"2A-like" signal sequences mediating translational recoding : a novel form of dual protein targeting

The authors gratefully acknowledge the support of the UK Biotechnology and Biological Sciences Research Council (BBSRC) who funded this research. The authors also gratefully acknowledge the support of the Wellcome Trust for the provision of mass spectrometry facilities at St Andrews.We report the initial characterisation of an N-terminal oligopeptide ‘2A-like’ sequence that is able to function both as a signal sequence and as a translational recoding element. Due to this translational recoding activity, two forms of nascent polypeptide are synthesised: (i) when 2A-mediated translational recoding has not occurred: the nascent polypeptide is fused to the 2A-like N-terminal signal sequence and the fusion translation product is targeted to the exocytic pathway, and, (ii) a translation product where 2A-mediated translational recoding has occurred: the 2A-like signal sequence is synthesised as a separate translation product and, therefore, the nascent (downstream) polypeptide lacks the 2A-like signal sequence and is localised to the cytoplasm. This type of dual-functional signal sequence results, therefore, in the partitioning of the translation products between the two sub-cellular sites and represents a newly described form of dual protein targeting.Publisher PDFPeer reviewe

Did Saturn's rings form during the Late Heavy Bombardment ?

The origin of Saturn\' s massive ring system is still unknown. Two popular scenarios - the tidal splitting of passing comets and the collisional destruction of a satellite - rely on a high cometary flux in the past. In the present paper we attempt to quantify the cometary flux during the Late Heavy Bombardment (LHB) to assess the likelihood of both scenarios. Our analysis relies on the so-called Nice model of the origin of the LHB (Tsiganis et al., 2005; Morbidelli et al., 2005; Gomes et al., 2005) and on the size distribution of the primordial trans-Neptunian planetesimals constrained in Charnoz & Morbidelli (2007). We find that the cometary flux on Saturn during the LHB was so high that both scenarios for the formation of Saturn rings are viable in principle. However, a more detailed study shows that the comet tidal disruption scenario implies that all four giant planets should have comparable ring systems whereas the destroyed satellite scenario would work only for Saturn, and perhaps Jupiter. This is because in Saturn\'s system, the synchronous orbit is interior to the Roche Limit, which is a necessary condition for maintaining a satellite in the Roche zone up to the time of the LHB. We also discuss the apparent elimination of silicates from the ring parent body implied by the purity of the ice in Saturn \' s rings. The LHB has also strong implications for the survival of the Saturnian satellites: all satellites smaller than Mimas would have been destroyed during the LHB, whereas Enceladus would have had from 40% to 70% chance of survival depending on the disruption model. In conclusion, these results suggest that the LHB is the sweet moment for the formation of a massive ring system around Saturn.Comment: 39 pages, 9 figures, 3 tables. Accepted for publication in ICARUS. New version with figures included in the tex

Anthony Blunt and Nicolas Poussin: A Queer Approach

The art historian Anthony Blunt (1907-1983), a homosexual and famously a Soviet spy, was a leading authority on the French painter Nicolas Poussin (1594-1665). In recent years, several scholars have noticed strange affinities between these two figures, affinities that relate to their ideas, to a common interest in secrecy and in covert knowledge, as well as to less definite attitudes that these scholars have had difficulty pinning down. This thesis proposes that these strange affinities may be explained by means of Queer Theory, which has afforded art historical scholarship a language and sets of concepts that allow the more difficult aspects of Blunt’s relationship to Poussin to be carefully anatomized. I argue that Blunt may have found in Poussin’s complex and ambiguous pictorial worlds both an inspiration for and a reflection of his multiple, contradictory identities and commitments. Meanwhile, I investigate what properties in Poussin’s art make possible this relationship, exploring how a kernel of homoerotic sensibility, entering Poussin’s oeuvre from the Arcadian pastoral tradition grows and diversifies to depict what I call queer bodies and to construct what I call queer spaces. Blunt’s art historical account of Poussin, the most influential account of the painter in the twentieth century, turns out to be but one facet of a deep and mutually-constitutive encounter between artist and art historian

