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

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

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

Corticospinal Tract Compression by Hematoma in a Patient with Intracerebral Hemorrhage: A Diffusion Tensor Tractography and Functional MRI Study

The purpose of this study was to demonstrate corticospinal tract compression that was due to a hematoma by using diffusion tensor tractography (DTT) and functional MRI (fMRI) in a patient with an intracerebral hemorrhage (ICH). A 23-year-old right-handed woman presented with severe paralysis of her right extremities at the onset of a spontaneous ICH. Over the first three days from onset, the motor function of the affected upper and lower extremities rapidly recovered to the extent that she was able to overcome applied resistance to the affected limbs, and her limbs regained normal function 3 weeks after onset. The tract of the right hemisphere originated from the primary sensori-motor cortex (SM1) and it passed through the known corticospinal tract pathway. However, the tract of the left hemisphere was similar to that of the right hemisphere except that it was displaced to the antero-medial side by the hematoma at the cerebral peduncle. Only the contralateral SM1 area centered on the precentral knob was activated during affected (right) or unaffected (left) hand movements, respectively. In conclusion, fMRI and DTT demonstrated a corticospinal tract compression due to hematoma in this patient. We conclude that the combined use of these two modalities appears to improve the accuracy of investigating the state of the corticospinal tract

The cooperative behaviour of antimicrobial peptides in model membranes

A systematic analysis of the hypothesis of the antimicrobial peptides' (AMPs) cooperative action is performed by means of full atomistic molecular dynamics simulations accompanied by circular dichroism experiments. Several AMPs from the aurein family (2.5,2.6, 3.1), have a similar sequence in the first ten amino acids, are investigated in different environments including aqueous solution, trifluoroethanol (TFE), palmitoyloleoylphosphatidylethanolamine (POPE), and palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayers. It is found that the cooperative effect is stronger in aqueous solution and weaker in TFE. Moreover, in the presence of membranes, the cooperative effect plays an important role in the peptide/lipid bilayer interaction. The action of AMPs is a competition of the hydrophobic interactions between the side chains of the peptides and the hydrophobic region of lipid molecules, as well as the intra peptide interaction. The aureins 2.5-COOH and 2.6-COOH form a hydrophobic aggregate to minimize the interaction between the hydrophobic group and the water. Once that the peptides reach the water/lipid interface the hydrophobic aggregate becomes smaller and the peptides start to penetrate into the membrane. In contrast, aurein 3.1-COOH forms only a transient aggregate which disintegrates once the peptides reached the membrane, and it shows no cooperativity in membrane penetratio