Dynamic oscillation of translation and stress granule formation mark the cellular response to virus infection

Virus infection-induced global protein synthesis suppression is linked to assembly of stress granules (SGs), cytosolic aggregates of stalled translation preinitiation complexes. To study long-term stress responses, we developed an imaging approach for extended observation and analysis of SG dynamics during persistent hepatitis C virus (HCV) infection. In combination with type 1 interferon, HCV infection induces highly dynamic assembly/disassembly of cytoplasmic SGs, concomitant with phases of active and stalled translation, delayed cell division, and prolonged cell survival. Double-stranded RNA (dsRNA), independent of viral replication, is sufficient to trigger these oscillations. Translation initiation factor eIF2a phosphorylation by protein kinase R mediates SG formation and translation arrest. This is antagonized by the upregulation of GADD34, the regulatory subunit of protein phosphatase 1 dephosphorylating eIF2a. Stress response oscillation is a general mechanism to prevent long-lasting translation repression and a conserved host cell reaction to multiple RNA viruses, which HCV may exploit to establish persistence.

Stomatal proxy record of CO2 concentrations from the last termination suggests an important role for CO2 at climate change transitions

A new stomatal proxy-based record of CO₂ concentrations ([CO₂]), based on Betula nana (dwarf birch) leaves from the Hässeldala Port sedimentary sequence in south-eastern Sweden, is presented. The record is of high chronological resolution and spans most of Greenland Interstadial 1 (GI-1a to 1c, Allerød pollen zone), Greenland Stadial 1 (GS-1, Younger Dryas pollen zone) and the very beginning of the Holocene (Preboreal pollen zone). The record clearly demonstrates that i) [CO₂] were significantly higher than usually reported for the Last Termination and ii) the overall pattern of CO₂ evolution through the studied time period is fairly dynamic, with significant abrupt fluctuations in [CO₂] when the climate moved from interstadial to stadial state and vice versa. A new loss-on-ignition chemical record (used here as a proxy for temperature) lends independent support to the Hässeldala Port [CO₂] record. The large-amplitude fluctuations around the climate change transitions may indicate unstable climates and that " tipping-point" situations were involved in Last Termination climate evolution. The scenario presented here is in contrast to [CO₂] records reconstructed from air bubbles trapped in ice, which indicate lower concentrations and a gradual, linear increase of [CO₂] through time. The prevalent explanation for the main climate forcer during the Last Termination being ocean circulation patterns needs to re-examined, and a larger role for atmospheric [CO₂] considered.

Lost in translation: Public policies, evidence-based practice, and Autism Spectrum Disorder

Prevalence rates of autism spectrum disorder have risen dramatically over the past few decades (now estimated at 1:50 children). The estimated total annual cost to the public purse in the United States is US$137 billion, with an individual lifetime cost in the United Kingdom estimated at between £0.8 million and £1.23 million depending on the level of functioning. The United Nations Convention for the Rights of Persons with Disabilities has enshrined full and equal human rights—for example, for inclusion, education and employment—and there is ample evidence that much can be achieved through adequate support and early intensive behavioural interventions. Not surprisingly, most governments worldwide have devised laws, policies, and strategies to improve services related to autism spectrum disorder, yet intriguingly the approaches differ considerably across the globe. Using Northern Ireland as a case in point, we look at relevant governmental documents and offer international comparisons that illustrate inconsistencies akin to a “postcode lottery” of services.

The Map Defines the Territory: Remodelling NGO Partnerships for Knowledge Translation in Transition Contexts

The initial impetus for a theoretical exploration of organisational relationships is based on case study research on a Bulgarian NGO's implementation of values and goals into practices under a guiding relationship from a very experienced UK organisation in the same field. Findings diverged from conventional accounts of developing NGOs' dependence on more developed counterparts and that case study findings characterised the inter- dependency between the two organisations as more alike to a collaborative knowledge ...

Agency Termination in Ireland: Culls and bonfires, or life after death?

The termination of state agencies has been a prominent aspect of administrative 'rationalization' programmes arising from the Global Financial Crisis. In this article, the frequency and type of agency terminations that have occurred in Ireland post-2008 are examined in longitudinal perspective. Following a consideration of agency types, the logic of agency rationalization is explored with a focus on the different ways in which agencies are terminated. Drawing on a unique dataset of Irish state agencies over a 90-year period, the article presents evidence concerning the degree to which terminations over the 2008-11 period differ, if at all, from those that have occurred previously. In concluding, the article proposes that rather than witnessing agency 'culls' and 'bonfires', there is 'life after death' for agencies and their work.

The latest LGM culmination of the Garda Glacier (Italian Alps) and the onset of glacial termination. Age of glacial collapse and vegetation chronosequence

In the deglacial sequence of the largest end moraine system of the Italian Alps, we focused on the latest culmination of the Last Glacial Maximum, before a sudden downwasting of the piedmontane lobe occupying the modern lake basin. We obtained a robust chronology for this culmination and for the subsequent deglacial history by cross-radiocarbon dating of a proximal fluvioglacial plain and of a deglacial continuous lake sedimentation. We used reworked dinocysts to locate sources of glacial abrasion and to mark the input of glacial meltwater until depletion. The palynological record from postglacial lake sediments provided the first vegetation chronosequence directly reacting to the early Lateglacial withdrawal so far documented in the Alps.

