2,326 research outputs found

    The eIF4F and eIFiso4F Complexes of Plants: An Evolutionary Perspective

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    Translation initiation in eukaryotes requires a number of initiation factors to recruit the assembled ribosome to mRNA. The eIF4F complex plays a key role in initiation and is a common target point for regulation of protein synthesis. Most work on the translation machinery of plants to date has focused on flowering plants, which have both the eIF4F complex (eIF4E and eIF4G) as well as the plant-specific eIFiso4F complex (eIFiso4E and eIFiso4G). The increasing availability of plant genome sequence data has made it possible to trace the evolutionary history of these two complexes in plants, leading to several interesting discoveries. eIFiso4G is conserved throughout plants, while eIFiso4E only appears with the evolution of flowering plants. The eIF4G N-terminus, which has been difficult to annotate, appears to be well conserved throughout the plant lineage and contains two motifs of unknown function. Comparison of eIFiso4G and eIF4G sequence data suggests conserved features unique to eIFiso4G and eIF4G proteins. These findings have answered some questions about the evolutionary history of the two eIF4F complexes of plants, while raising new ones

    Community pharmacists’ views of using a screening tool to structure medicines use reviews for older people: Findings from qualitative interviews

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    Background The Medicines use review (MUR) service, provided by community pharmacists, seeks to optimise patients’ use of medicines. There is limited evidence on the clinical effectiveness of this service. Structuring MURs to include an assessment of prescribing appropriateness, facilitated by a validated prescribing screening tool, has the capacity to enhance this service. Objective To explore community pharmacists’ views on the facilitators and barriers towards the utilisation of a screening tool as a guide to conducting structured MURs. Setting Community Pharmacy, Northern Ireland. Method Using the 14 domain Theoretical Domains Framework (TDF), semi-structured interviews were conducted with community pharmacists. Interviews were digitally recorded, transcribed verbatim and analysed using the Framework method. Main Outcome Measure Pharmacists’ views towards utilisation of a screening tool as a guide to conducting structured MURs. Results Based on the analysis of 15 interviews, 11 TDF domains (‘Knowledge’, ‘Skills’, ‘Social and professional role and identity’, ‘Beliefs about capabilities’, ‘Beliefs about consequences’, ‘Reinforcement’, ‘Goals’, ‘Memory, attention and decision process’, ‘Environmental context and resources’, ‘Social influences’, ‘Behavioural regulation’) were deemed relevant. Facilitators included: knowledge of patients, clinical knowledge, perceived professional role, patients’ clinical outcomes, influence of peers. Barriers included: prioritisation of other clinical activities, inability to access patients’ clinical information, perceived alienation from the primary healthcare team and staffing issues. Conclusions Using the TDF, key facilitators and barriers were identified in the use of a screening tool as a guide to conducting MURs. These findings may assist in further development of MURs as a means to optimise patients’ medicines use

    Ubiquitination and proteasomal degradation of ATG12 regulates its proapoptotic activity

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    During macroautophagy, conjugation of ATG12 to ATG5 is essential for LC3 lipidation and autophagosome formation. Additionally, ATG12 has ATG5-independent functions in diverse processes including mitochondrial fusion and mitochondrial-dependent apoptosis. In this study, we investigated the regulation of free ATG12. In stark contrast to the stable ATG12–ATG5 conjugate, we find that free ATG12 is highly unstable and rapidly degraded in a proteasome-dependent manner. Surprisingly, ATG12, itself a ubiquitin-like protein, is directly ubiquitinated and this promotes its proteasomal degradation. As a functional consequence of its turnover, accumulation of free ATG12 contributes to proteasome inhibitor-mediated apoptosis, a finding that may be clinically important given the use of proteasome inhibitors as anticancer agents. Collectively, our results reveal a novel interconnection between autophagy, proteasome activity, and cell death mediated by the ubiquitin-like properties of ATG12

    The impact of ozone depleting substances on the circulation, temperature, and salinity of the Southern Ocean: An attribution study with CESM1(WACCM)

