Protection Against Marburg Virus Using a Recombinant VSV-Vaccine Depends on T and B Cell Activation

Marburg virus (MARV) is the causative agent of hemorrhagic fever outbreaks with high case fatality rates. Closely related to Ebola virus, MARV is a filamentous virus with a negative-sense, single-stranded RNA genome. Although extensive studies on filovirus countermeasures have been conducted, there are no licensed treatments against MARV infections. An experimental vaccine based on the recombinant vesicular stomatitis virus (VSV) expressing the MARV-Musoke glycoprotein demonstrated complete protection when a single dose was administered 28 days and up to 14 months prior to MARV challenge. Here, we analyzed the protective efficacy of an updated vaccine expressing the MARV-Angola glycoprotein (VSV-MARV). A single dose of VSV-MARV given 5 weeks before challenge provided uniform protection with no detectable viremia. The vaccine induced B and T cell proliferation and, importantly, antigen-specific IgG production. Transcriptomic signatures confirm these findings and suggest innate immunity engendered by VSV-MARV may direct the development of protective humoral immunity

The impact of exposure to cartoons promoting healthy eating on children's food preferences and choices

Objective: This study explored whether a cartoon show with healthy eating messages positively affected children's food choices and food preferences.Design: Experimental between-subjects design.Setting: Four elementary schools in Portugal were investigated.Participants: Children (aged 4-8 years; n = 142) were randomly assigned to 1 of 2 groups: a comparison group (n = 73) was exposed to cartoons with no reference to food and an intervention group (n = 69) was exposed to cartoons with healthy eating messages. After viewing, each child was given the opportunity to eat ad libitum for 10 minutes from a small selection of snack foods.Main Outcome Measure: Number of healthy and unhealthy food items chosen. Food preferences were measured using an adapted version of the Leeds Food Preference Checklist.Analysis: Generalized linear models were used to test for differences between groups. Results were considered significant at P <= .05.Results: Children in the experimental group chose significantly more healthy food items than did those in the comparison group (B = -.600; SE = .19; P < .05).Conclusions and Implications: Future studies may address the effect of prolonged exposure to healthy eating cartoons. Cartoons can be used to promote healthy food choices and can be a part of health promotion campaigns.This research was partially supported by Fundacao para a Ciencia e Tecnologia through a European Union COMPETE program grant to Eva Conceicao (IF/01219/2014), and a postdoctoral scholarship (SFRH/BPD/94490/2013) to Ana Rita Vaz, cofinanced by FEDER under the PT2020 Partnership Agreement (UID/PSI/01662/2013) and the project PTDC/MHC-PCL/4974/2012. This research was supported, in part, by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology, and Higher Education through national funds and cofinanced by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). The authors would like to thank Nutri Ventures for adapting the episodes for the research purposes. They would also like to thank Ana Rito for her suggestions regarding the study protocol

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

Background: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. Methods: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. Findings: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies. Interpretation: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. Funding: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

The Influence of Personality Traits on Reported Adherence to Medication in Individuals with Chronic Disease: An Epidemiological Study in West Sweden

BACKGROUND: Limited research exists exploring the influence of personality on adherence behaviour. Since non-adherence is a major obstacle in treating prevalent chronic diseases the aim was to determine whether personality traits are related to reported adherence to medication in individuals with chronic disease. METHODOLOGY/PRINCIPAL FINDINGS: Individuals with chronic disease (n = 749) were identified in a random population sample of 5000 inhabitants aged 30-70 in two municipalities in West Sweden. Data on five personality traits, Neuroticism, Extraversion, Openness to experiences, Agreeableness, and Conscientiousness, and medication adherence behaviour was collected by questionnaires. Statistical analyses resulted in a negative relationship between Neuroticism and medication adherence (P < 0.001), while both Agreeableness (P < 0.001) and Conscientiousness (P < 0.001) were positively related to adherence. At high levels of Conscientiousness, low adherence was related to higher scores in Neuroticism. At high levels of Agreeableness, low adherence was related to low scores in Conscientiousness and high scores in Openness to experiences. CONCLUSIONS: This study demonstrated that multiple personality traits are of significant importance for adherence behaviour in individuals with chronic disease. The findings suggest that several personality traits may interact in influencing adherence behaviour. Personality traits could putatively be used to focus efforts to educate and support patients with high risk of low medical adherence

