Functional analysis of Arabidopsis DOA10-like E3 ligases

The ubiquitin proteasome system (UPS) performs the bulk of targeted protein degradation within eukaryotic cells. As such it is crucial for regulating protein abundance, destroying harmful misfolded proteins and for facilitating responses to stimuli. UPS substrates are identified by E3 ligase enzymes, which catalyse their ubiquitination through recognition of degrons (sequences of amino acids encoding degradation signals). ScDoa10 is an E3 ligase of the yeast endoplasmic reticulum-associated degradation (ERAD) system that has been reported to recognise acetylated N-termini as degrons, as part of the Ac/N-degron pathway. It is shown here that one Arabidopsis thaliana homolog of ScDoa10 (AtDOA10A) can functionally complement the yeast E3 both in the response to hygromycin and in the degradation of a substrate (AtSQE1), demonstrating conservation of function. A second homolog, AtDOA10B, which is specific to Brassicaceae, was unable to complement ScDoa10 despite sequence and structural similarities. Despite evidence of functional conservation for AtDOA10A, multiomic analyses, including transcriptomics, quantitative proteomics and N-terminal (Nt-)acetylomics, of seedlings with reduced levels of AtDOA10s revealed no evidence of an accumulation of Nt-acetylated substrates, suggesting that an AtDOA10-mediated Ac/N-degron pathway is not a significant contributor to global protein degradation in Arabidopsis. Similarly, targeting of AtSQE1, the first identified likely substrate of AtDOA10A, was also independent of its Nt-acetylation status, although, interestingly, disruption of Nt-acetylation machinery did indirectly affect AtSQE1’s stability. This supports other recent investigations which suggest that Nt-acetylation does not act as a universal degradation signal but also highlights the significant indirect impacts of this post-translational modification on proteostasis

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Chromosome‑level genome sequence of the Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) highlights regions of introgression with O. mossambicus

Background The Nile tilapia (Oreochromis niloticus) is the third most important freshwater fish for aquaculture. Its success is directly linked to continuous breeding efforts focusing on production traits such as growth rate and weight. Among those elite strains, the Genetically Improved Farmed Tilapia (GIFT) programme initiated by WorldFish is now distributed worldwide. To accelerate the development of the GIFT strain through genomic selection, a high-quality reference genome is necessary. Results Using a combination of short (10X Genomics) and long read (PacBio HiFi, PacBio CLR) sequencing and a genetic map for the GIFT strain, we generated a chromosome level genome assembly for the GIFT. Using genomes of two closely related species (O. mossambicus, O. aureus), we characterised the extent of introgression between these species and O. niloticus that has occurred during the breeding process. Over 11 Mb of O. mossambicus genomic material could be identified within the GIFT genome, including genes associated with immunity but also with traits of interest such as growth rate. Conclusion Because of the breeding history of elite strains, current reference genomes might not be the most suitable to support further studies into the GIFT strain. We generated a chromosome level assembly of the GIFT strain, characterising its mixed origins, and the potential contributions of introgressed regions to selected traits

Stakeholders’ perspectives on clinical trial acceptability and approach to consent within a limited timeframe: a mixed methods study

Objectives The Bronchiolitis Endotracheal Surfactant Study (BESS) is a randomised controlled trial to determine the efficacy of endo-tracheal surfactant therapy for critically ill infants with bronchiolitis. To explore acceptability of BESS, including approach to consent within a limited time frame, we explored parent and staff experiences of trial involvement in the first two bronchiolitis seasons to inform subsequent trial conduct.Design A mixed-method embedded study involving a site staff survey, questionnaires and interviews with parents approached about BESS.Setting Fourteen UK paediatric intensive care units.Participants Of the 179 parents of children approached to take part in BESS, 75 parents (of 69 children) took part in the embedded study. Of these, 55/69 (78%) completed a questionnaire, and 15/69 (21%) were interviewed. Thirty-eight staff completed a questionnaire.Results Parents and staff found the trial acceptable. All constructs of the Adapted Theoretical Framework of Acceptability were met. Parents viewed surfactant as being low risk and hoped their child’s participation would help others in the future. Although parents supported research without prior consent in studies of time critical interventions, they believed there was sufficient time to consider this trial. Parents recommended that prospective informed consent should continue to be sought for BESS. Many felt that the time between the consent process and intervention being administered took too long and should be ‘streamlined’ to avoid delays in administration of trial interventions. Staff described how the training and trial processes worked well, yet patients were missed due to lack of staff to deliver the intervention, particularly at weekends.Conclusion Parents and staff supported BESS trial and highlighted aspects of the protocol, which should be refined, including a streamlined informed consent process. Findings will be useful to inform proportionate approaches to consent in future paediatric trials where there is a short timeframe for consent discussions.Trial registration number ISRCTN11746266