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    Observations show robust changes in the circulation, temperature, and salinity of the Southern Ocean in recent decades. To what extent these changes are related to the formation of the ozone hole in the late twentieth century is an open question. Using a comprehensive chemistry-climate Earth system model, we contrast model runs with varying and with fixed surface concentrations of ozone depleting substances (ODS) from 1955 to 2005. In our model, ODS cause the majority of the summertime changes in surface wind stress which, in turn, induce a clear poleward shift of the ocean's meridional overturning circulation. In addition, more than 30% of the model changes in the temperature and salinity of the Southern Ocean are caused by ODS. These findings offer unambiguous evidence that increased concentrations of ODS in the late twentieth century are likely to have been been an important driver of changes in the Southern Ocean

    Short GRB 130603B: Discovery of a jet break in the optical and radio afterglows, and a mysterious late-time X-ray excess

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    We present radio, optical/NIR, and X-ray observations of the afterglow of the short-duration 130603B, and uncover a break in the radio and optical bands at 0.5 d after the burst, best explained as a jet break with an inferred jet opening angle of 4-8 deg. GRB 130603B is only the third short GRB with a radio afterglow detection to date, and the first time that a jet break is evident in the radio band. We model the temporal evolution of the spectral energy distribution to determine the burst explosion properties and find an isotropic-equivalent kinetic energy of (0.6-1.7) x 10^51 erg and a circumburst density of 5 x 10^-3-30 cm^-3. From the inferred opening angle of GRB 130603B, we calculate beaming-corrected energies of Egamma (0.5-2) x 10^49 erg and EK (0.1-1.6) x 10^49 erg. Along with previous measurements and lower limits we find a median short GRB opening angle of 10 deg. Using the all-sky observed rate of 10 Gpc^-3 yr^-1, this implies a true short GRB rate of 20 yr^-1 within 200 Mpc, the Advanced LIGO/VIRGO sensitivity range for neutron star binary mergers. Finally, we uncover evidence for significant excess emission in the X-ray afterglow of GRB 130603B at >1 d and conclude that the additional energy component could be due to fall-back accretion or spin-down energy from a magnetar formed following the merger.Comment: Submitted to ApJ; emulateapj style; 10 pages, 1 table, 3 figure

    Spatial and temporal variability in costs and effectiveness in phosphorus loss mitigation at farm scale: A scenario analysis

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    Current policy instruments under the EU Water Framework Directive (WFD) to mitigate phosphorus (P) loss require that P use on farms is managed through regulation of farm gate P balances. Regulation at farm scale does not account for spatial variability in nutrient use and soil fertility at field scale, affecting the costs and effectiveness of farm gate measures. This study simulated the implementation of a P loss mitigation measure coupled with improving soil fertility so that farm productivity would not be compromised. The measure was simulated at field scale and the costs and effectiveness assessed at farm scale. Effectiveness was expressed as the time taken for excessive soil P levels to decline to levels that matched off-takes and this varied temporally and spatially within and between farms ranging from 1 to 8 years. Sub-optimum soil fertility was corrected on all fields across both farms, with applications of other soil nutrients and lime to protect productivity. An increase in costs ranging from 1.5 to 116% was predicted in the first two years of the measure on both farms after-which savings of 15-31% were predicted for each subsequent year until the measure was effective in year 9. Despite initial cost increase, there was no statistically significant difference in costs over the time taken for the measure to be effective, when compared to baseline costs. Successful implementation of measures should consider the impact on farm costs and time taken for measures to environmentally effective. Adoption of measures could improve if demonstrating to farmers that costs will not vary significantly from current practice and in time may results in savings if measures are paired with correcting soil fertility and increasing yields. This 'win-win' approach could be used into the future to ensure successful implementation and uptake of measures within the farming community

    Pathways for nutrient loss to water with emphasis on phosphorus

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    Teagasc wishes to acknowledge the support of the Environmental Research Technological Development and Innovation (ERTDI) Programme under the Productive Sector Operational Programme which was financed by the Irish Government under the National Development Plan 2000-2006.End of project reportThe main objective of this project was to study phosphorus (P) loss from agricultural land under a range of conditions in Ireland, to quantify the main factors influencing losses and make recommendations on ways to reduce these losses. This report is a synthesis of the main conclusions and recommendations from the results of the studies. The final reports from the individual sub-projects in this project are available from the EPA (www.epa.ie).Environmental Protection Agenc
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