Being framed by irony : AIDS and the art of General Idea

This thesis investigates transformations that took place within the work of the Toronto-based art collaborative General Idea before and after it came to deal with the AIDS crisis in the late 1980s and early 1990s and it explores how these relate to its ongoing concern with irony. In General Idea's work of the 70s, irony appears in many playful varieties. Yet the collaborative's irony seemed to wane as its work dealt increasingly with AIDS or, at least, its character seemed to change: it appeared to become more wry, critical, and less exuberant. In The AIDS Project (after 1987) and other, later works, General Idea's visual language becomes sparer and develops a public or installation-based inquiry into ambiguities around originality and cultural transmission and dissemination that parallels the behaviour of the AIDS virus itself or aspects of its cultural contexts. But this thesis argues that these later series represent a continuation of many of the collaborative's earlier concerns and not at all their abandonment. Drawing upon close analysis of works throughout General Idea's oeuvre , as well a theoretical investigation of irony, "Being Framed by Irony: AIDS and the Art of General Idea" seeks to anatomize and explain these developments

Being framed by irony : AIDS and the art of General Idea

This thesis investigates transformations that took place within the work of the Toronto-based art collaborative General Idea before and after it came to deal with the AIDS crisis in the late 1980s and early 1990s and it explores how these relate to its ongoing concern with irony. In General Idea's work of the 70s, irony appears in many playful varieties. Yet the collaborative's irony seemed to wane as its work dealt increasingly with AIDS or, at least, its character seemed to change: it appeared to become more wry, critical, and less exuberant. In The AIDS Project (after 1987) and other, later works, General Idea's visual language becomes sparer and develops a public or installation-based inquiry into ambiguities around originality and cultural transmission and dissemination that parallels the behaviour of the AIDS virus itself or aspects of its cultural contexts. But this thesis argues that these later series represent a continuation of many of the collaborative's earlier concerns and not at all their abandonment. Drawing upon close analysis of works throughout General Idea's oeuvre , as well a theoretical investigation of irony, "Being Framed by Irony: AIDS and the Art of General Idea" seeks to anatomize and explain these developments

Nurse Retention Strategies in the Healthcare Industry

Nurse turnover in the healthcare industry is detrimental to the quality-of-care patients receive, organizational financial health, and nurse job satisfaction. Nurse managers who lack effective nurse retention strategies might struggle to reduce voluntary turnover, which can adversely impact nurse job satisfaction and patient care quality. Guided by the unfolding model of voluntary employee turnover and job embeddedness theory, the purpose of this qualitative multiple case study was to explore retention strategies nurse managers use to reduce the voluntary turnover of nurses. The participants were three nurse managers at three hospitals in central and southern Illinois with proven strategies to reduce nurse turnover. Data collection included semistructured video conferencing interviews with participants and analysis of publicly available company documents and analyzed using Yin’s five qualitative data analysis stages. Three key themes emerged: employee-organization relationships and communications; benefits, rewards, and recognition; and employee engagement and participation. The key recommendation is for nurse managers to foster employee-organization relationships by implementing strategies to drive timely and effective communication. Implications for positive social change include the potential to improve quality-of-care for patients, increase organizational stability, promote nurse job satisfaction, and potentially reduce healthcare, which could benefit community members

