The Ideal Pension System for Belgium

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Structural basis for the substrate specificity and catalytic features of pseudouridine kinase from Arabidopsis thaliana

RNA modifications can regulate the stability of RNAs, mRNA-protein interactions, and translation efficiency. Pseudouridine is a prevalent RNA modification, and its metabolic fate after RNA turnover was recently characterized in eukaryotes, in the plant Arabidopsis thaliana. Here, we present structural and biochemical analyses of PSEUDOURIDINE KINASE from Arabidopsis (AtPUKI), the enzyme catalyzing the first step in pseudouridine degradation. AtPUKI, a member of the PfkB family of carbohydrate kinases, is a homodimeric α/β protein with a protruding small β-strand domain, which serves simultaneously as dimerization interface and dynamic substrate specificity determinant. AtPUKI has a unique nucleoside binding site specifying the binding of pseudourine, in particular at the nucleobase, by multiple hydrophilic interactions, of which one is mediated by a loop from the small β-strand domain of the adjacent monomer. Conformational transition of the dimerized small β-strand domains containing active site residues is required for substrate specificity. These dynamic features explain the higher catalytic efficiency for pseudouridine over uridine. Both substrates bind well (similar Km), but only pseudouridine is turned over efficiently. Our studies provide an example for structural and functional divergence in the PfkB family and highlight how AtPUKI avoids futile uridine phosphorylation which in vivo would disturb pyrimidine homeostasis. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research

Testing normative and self-appraisal feedback in an online slot-machine pop-up in a real-world setting

Over the last few years, there have been an increasing number of gaming operators that have incorporated on-screen pop-up messages while gamblers play on slot machines and/or online as one of a range of tools to help encourage responsible gambling. Coupled with this, there has also been an increase in empirical research into whether such pop-up messages are effective, particularly in laboratory settings. However, very few studies have been conducted on the utility of pop-up messages in real-world gambling settings. The present study investigated the effects of normative and self-appraisal feedback in a slot machine pop-up message compared to a simple (non-enhanced) pop-up message. The study was conducted in a real-world gambling environment by comparing the behavioral tracking data of two representative random samples of 800,000 gambling sessions (i.e., 1.6 million sessions in total) across two conditions (i.e., simple pop-up message versus an enhanced pop-up message). The results indicated that the additional normative and self-appraisal content doubled the number of gamblers who stopped playing after they received the enhanced pop-up message (1.39%) compared to the simple pop-up message (0.67%). The data suggest that pop-up messages influence only a small number of gamblers to cease long playing sessions and that enhanced messages are slightly more effective in helping gamblers to stop playing in-session

Une méta-analyse des appels à la peur : implications pour des campagnes de santé publique efficaces

La littérature sur l’appel à la peur est ici analysée et synthétisée à l’aide d’une méta-analyse. Cette dernière suggère que les appels à la peur de forte intensité produisent des perceptions élevées de sévérité de la menace et de vulnérabilité et qu’ils ont un impact persuasif plus important que les appels à la peur de faible intensité. Les résultats indiquent également que les appels à la peur motivent la mise en place d’actions adaptées au contrôle du danger, comme l’acceptation du message, et la mise en place d’actions de contrôle de la peur mal adaptées, comme l’évitement défensif ou la réactance. Il apparaît que des messages générant une forte peur et ayant une efficacité élevée favorisent plus le changement de comportement, alors que les messages générant une forte peur, mais une efficacité faible, favorisent l’apparition de réactions défensives. Des perspectives de recherches ainsi que des implications pratiques sont envisagées.The fear appeal literature is examined in a comprehensive synthesis using metaanalytical techniques. The meta-analysis suggests that strong fear appeals produce high levels of perceived severity and susceptibility, and are more persuasive than low or weak fear appeals. The results also indicate that fear appeal motivate adaptive danger control actions such as message acceptance and maladaptive fear control actions such as defensive avoidance or reactance. It appears that strong fear appeals and high-efficacy messages produce the greatest behavior change, whereas strong fear appeals with low-efficacy messages produce the greatest levels of defensive responses. Future directions and practical implications are provided

The role of the cerebellum in social and non-social action sequences : a preliminary LF-rTMS study

An increasing number of studies demonstrated the involvement of the cerebellum in (social) sequence processing. The current preliminary study is the first to investigate the causal involvement of the cerebellum in sequence generation, using low-frequency repetitive transcranial magnetic stimulation (LF-rTMS). By targeting the posterior cerebellum, we hypothesized that the induced neuro-excitability modulation would lead to altered performance on a Picture and Story sequencing task, which involve the generation of the correct chronological order of various social and non-social stories depicted in cartoons or sentences. Our results indicate that participants receiving LF-rTMS over the cerebellum, as compared to sham participants, showed a stronger learning effect from pre to post stimulation for both tasks and for all types of sequences (i.e. mechanical, social scripts, false belief, true belief). No differences between sequence types were observed. Our results suggest a positive effect of LF-rTMS on sequence generation. We conclude that the cerebellum is causally involved in the generation of sequences of social and nonsocial events. Our discussion focuses on recommendations for future studies

Challenges for Preventive Digital Stress Management Systems - Identifying Requirements by Conducting Qualitative Interviews

