Molecular and mass spectroscopic analysis of isotopically labeled organic residues

Experimental studies aimed at understanding the evolution of complex organic molecules on interstellar grains were performed. The photolysis of frozen gas mixtures of various compositions containing H2O, CO, NH3, and CH4 was studied. These species were chosen because of their astrophysical importance as deducted from observational as well as theoretical studies of ice mantles on interstellar grains. These ultraviolet photolyzed ices were warmed up in order to produce refractory organic molecules like the ones formed in molecular clouds when the icy mantles are being irradiated and warmed up either by a nearby stellar source or impulsive heating. The laboratory studies give estimates of the efficiency of production of such organic material under interstellar conditions. It is shown that the gradual carbonization of organic mantles in the diffuse cloud phase leads to higher and higher visual absorptivity - yellow residues become brown in the laboratory. The obtained results can be applied to explaining the organic components of comets and their relevance to the origin of life

A retrospective analysis of policy development on compliance with World Health Organization's physical activity recommendations between 2002 and 2005 in European Union adults: Closing the gap between research and policy

© 2018 The Author(s). Background: Physical inactivity (PIA) is a mortality risk factor defined as performing lower levels of physical activity than recommended by the World Health Organization (WHO). After 2002, the WHO released the WHA55.23 Resolution and the Global Strategy which produced several changes in policymaking, but with no subsequent analyses of the impact of these changes in European Union (EU) policymaking while examining PIA prevalence. Methods: PIA of 31,946 adults as a whole sample and country-by-country were analyzed in the 2002 and 2005 EU Special Eurobarometers. PIA prevalence between countries was performed with the χ2 test and PIA between both years and between genders was analyzed with the Z-Score test for two population proportions. A retrospective analysis of national plans was performed to interpret the suitability of such policy documents, considering changes in PIA prevalence. Results: Differences in PIA prevalence were observed between countries (p 0.05). When considering gender, there were no gender reductions in subsamples for Denmark, Finland, Ireland, Portugal, Spain, and United Kingdom, neither in Luxemburg for men, nor in France and Italy for women. When analyzing gender differences across the entire sample, PIA was higher in women than men for both years (p < 0.001). Greece and Luxemburg did not release national plans for promoting physical activity. Conclusions: While large differences in PIA prevalence between EU countries prevailed, the overall PIA descended between both years for the whole sample, men, and women. While this points out a general suitability of policymaking for reducing PIA, not all countries reported reductions in PIA for men, women, or both genders. Also, PIA levels were higher for women in both years, suggesting a less than optimal policy implementation, or lack of women-specific focus across the EU. This analysis helps to identify the strengths and weaknesses of PIA policymaking in the EU and provides researchers with targeted intervention areas for future development

The active living gender's gap challenge: 2013-2017 Eurobarometers physical inactivity data show constant higher prevalence in women with no progress towards global reduction goals

BACKGROUND: The World Health Organization (WHO) considers physical inactivity (PIA) as a critical noncommunicable factor for disease and mortality, affecting more women than men. In 2013, the WHO set a 10% reduction of the PIA prevalence, with the goal to be reached by 2025. Changes in the 2013-2017 period of physical inactivity prevalence in the 28 European Union (EU) countries were evaluated to track the progress in achieving WHO 2025 target. METHODS: In 2013 and 2017 EU Special Eurobarometers, the physical activity levels reported by the International Physical Activity Questionnaire of 53,607 adults were analyzed. Data were considered as a whole sample and country-by-country. A χ2 test was used to analyze the physical inactivity prevalence (%) between countries, analyzing women and men together and separately. Additionally, PIA prevalence was analyzed between years (2013-2017) for the overall EU sample and within-country using a Z-Score for two population proportions. RESULTS: The PIA prevalence increased between 2013 and 2017 for the overall EU sample (p <  0.001), and for women (p = 0.04) and men (p < 0.001) separately. Data showed a higher PIA prevalence in women versus men during both years (p <  0.001). When separately considering changes in PIA by gender, only Belgium's women and Luxembourg's men showed a reduction in PIA prevalence. Increases in PIA prevalence over time were observed in women from Austria, Croatia, Germany, Lithuania, Malta, Portugal, Romania, and Slovakia and in men from Bulgaria, Croatia, Czechia, Germany, Italy, Lithuania, Portugal, Romania, Slovakia, and Spain. CONCLUSIONS: PIA prevalence showed an overall increase across the EU and for both women and men between 2013 and 2017, with higher rates of PIA reported for women versus men during both years. PIA prevalence was reduced in only Belgium's women and Luxembourg's men. Our data indicate a limited gender-sensible approach while tacking PIA prevalence with no progress reaching global voluntary reductions of PIA for 2025