Going global: Arabian palaeoclimate and human evolution

The vast Arabian deserts sit at a crucial interface between Europe and sub-Saharan Africa and acts as a geographical barrier between Afrotropical and Eurasian fauna. However, punctuated increases of rainfall throughout the Pleistocene created “green” deserts that are increasingly related to mammalian dispersals. These “windows of opportunity” were crucial for occupation and dispersal of hominin species and acted as important steppingstones on the way to the global colonisation of Homo sapiens. Despite a growing body of palaeoclimate information from marine sediment cores and relict palaeolake deposits, there remain significant gaps in important palaeoclimatological questions. For example, what was the precise timing, duration and frequency of wet events? What precipitation regime delivered precipitation across Arabia? How did precipitation vary within and between pluvial periods? What sorts of environments flourished with increased precipitation? Not only are these pertinent questions for accurately characterising past climates and environments but answering these can identify favourable hominin dispersal windows throughout the Pleistocene. To elucidate these issues, this thesis aimed to generate new speleothem-based palaeoclimate records from Mukalla (Yemen), Hoti (Oman), Broken-Leg, Star and Surprise (Saudi Arabia) Caves. South Arabian Humid Periods (SAHPs) were identified by U-Pb and 230Th age determinations of stalagmite growth from Mukalla and Hoti Cave. These SAHPs were a result of African and Indian Summer Monsoon incursions during insolation maxima within peak interglacial periods and warm substages up to 1.1 million years ago, as identified by fluid inclusion water δD and δ18O and calcite δ18O measurements. This increased annual precipitation to >300 mm yr-1 and allowed C4 vegetation to flourish, as determined by calcite δ13C measurements. Identification of sub-annual cycles of δ13C and δ18O indicates environments were highly seasonal, characterised by a “wetter” summer and “drier” winter. Additional U-Pb and 230Th dating of stalagmites from Broken-Leg, Star and Surprise Cave reflect these findings, indicating that wet periods occurred during warm periods of the Pliocene and Early-Pleistocene, Together, this information shows that Saharo-Arabian palaeoenvironmental fluctuation – governed by monsoon variability – provided frequent opportunities for hominin occupation of Arabia and dispersal throughout the Plio-Pleistocene

NMR-based metabolic characterization of chicken tissues and biofluids: a model for avian research

Introduction Poultry is one of the most consumed meat in the world and its related industry is always looking for ways to improve animal welfare and productivity. It is therefore essential to understand the metabolic response of the chicken to new feed formulas, various supplements, infections and treatments. Objectives As a basis for future research investigating the impact of diet and infections on chicken’s metabolism, we established a high-resolution proton nuclear magnetic resonance (NMR)-based metabolic atlas of the healthy chicken (Gallus gallus). Methods Metabolic extractions were performed prior to 1H-NMR and 2D NMR spectra acquisition on twelve biological matrices: liver, kidney, spleen, plasma, egg yolk and white, colon, caecum, faecal water, ileum, pectoral muscle and brain of 6 chickens. Metabolic profiles were then exhaustively characterized. Results Nearly 80 metabolites were identified. A cross-comparison of these matrices was performed to determine metabolic variations between and within each section and highlighted that only eight core metabolites were systematically found in every matrice. Conclusion This work constitutes a database for future NMR-based metabolomic investigations in relation to avian production and health

Identifying lower limb specific and generalised joint hypermobility in adults: validation of the Lower Limb Assessment Score

Background The Lower Limb Assessment Score (LLAS) has only been validated in a paediatric population. The aim of this study was to validate the use of the LLAS in an adult population by: i) evaluating its ability to discriminate between different extents of lower limb hypermobility, ii) establishing a cut-off score to identify lower limb hypermobility, and iii) determining if the LLAS is able to identify Generalised Joint Hypermobility (GJH). Methods Participants were recruited across three groups representing varying degrees of hypermobility. They were assessed using the LLAS, Beighton score and clinical opinion. Pearson’s correlation coefficient and MANOVA were used to assess between-group differences in the LLAS. The cut-off score was determined using median and inter-quartile ranges and the Receiver Operator Characteristic Curve. The ability of the LLAS to identify GJH was assessed using percent agreement with clinical opinion. Results One hundred twelve participants aged 18–40 years were recruited. The LLAS distinguished the control from the likely hypermobile and known hypermobile cohorts (both p \u3c 0.001), as well as the likely hypermobile from the known hypermobile cohort (p = 0.003). The LLAS cut-off score for identifying lower limb hypermobility was ≥7/12 with a specificity of 86% and sensitivity of 68%. The LLAS accurately identified those with GJH with high percentage agreement compared to clinical opinion across all cohorts (69–98%). Conclusions The LLAS is a valid tool for identifying lower limb specific hypermobility and GJH in adults at a cut-off score of ≥7/12. It demonstrates excellent specificity and moderate sensitivity, and discriminates well between extents of hypermobility