GRB 180620A: Evidence for Late-time Energy Injection

The early optical emission of gamma-ray bursts (GRBs) gives an opportunity to understand the central engine and first stages of these events. About 30% of GRBs present flares whose origin is still a subject of discussion. We present optical photometry of GRB 180620A with the COATLI telescope and RATIR instrument. COATLI started to observe from the end of prompt emission at T + 39.3 s and RATIR from T + 121.4 s. We supplement the optical data with the X-ray light curve from Swift/XRT. We observe an optical flare from T + 110 s to T + 550 s, with a temporal index decay α O,decay = 1.32 ± 0.01, and Δt/t = 1.63, which we interpret as the signature of a reverse shock component. After the initial normal decay the light curves show a long plateau from T + 500 s to T + 7800 s in both X-rays and the optical before decaying again after an achromatic jet break at T + 7800 s. Fluctuations are seen during the plateau phase in the optical. Adding to the complexity of GRB afterglows, the plateau phase (typically associated with the coasting phase of the jet) is seen in this object after the "normal" decay phase (associated with the deceleration phase of the jet), and the jet break phase occurs directly after the plateau. We suggest that this sequence of events can be explained by a rapid deceleration of the jet with t d ≲ 40 s due to the high density of the environment (≈100 cm-3) followed by reactivation of the central engine, which causes the flare and powers the plateau phase

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Can metacognitive interventions improve insight in schizophrenia spectrum disorders? A systematic review and meta-analysis

Background: Patients with schizophrenia spectrum disorders (SSD) tend to lack insight, which is linked to poor outcomes. The effect size of previous treatments on insight changes in SSD has been small. Metacognitive interventions may improve insight in SSD, although this remains unproved. Methods: We carried out a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the effects of metacognitive interventions designed for SSD, namely Metacognitive Training (MCT) and Metacognitive Reflection and Insight Therapy (MERIT), on changes in cognitive and clinical insight at post-treatment and at follow-up. Results: Twelve RCTs, including 10 MCT RCTs (n = 717 participants) and two MERIT trials (n = 90), were selected, totalling N = 807 participants. Regarding cognitive insight six RCTs (n = 443) highlighted a medium effect of MCT on self-reflectiveness at post-treatment, d = 0.46, p < 0.01, and at follow-up, d = 0.30, p < 0.01. There was a small effect of MCT on self-certainty at post-treatment, d = −0.23, p = 0.03, but not at follow-up. MCT was superior to controls on an overall Composite Index of cognitive insight at post-treatment, d = 1.11, p < 0.01, and at follow-up, d = 0.86, p = 0.03, although we found evidence of heterogeneity. Of five MCT trials on clinical insight (n = 244 participants), which could not be meta-analysed, four of them favoured MCT compared v. control. The two MERIT trials reported conflicting results. Conclusions: Metacognitive interventions, particularly Metacognitive Training, appear to improve insight in patients with SSD, especially cognitive insight shortly after treatment. Further long-term RCTs are needed to establish whether these metacognitive interventions-related insight changes are sustained over a longer time period and result in better outcomes

Reliability and validity of three questionnaires measuring context-specific sedentary behaviour and associated correlates in adolescents, adults and older adults

BACKGROUND: Reliable and valid measures of total sedentary time, context-specific sedentary behaviour (SB) and its potential correlates are useful for the development of future interventions. The purpose was to examine test-retest reliability and criterion validity of three newly developed questionnaires on total sedentary time, context-specific SB and its potential correlates in adolescents, adults and older adults. METHODS: Reliability and validity was tested in six different samples of Flemish (Belgium) residents. For the reliability study, 20 adolescents, 22 adults and 20 older adults filled out the age-specific SB questionnaire twice. Test-retest reliability was analysed using Kappa coefficients, Intraclass Correlation Coefficients and/or percentage agreement, separately for the three age groups. For the validity study, data were retrieved from 62 adolescents, 33 adults and 33 older adults, with activPAL as criterion measure. Spearman correlations and Bland-Altman plots (or non-parametric approach) were used to analyse criterion validity, separately for the three age groups and for weekday, weekend day and average day. RESULTS: The test-retest reliability for self-reported total sedentary time indicated following values: ICC = 0.37-0.67 in adolescents; ICC = 0.73-0.77 in adults; ICC = 0.68-0.80 in older adults. Item-specific reliability results (e.g. context-specific SB and its potential correlates) showed good-to-excellent reliability in 67.94%, 68.90% and 66.38% of the items in adolescents, adults and older adults respectively. All items belonging to sedentary-related equipment and simultaneous SB showed good reliability. The sections of the questionnaire with lowest reliability were: context-specific SB (adolescents), potential correlates of computer use (adults) and potential correlates of motorized transport (older adults). Spearman correlations between self-reported total sedentary time and the activPAL were different for each age group: rho = 0.02-0.42 (adolescents), rho = 0.06-0.52 (adults), rho = 0.38-0.50 (older adults). Participants over-reported total sedentary time (except for weekend day in older adults) compared to the activPAL, for weekday, weekend day and average day respectively by +57.05%, +46.29%, +53.34% in adolescents; +40.40%, +19.15%, +32.89% in adults; +10.10%, -6.24%, +4.11% in older adults. CONCLUSIONS: The questionnaires showed acceptable test-retest reliability and criterion validity. However, over-reporting of total SB was noticeable in adolescents and adults. Nevertheless, these questionnaires will be useful in getting context-specific information on SB