Personal health depends on physical factors as well as on the subject’s behavior and lifestyle. Stress is the cause of numerous diseases unless it is in balance with sufficient relaxation and rest. Nowadays, continuous stress and, as a consequence, a burnout are steadily increasing, thus the need for prevention and stress management is growing too. Digital technologies allow for new methods of stress management to prevent burnout. However, the requirements for such systems remain largely unexplored. This work closes this research gap by offering a qualitative requirement survey and its analysis. For this purpose, 15 semi-structured interviews were conducted from four different perspectives (health insurance companies, care providers, private sector and users), which allowed to derive the requirements for successful digital stress management systems. These can be divided into three categories: Human Centricity, Medicine and Technology

Aspects of the Mass Distribution of Interstellar Dust Grains in the Solar System from In-Situ Measurements

The in-situ detection of interstellar dust grains in the Solar System by the dust instruments on-board the Ulysses and Galileo spacecraft as well as the recent measurements of hyperbolic radar meteors give information on the properties of the interstellar solid particle population in the solar vicinity. Especially the distribution of grain masses is indicative of growth and destruction mechanisms that govern the grain evolution in the interstellar medium. The mass of an impacting dust grain is derived from its impact velocity and the amount of plasma generated by the impact. Because the initial velocity and the dynamics of interstellar particles in the Solar System are well known, we use an approximated theoretical instead of the measured impact velocity to derive the mass of interstellar grains from the Ulysses and Galileo in-situ data. The revised mass distributions are steeper and thus contain less large grains than the ones that use measured impact velocities, but large grains still contribute significantly to the overall mass of the detected grains. The flux of interstellar grains with masses $> 10^{-14} {\rm kg}$ is determined to be $1\cdot 10^{-6} {\rm m}^{-2} {\rm s}^{-1}$. The comparison of radar data with the extrapolation of the Ulysses and Galileo mass distribution indicates that the very large ($m > 10^{-10} {\rm kg}$) hyperbolic meteoroids detected by the radar are not kinematically related to the interstellar dust population detected by the spacecraft.Comment: 14 pages, 11 figures, to appear in JG

Multi-site, multi-year monitoring of the oscillating Algol-type eclipsing binary CT Her

We present the results of a multi-site photometric campaign carried out in 2004-2008 for the Algol-type eclipsing binary system CT Her, the primary component of which shows Delta Scuti-type oscillations. Our data consist of differential light curves collected in the filters B and V which have been analysed using the method of Wilson-Devinney (PHOEBE). After identification of an adequate binary model and removal of the best-matching light curve solution, we performed a Fourier analysis of the residual B and V light curves to investigate the pulsational behaviour. We confirm the presence of rapid pulsations with a main period of 27.2 min. Up to eight significant frequencies with semi-amplitudes in the range 3 to 1 mmag were detected, all of which surprisingly lie in the frequency range 43.5-53.5 c\d. This result is independent from the choice of the primary's effective temperature (8200 or 8700 K) since the light curve models for the binary are very similar in both cases. This is yet another case of a complex frequency spectrum observed for an accreting Delta Scuti-type star (after Y Cam). In addition, we demonstrate that the amplitudes of several of these pulsation frequencies show evidence of variability on time scales as short as 1-2 years, perhaps even less. Moreover, our analysis takes into account some recently acquired spectra, from which we obtained the corresponding radial velocities for the years 2007-2009. Investigation of the O-C diagram shows that further monitoring of the epochs of eclipse minima of CT Her will cast a new light on the evolution of its orbital period.Comment: 13 pages, 13 encapsulated Postscript figures. Tables~3, 4, 9 and 12 will be available in electronic form only. Astronomy and Astrophysics, in process (2011). Replaced the abstract with its final versio

Effectiveness of Liraglutide and Lixisenatide in the Treatment of Type 2 Diabetes: Real-World Evidence from The Health Improvement Network (THIN) Database in the United Kingdom.

INTRODUCTION: The glucagon-like peptide-1 receptor agonists liraglutide and lixisenatide are effective at reducing glycated hemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus (T2DM). Although liraglutide has demonstrated superior efficacy in head-to-head clinical trials, real-world evidence of comparative effectiveness is lacking. This observational study aimed to assess the effectiveness of liraglutide versus lixisenatide in UK clinical practice. METHODS: Electronic medical records from The Health Improvement Network (THIN) UK primary care database were analyzed. Patients aged ≥18 years, diagnosed with T2DM, and prescribed liraglutide or lixisenatide between 01 May 2013 and 31 December 2015 were included in the study. Adjusted linear regression models compared the difference in mean change in HbA1c, body mass index (BMI), and systolic blood pressure (SBP) after 12-month follow-up. The proportion of patients achieving glycemic control (HbA1c 1%; and weight reduction ≥3% within 12 months were determined. Cox proportional hazards modeling was used to evaluate the effect of treatment on time to achieving HbA1c and weight reduction targets. Healthcare resource use (HCRU) (GP, secondary care, hospitalizations) was compared using analysis of covariance. RESULTS: The primary outcome was assessed in 579 liraglutide and 213 lixisenatide new users. Fully adjusted linear regression indicated that liraglutide reduced HbA1c significantly more than lixisenatide (mean treatment difference -0.30; 95% CI -0.56, -0.04; p = 0.025). Compared to lixisenatide, liraglutide recipients were 2.5 times more likely to achieve HbA1c 1% HbA1c reduction (HR 1.29; p = 0.0002). BMI and SBP reductions were greater for the liraglutide group but results were not significant. HCRU was comparable between treatment groups. CONCLUSION: These results from the THIN database indicate that liraglutide treatment provided better outcomes related to glycemic control. FUNDING: Novo Nordisk