of an intervention that would monitor mobility and share lifestyle and health data with a community of trusted others. We took a privacy-by-design approach to the system in the early stages of its development, working with older adults to firstly understand their networks of trust and secondly understand their privacy concerns should information be exchanged across that network. We used a Johari Windows framework in the thematic analysis of our data, concluding that the social sharing of information in later life carried significant risk. Our participants worried about the social signaling associated with data sharing and were cautious about a system that had the potential to disrupt established networks

Production of 3D printed scale models from microscope volume datasets for use in STEM education

Understanding the three-dimensional morphology of a biological sample at the microscopic level is a prerequisite to a functional understanding of cell biology, tissue development and growth. Images of microscopic samples obtained by compound light microscopy are customarily recorded and represented in two dimensions from a single orientation making it difficult to extrapolate 3D context from the 2D information. The commercialisation of fast, laser-based microscope systems (e.g. confocal, multi-photon or lightsheet microscopy) capable of generating volume datasets of microscopic samples through optical sectioning, coupled with advances in computer technology allowing accurate volume rendering of these datasets, have facilitated significant improvement in our 3D understanding of the microscopic world in virtual space. The advent of affordable 3D printing technology now offers the prospect of generating morphologically accurate, physical models from these microscope volume datasets for use in science education, outreach and engagement. 3D printed scale replicas will provide improved sensory perception, offering tactile as well as visual interaction, leading to improved understanding of structure function relationships. Here we present a technique to reliably generate detailed, physical 3D models from Z-stacks of optical sections from confocal and lightsheet microscopes using affordable, entry-level 3D printing technology. We use the technique to generate 3D printed models of a variety of different biological samples at a range of scales including pollen grains from two species of plant; blood cells from both human and earthworm species, a section of plant root; the compound eye of an ant; and a developing Zebrafish larva; all of which have been used in our teaching, engagement and outreach activities. Our methods can, in principle, be used to generate 3D printed models from microscope volume datasets of any small fluorescent or reflective samples

The color of support: The effect of sponsor–team visual congruence on sponsorship performance

© American Marketing Association 2019. Brand sponsorship connects brands with large, passionate audiences. The sponsorship literature emphasizes the importance of brand sponsor–team congruence; however, prior research has largely focused on the relevance of the brand to the sport or geographic area. This article offers the first real-world empirical investigation of the effects of visual congruence through color matching on sponsorship performance. A wide-scale study of 703 Major League Baseball fans’ evaluations of their team’s sponsors, merged with real stadium signage data, offers evidence of the benefits of visual congruence. Two experiments in the contexts of product packaging and online advertising provide converging evidence of the positive effects of created visual congruence on attitudes toward the sponsorship, brand attitudes, and intentions. Brands without an inherent match to a team can enjoy enhanced sponsorship benefits with little additional costs simply by adopting the team’s colors in visual displays. However, the viewer’s motivation (fan status), opportunity (fan exposure), and ability (lack of color blindness) to process visual congruence moderates its effectiveness. By using the proposed framework, managers can maximize the value of their sponsorship rights

Wellbeing while waiting evaluating social prescribing in CAMHS: study protocol for a hybrid type II implementation-effectiveness study

Background: Social prescribing is a mechanism of connecting patients with non-medical forms of support within the community and has been shown to improve mental health and wellbeing in adult populations. In the last few years, it has been used in child and youth settings with promising results. Currently, pathways are being developed for social prescribing in Child and Adolescent Mental Health Services (CAMHS) to support children and young people on treatment waiting lists. The Wellbeing While Waiting study will evaluate whether social prescribing benefits the mental health and wellbeing of children and young people. / Methods: This study utilises an observational, hybrid type II implementation-effectiveness design. Up to ten CAMHS who are developing social prescribing pathways as part of a programme run across England with support from the Social Prescribing Youth Network will participate. Outcomes for children and young people receiving social prescribing whilst on CAMHS waiting lists will be compared to a control group recruited prior to the pathway roll-out. Questionnaire data will be collected at baseline, 3 months and 6 months. Primary outcomes for children and young people are mental health symptoms (including anxiety, depression, stress, emotional and behavioural difficulties). Secondary outcomes include: loneliness, resilience, happiness, whether life is worthwhile, life satisfaction, and service use. An implementation strand using questionnaires and interviews will explore the acceptability, feasibility, and suitability of the pathway, potential mechanisms of action and their moderating effects on the outcomes of interest, as well as the perceived impact of social prescribing. Questionnaire data will be analysed mainly using difference-in-differences or controlled interrupted time series analysis. Interview data will be analysed using reflexive thematic analysis. / Discussion: The Wellbeing While Waiting study will provide the first rigorous evidence of the impact of social prescribing for children and young people on waiting lists for mental health treatment. Findings will help inform the prioritisation, commissioning, and running of social prescribing in other CAMHS. To maximise impact, findings will be available on the study website (https://sbbresearch.org) and disseminated via national and international networks

Lyman Continuum Escape Fraction of Star-forming Dwarf Galaxies at z ~ 1

To date, no direct detection of Lyman continuum emission has been measured for intermediate-redshift (z ~ 1) star-forming galaxies. We combine Hubble Space Telescope grism spectroscopy with GALEX UV and ground-based optical imaging to extend the search for escaping Lyman continuum to a large (~600) sample of z ~ 1 low-mass log(M)≃ 9.3 M_☉), moderately star-forming (ψ ≾ 10M_☉ yr^(−1)) galaxies selected initially on Hα emission. The characteristic escape fraction of LyC from star-forming galaxies (SFGs) that populate this parameter space remains weakly constrained by previous surveys, but these faint (sub-Lsstarf) SFGs are assumed to play a significant role in the reionization of neutral hydrogen in the intergalactic medium (IGM) at high redshift z > 6. We do not make an unambiguous detection of escaping LyC radiation from this z ~ 1 sample, individual non-detections to constrain the absolute Lyman continuum escape fraction, f_(esc) 200Å), which are thought to be close analogs of high redshift sources of reionization. For reference, we also present an emissivity-weighted escape fraction that is useful for measuring the general contribution SFGs to the ionizing UV background. In the discussion, we consider the implications of these intermediate redshift constraints for the reionization of hydrogen in the IGM at high (z > 6) redshift. If we assume our z ~ 1 SFGs, for which we measure this emissivity-weighted f_(esc), are analogs to the high redshift sources of reionization, we find it is difficult to reconcile reionization by faint (M}_(UV) ≾-13) SFGs with a low escape fraction (f_(esc) < 3%), with constraints from independent high redshift observations. If f_(esc) evolves with redshift, reionization by SFGs may be consistent with observations from Planck