A pilot 1-year follow-up randomised controlled trial comparing metacognitive training to psychoeducation in schizophrenia: effects on insight

Poor insight in schizophrenia spectrum disorders (SSD) is linked with negative outcomes. This single-centre, assessor-blind, parallel-group 1-year follow-up randomised controlled trial (RCT) tested whether metacognitive training (MCT) (compared to psychoeducation) may improve insight and outcomes in outpatients with SSD assessed: at baseline (T0); after treatment (T1) and at 1-year follow-up (T2). Insight (primary outcome) was measured with (i) the Schedule for Assessment of Insight-Expanded version- (SAI-E), including illness recognition (IR), symptom relabelling (SR), treatment compliance (TC) and total insight scores (TIS); and (ii) the Beck Cognitive Insight Scale (BCIS). Between-group comparisons were nonsignificant, while within the MCT group (but not within controls) there was a significant medium effect size for improved TIS at T2 (d = 0.67, P = 0.02). Secondary outcomes included cognitive measures: Jumping to Conclusions (JTC), Theory of Mind (ToM), plus symptom severity and functioning. Compared to psychoeducation, MCT improved the PANSS excitement (d = 1.21, P = 0.01) and depressed (d = 0.76, P = 0.05) factors at T2; and a JTC task both at T1 (P = 0.016) and at T2 (P = 0.031). Participants in this RCT receiving MCT showed improved insight at 1-year follow-up, which was associated with better mood and reduced JTC cognitive bias. In this pilot study, no significant benefits on insight of MCT over psychoeducation were detected, which may have been due to insufficient power

Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

Silvopastoral systems as a tool for territorial sustainability and biodiversity

Rural and livestock population evolution in the inner north of Portugal has demonstrated a great regression with consequences for environment and nature conservation. In this context, and taking into account that pastoral activity has shaped the natural areas of mountain territories since its beginning and that territories are currently part of Natura 2000 network, rethinking the importance of such activity has become vital. The constraints affecting daily tasks performed by shepherds and livestock breeders as well as the installed social segregation are a strong limitation. However, current research developed in the context of nature conservation has demonstrated the importance of the landscape mosaic promoted by grazing in the preservation of priority habitats. In this way, it is urgent to assess the issue of shepherds and livestock breeders’ image in terms of their roles, relationships and concerns, as well as to assess pastoralism socioeconomics in regard to self-consumption, market and rural self-sufficiency. In this perspective, this work presents an analysis of the adaptation of grazing to current times, perceiving its limitations and success potential.This work is supported by European Structural and Investment Funds, FEDER component, through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) [Project No. 006971 (UID/SOC/04011)], and national funds, through FCT, Portuguese Foundation for Science and Technology under project UID/SOC/04011/2013.info:eu-repo/semantics/publishedVersio

SECRET domain of variola virus CrmB protein can be a member of poxviral type II chemokine-binding proteins family

<p>Abstract</p> <p>Background</p> <p>Variola virus (VARV) the causative agent of smallpox, eradicated in 1980, have wide spectrum of immunomodulatory proteins to evade host immunity. Recently additional biological activity was discovered for VARV CrmB protein, known to bind and inhibit tumour necrosis factor (TNF) through its N-terminal domain homologous to cellular TNF receptors. Besides binding TNF, this protein was also shown to bind with high affinity several chemokines which recruit B- and T-lymphocytes and dendritic cells to sites of viral entry and replication. Ability to bind chemokines was shown to be associated with unique C-terminal domain of CrmB protein. This domain named SECRET (Smallpox virus-Encoded Chemokine Receptor) is unrelated to the host proteins and lacks significant homology with other known viral chemokine-binding proteins or any other known protein.</p> <p>Findings</p> <p><it>De novo </it>modelling of VARV-CrmB SECRET domain spatial structure revealed its apparent structural homology with cowpox virus CC-chemokine binding protein (vCCI) and vaccinia virus A41 protein, despite low sequence identity between these three proteins. Potential ligand-binding surface of modelled VARV-CrmB SECRET domain was also predicted to bear prominent electronegative charge which is characteristic to known orthopoxviral chemokine-binding proteins.</p> <p>Conclusions</p> <p>Our results suggest that SECRET should be included into the family of poxviral type II chemokine-binding proteins and that it might have been evolved from the vCCI-like predecessor protein.</p

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form