Novel mRNA-specific effects of ribosome drop-off on translation rate and polysome profile

IS and MCR were supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (http://www.bbsrc.ac.uk) BB/N017161/1. IS was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (http://www.bbsrc.ac.uk) BB/I020926/1. PB and MCR were supported by the Scottish Universities Life Sciences Alliance (SULSA) (http://www.sulsa.ac.uk). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

The effects of psilocybin on cognitive and emotional functions in healthy participants : Results from a phase 1, randomised, placebo-controlled trial involving simultaneous psilocybin administration and preparation

Background: Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin's effects on cognitive function have not been widely or systematically studied. Aim: The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring. Methods: In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants (n=89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support - each participant having an assigned, dedicated therapist available throughout the session. Results: In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores. Conclusions: These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing.Peer reviewe

Identifying the science and technology dimensions of emerging public policy issues through horizon scanning

Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security.Public policy requires public support, which in turn implies a need to enable the public not just to understand policy but also to be engaged in its development. Where complex science and technology issues are involved in policy making, this takes time, so it is important to identify emerging issues of this type and prepare engagement plans. In our horizon scanning exercise, we used a modified Delphi technique [1]. A wide group of people with interests in the science and policy interface (drawn from policy makers, policy adviser, practitioners, the private sector and academics) elicited a long list of emergent policy issues in which science and technology would feature strongly and which would also necessitate public engagement as policies are developed. This was then refined to a short list of top priorities for policy makers. Thirty issues were identified within broad areas of business and technology; energy and environment; government, politics and education; health, healthcare, population and aging; information, communication, infrastructure and transport; and public safety and national security

Evolution of pathogenicity and sexual reproduction in eight Candida genomes

Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes.publishe

Community development, regeneration and mental health

This chapter discusses community development, regeneration and mental health. It is part of a collection which bring together all of the key issues to offer an overview for students and practitioners alike

Density and current profiles numerically computed via stochastic simulations (blue and magenta dots, respectively) and analytically estimated (black lines) for and <i>L</i> = 1: (a, b) LD: = 0.2, = 1; (c, d) HD: = 1, = 0.2; (e, f) MC: = 1, = 1.

<p>Hopping and drop-off events are scheduled based on the Gillespie algorithm [<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005555#pcbi.1005555.ref041" target="_blank">41</a>]. All simulations, here and in the following, are for 10⁷ iteration steps (each iteration corresponds to one reaction: initiation, elongation, drop-off or termination). The first 2 ⋅ 10⁷ iterations were discarded to make sure that the system was in a steady state. Unless otherwise stated, a lattice size of 500 sites was used.</p

Density (a, c, e) and current (b, d, f) profiles for SLT2 (YHR030C), for <i>α</i> = 1<i>s</i>⁻¹, a in high density-like phase.

<p>Details, including the values of <i>γ</i>, are as in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1005555#pcbi.1005555.g014" target="_blank">Fig 14</a>. (a),(b): no ribosome drop-off <i>γ</i> = 0; (c), (d): physiological value of ribosome drop-off <i>γ</i> = 1.4 × 10⁻³ <i>s</i>⁻¹; (e), (f): ribosome drop-off under ethanol stress <i>γ</i> = 5.6 × 10⁻³ <i>s</i>⁻¹. The increasing slope in the 5’ to the 3’ direction characteristic of the HD phase is clearly visible in panel (c). Moreover, panel (d) illustrates the marked increase in the current at the 5’ end, compared to the case without ribosome drop-off (see panel (b)), also characteristic of the HD phase.</p

Both real branches <i>W</i>₀(<i>y</i>) (bold blue line) and <i>W</i>₋₁(<i>y</i>) (red line) of the Lambert function.

<p>The solid part of the blue line corresponds to the low density and maximal current phases, and the solid part of the red line corresponds to the high density phase.</p