High intensity interval training exercise-induced physiological changes and their potential influence on metabolic syndrome clinical biomarkers: a meta-analysis

Abstract: Background: Despite the current debate about the effects of high intensity interval training (HIIT), HIIT elicits big morpho-physiological benefit on Metabolic Syndrome (MetS) treatment. However, no review or meta-analysis has compared the effects of HIIT to non-exercising controls in MetS variables. The aim of this study was to determine through a systematic review, the effectiveness of HIIT on MetS clinical variables in adults. Methods: Studies had to be randomised controlled trials, lasting at least 3 weeks, and compare the effects of HIIT on at least one of the MetS clinical variables [fasting blood glucose (BG), high-density lipoprotein (HDL-C) triglyceride (TG), systolic (SBP) or diastolic blood pressure (DBP) and waist circumference (WC)] compared to a control group. The methodological quality of the studies selected was evaluated using the PEDro scale. Results: Ten articles fulfilled the selection criteria, with a mean quality score on the PEDro scale of 6.7. Compared with controls, HIIT groups showed significant and relevant reductions in BG (− 0.11 mmol/L), SBP (− 4.44 mmHg), DBP (− 3.60 mmHg), and WC (− 2.26 cm). Otherwise, a slight increase was observed in HDL-C (+ 0.02 mmol/L). HIIT did not produce any significant changes in TG (− 1.29 mmol/L). Conclusions: HIIT improves certain clinical aspects in people with MetS (BG, SBP, DBP and WC) compared to people with MetS who do not perform physical exercise. Plausible physiological changes of HIIT interventions might be related with large skeletal muscle mass implication, improvements in the vasomotor control, better baroreflex control, reduction of the total peripheral resistance, increases in excess post-exercise oxygen consumption, and changes in appetite and satiety mechanisms

Mechanism of an ATP-independent Protein Disaggregase. II. Distinct Molecular Interactions Drive Multiple Steps During Aggregate Disassembly

The ability of molecular chaperones to overcome the misfolding and aggregation of proteins is essential for the maintenance of proper protein homeostasis in all cells. Thus far, the best studied disaggregase systems are the Clp/Hsp100 family of “ATPases associated with various cellular activities” (AAA^+) ATPases, which use mechanical forces powered by ATP hydrolysis to remodel protein aggregates. An alternative system to disassemble large protein aggregates is provided by the 38-kDa subunit of the chloroplast signal recognition particle (cpSRP43), which uses binding energy with its substrate proteins to drive disaggregation. The mechanism of this novel chaperone remains unclear. Here, molecular genetics and structure-activity analyses show that the action of cpSRP43 can be dissected into two steps with distinct molecular requirements: (i) initial recognition, during which cpSRP43 binds specifically to a recognition motif displayed on the surface of the aggregate; and (ii) aggregate remodeling, during which highly adaptable binding interactions of cpSRP43 with hydrophobic transmembrane domains of the substrate protein compete with the packing interactions within the aggregate. This establishes a useful framework to understand the molecular mechanism by which binding interactions from a molecular chaperone can be used to overcome protein aggregates in the absence of external energy input from ATP

Direct visualization reveals dynamics of a transient intermediate during protein assembly