Characterization of a Novel Interaction between Bcl-2 Members Diva and Harakiri

Interactions within proteins of the Bcl-2 family are key in the regulation of apoptosis. The death-inducing members control apoptotic mechanisms partly by antagonizing the prosurvival proteins through heterodimer formation. Structural and biophysical studies on these complexes are providing important clues to understand their function. To help improve our knowledge on protein-protein interactions within the Bcl-2 family we have studied the binding between two of its members: mouse Diva and human Harakiri. Diva has been shown to perform both prosurvival and killing activity. In contrast, Harakiri induces cell death by interacting with antiapoptotic Bcl-2 members. Here we show using ELISA and NMR that Diva and Harakiri can interact in vitro. Combining the NMR data with the previously reported three-dimensional structure of Diva we find that Harakiri binds to a specific region in Diva. This interacting surface is equivalent to the known binding area of prosurvival Bcl-2 members from the reported structures of the complexes, suggesting that Diva could function at the structural level similarly to the antiapoptotic proteins of the Bcl-2 family. We illustrate this result by building a structural model of the heterodimer using molecular docking and the NMR data as restraints. Moreover, combining circular dichroism and NMR we also show that Harakiri is largely unstructured with residual (13%) α-helical conformation. This result agrees with intrinsic disorder previously observed in other Bcl-2 members. In addition, Harakiri constructs of different length were studied to identify the region critical for the interaction. Differential affinity for Diva of these constructs suggests that the amino acid sequence flanking the interacting region could play an important role in binding

Intrinsic Order and Disorder in the Bcl-2 Member Harakiri: Insights into Its Proapoptotic Activity

Harakiri is a BH3-only member of the Bcl-2 family that localizes in membranes and induces cell death by binding to prosurvival Bcl-xL and Bcl-2. The cytosolic domain of Harakiri is largely disorder with residual α-helical conformation according to previous structural studies. As these helical structures could play an important role in Harakiri's function, we have used NMR and circular dichroism to fully characterize them at the residue-atomic level. In addition, we report structural studies on a peptide fragment spanning Harakiri's C-terminal hydrophobic sequence, which potentially operates as a transmembrane domain. We initially checked by enzyme immunoassays and NMR that peptides encompassing different lengths of the cytosolic domain are functional as they bind Bcl-xL and Bcl-2. The structural data in water indicate that the α-helical conformation is restricted to a 25-residue segment comprising the BH3 domain. However, structure calculation was precluded because of insufficient NMR restraints. To bypass this problem we used alcohol-water mixture to increase structure population and confirmed by NMR that the conformation in both milieus is equivalent. The resulting three-dimensional structure closely resembles that of peptides encompassing the BH3 domain of BH3-only members in complex with their prosurvival partners, suggesting that preformed structural elements in the disordered protein are central to binding. In contrast, the transmembrane domain forms in micelles a monomeric α-helix with a population close to 100%. Its three-dimensional structure here reported reveals features that explain its function as membrane anchor. Altogether these results are used to propose a tentative structural model of how Harakiri works

Having a creative day:understanding entrepreneurs’ daily idea generation through a recovery lens

Prior research has shown that trait creativity is important for becoming an entrepreneur and successful in business. We explore a new perspective by investigating how recovery from work stress influences entrepreneurs’ daily idea generation, a key aspect of creativity. Physio-logical and mental recovery enables the cognitive processes of creative problem-solving. Moreover, differences in mental recovery processes help to explain age-related changes in en-trepreneurs’ creativity. Multilevel analyses based on 415 daily data from 62 entrepreneurs support our predictions. Our study introduces a new “state” perspective to understanding en-trepreneurs’ creativity, and highlights the critical role of recovery processes for idea genera-tion