Glacier collapse occurred soon after 17.46 +/- 0.2 ka cal BP, which is, the Manerba advance culmination. Basin deglaciation of several overdeepened foreland piedmont lakes on southern and northern sides of the Alps appears to be synchronous at millennial scale and near-synchronous with large-scale glacial retreat at global scale. The pioneering succession shows a first afforestation step at a median modeled age of 64 years after deglaciation, while rapid tree growth lagged 7 centuries. Between 16.4 +/- 0.16 and 15.5 +/- 0.16 ka cal BP, a regressive phase interrupted forest growth marking a Lateglacial phase of continental-dry climate predating GI-1. This event, spanning the most advanced phases of North-Atlantic H1, is consistently radiocarbon-framed at three deglacial lake records so far investigated on the Italian side of the Alps. Relationships with the Gschnitz stadial from the Alpine record of Lateglacial advances are discussed

Successful translation of Academic Research into wider Economic Impact: University of Southampton, Distinguished Lecture

No abstract available

The influence of high air entry filter on the testing of unsaturated soils using the axis translation technique

Suction is an important stress variable that is required for reliable predictions of the likely performance of unsaturated soils. The axis translation technique is the best established method of measuring or controlling suction; however, the success of this application is heavily dependent on the rating of the high air entry filter (HAF) and how it is incorporated into the testing system. This paper reports some basic experiments in which samples of unsaturated kaolin were brought to saturation in stages using 5 bar and 15 bar HAFs. The results have shown that the water equilibrium in unsaturated soils is greatly affected by the rating of filters. The findings also suggest that the flow through unsaturated soils is not necessarily governed by the one-dimensional consolidation theory that was developed for saturated soils, and this may be attributed to the bimodal pore size distribution of unsaturated soils.

Laboratizing the border: The production, translation and anticipation of security technologies

This paper critically interrogates how borders are produced by scientists, engineers and security experts in advance of the actual deployment of technical devices they develop. This paper explores the prior stages of translation and decision-making as a socio-technical device is conceived and developed. Drawing on in-depth interviews, observations and ethnographic research of the EU-funded Handhold project (consisting of nine teams in five countries), it explores how assumptions about the way security technologies will and should perform at the border shape the way that scientists, engineers, and security experts develop a portable, integrated device to detect CBRNE threats at borders. In disaggregating the moments of sovereign decision making across multiple sites and times, this paper questions the supposed linearity of how science comes out of and feeds back into the world of border security. An interrogation of competing assumptions and understandings of security threats and needs, of competing logics of innovation and pragmatism, of the demands of differentiated temporalities in detection and interrogation, and of the presumed capacities, behaviours, and needs of phantasmic competitors and end-users reveals a complex, circulating and co-constitutive process of device development that laboratises the border itself. We trace how sovereign decisions are enacted as assemblages in the antecedent register of device development itself through the everyday decisions of researchers in the laboratory, and the material components of the Handhold device itself.

Knowledge translation in men’s health research: development and delivery of content for use online

Background: Men can be hard to reach with face-to-face health-related information, while increasingly, research shows that they are seeking health information from online sources. Recognizing this trend, there is merit in developing innovative online knowledge translation (KT) strategies capable of translating research on men’s health into engaging health promotion materials. While the concept of KT has become a new mantra for researchers wishing to bridge the gap between research evidence and improved health outcomes, little is written about the process, necessary skills, and best practices by which researchers can develop online knowledge translation.
Objective: Our aim was to illustrate some of the processes and challenges involved in, and potential value of, developing research knowledge online to promote men’s health.

Methods: We present experiences of KT across two case studies of men’s health. First, we describe a study that uses interactive Web apps to translate knowledge relating to Canadian men’s depression. Through a range of mechanisms, study findings were repackaged with the explicit aim of raising awareness and reducing the stigma associated with men’s depression and/or help-seeking. Second, we describe an educational resource for teenage men about unintended pregnancy, developed for delivery in the formal Relationship and Sexuality Education school curricula of Ireland, Northern Ireland (United Kingdom), and South Australia. The intervention is based around a Web-based interactive film drama entitled “If I Were Jack”.

Results: For each case study, we describe the KT process and strategies that aided development of credible and well-received online content focused on men’s health promotion. In both case studies, the original research generated the inspiration for the interactive online content and the core development strategy was working with a multidisciplinary team to develop this material through arts-based approaches. In both cases also, there is an acknowledgment of the need for gender and culturally sensitive information. Both aimed to engage men by disrupting stereotypes about men, while simultaneously addressing men through authentic voices and faces. Finally, in both case studies we draw attention to the need to think beyond placement of content online to delivery to target audiences from the outset.

Conclusions: The case studies highlight some of the new skills required by academics in the emerging paradigm of translational research and contribute to the nascent literature on KT. Our approach to online KT was to go beyond dissemination and diffusion to actively repackage research knowledge through arts-based approaches (videos and film scripts) as health promotion tools, with optimal appeal, to target male audiences. Our findings highlight the importance of developing a multidisciplinary team to inform the design of content, the importance of adaptation to context, both in terms of the national implementation context and consideration of gender-specific needs, and an integrated implementation and evaluation framework in all KT work.

Ab initio diffusional potential energy surface for CO chemisorption on Pd{110} at high coverage:Coupled translation and rotation

The ground state potential energy surface for CO chemisorption across Pd{110} has been calculated using density functional theory with gradient corrections at monolayer coverage. The most stable site corresponds well with the experimental adsorption heat, and it is found that the strength of binding to sites is in the following order: pseudo-short-bridge>atop>long-bridge>hollow. Pathways and transition states for CO surface diffusion, involving a correlation between translation and orientation, are proposed and discussed. (C) 1997 American Institute of Physics.