Interactions between proteins underlie numerous biological functions. Theoretical work suggests that protein interactions initiate with formation of transient intermediates that subsequently relax to specific, stable complexes. However, the nature and roles of these transient intermediates have remained elusive. Here, we characterized the global structure, dynamics, and stability of a transient, on-pathway intermediate during complex assembly between the Signal Recognition Particle (SRP) and its receptor. We show that this intermediate has overlapping but distinct interaction interfaces from that of the final complex, and it is stabilized by long-range electrostatic interactions. A wide distribution of conformations is explored by the intermediate; this distribution becomes more restricted in the final complex and is further regulated by the cargo of SRP. These results suggest a funnel-shaped energy landscape for protein interactions, and they provide a framework for understanding the role of transient intermediates in protein assembly and biological regulation

Ferroxitosis: a cell death from modulation of oxidative phosphorylation and PKM2-dependent glycolysis in melanoma

Reliance on glycolysis is a characteristic of malignancy, yet the development of resistance to BRAF inhibitors in melanoma is associated with gain of mitochondrial function. Concurrent attenuation of oxidative phosphorylation and HIF-1α/PKM2-dependent glycolysis promotes a non-apoptotic, iron- and oxygen-dependent cell death that we term ferroxitosis. The redox cycling agent menadione causes a robust increase in oxygen consumption, accompanied by significant loss of intracellular ATP and rapid cell death. Conversely, either hypoxic adaptation or iron chelation prevents menadione-induced ferroxitosis. Ectopic expression of K213Q HIF-1α mutant blunts the effects of menadione. However, knockdown of HIF-1α or PKM2 restores menadione-induced cytotoxicity in hypoxia. Similarly, exposure of melanoma cells to shikonin, a menadione analog and a potential PKM2 inhibitor, is sufficient to induce ferroxitosis under hypoxic conditions. Collectively, our findings reveal that ferroxitosis curtails metabolic plasticity in melanoma

Consensus on a social return on investment model of physical activity and sport: a Delphi study protocol

Background: Physical activity and sport (PAS) have been related to many health outcomes and social benefits. The main aim of this research is to build a Social Return on Investment (SROI) model of PAS based on experts’ opinion to clarify the domains of impact and how to measure and value them. Methods and analysis: A Delphi method will be employed with a systematic review on the SROI framework applied to PAS and initial interviews with experts informing the design of the Delphi survey statements. Three iterative rounds of communication with the expert panel will be carried out. Participants will indicate their level of agreement with each statement on a five-point Likert scale. During the second and third iterative rounds, experts will reappraise the statements and will be provided with a summary of the group responses from the panel. A statement will have reached consensus if ≥70% of the panel agree/strongly agree or disagree/strongly disagree after round 3. Finally, group meetings (3–4 experts) will be conducted to ask about the measurement and valuation methods for each domain. Discussion: The final goal of this project will result in the design of a toolkit for organizations, professionals, and policymakers on how to measure the social benefits of PAS

A modifiable factors-based model for detecting inactive individuals: are the European assessment tools fit for purpose?

BackgroundThe lack of systematic factors affecting physical inactivity (PIA) challenges policymakers to implement evidence-based solutions at a population level. The study utilizes the Eurobarometer to analyse PIA-modifiable variables.MethodsSpecial Eurobarometer 412 physical activity (PA) data were analysed (n = 18 336), including 40 variables along with the International PA Questionnaire. PIA was used as the dependent variable. Variables considered were alternatives to car, places, reasons and barriers to engaging in PA, memberships to clubs and categorical responses about the agreement extent with the area, provision of activities and local governance statements. Logistic regression was used to identify variables contributing to PIA. Beta values (β), standard errors, 95% confidence intervals, the exponentiation for odds ratio and Cox & Snell and Nagelkerke R2 were indicated.ResultsThe resulting model correctly identified 10.7% inactives and 96.9% of actives (R2 of Nagelkerke: 0.153). Variables contributing to the detection of PIA were (P ≤ 0.01): having a disability or an illness, not having friends to do sport with, lacking motivation or interest in and being afraid of injury risk. Additionally, totally agreeing, tend to agree and tend to disagree regarding the extent of local providers offering enough opportunities to be more active also contributed to the model.ConclusionsThe model reported a limited ability to detect modifiable factors affecting PIA, identifying a small percentage of inactive individuals correctly. New questions focused on understanding inactive behaviour are needed to support the European PA public health agenda