On the source of Faraday rotation in the jet of the radio galaxy 3C120

The source of Faraday rotation in the jet of the radio galaxy 3C120 is analyzed through Very Long Baseline Array observations carried out between 1999 and 2007 at 86, 43, 22, 15, 12, 8, 5, 2, and 1.7 GHz. Comparison of observations from 1999 to 2001 reveals uncorrelated changes in the linear polarization of the underlying jet emission and the Faraday rotation screen: while the rotation measure (RM) remains constant between approximately 2 and 5 mas from the core, the RM-corrected electric vector position angles (EVPAs) of two superluminal components are rotated by almost 90 degrees when compared to other components moving through similar jet locations. On the other hand, the innermost 2 mas experiences a significant change in RM -- including a sign reversal -- but without variations in the RM-corrected EVPAs. Similarly, observations in 2007 reveal a double sign reversal in RM along the jet, while the RM-corrected EVPAs remain perpendicular to the jet axis. Although the observed coherent structure and gradient of the RM along the jet supports the idea that the Faraday rotation is produced by a sheath of thermal electrons that surrounds the emitting jet, the uncorrelated changes in the RM and RM-corrected EVPAs indicate that the emitting jet and the source of Faraday rotation are not closely connected physically and have different configurations for the magnetic field and/or kinematical properties. Furthermore, the existence of a region of enhanced RM whose properties remain constant over three years requires a localized source of Faraday rotation, favoring a model in which a significant fraction of the RM originates in foreground clouds.Comment: 12 pages, 11 figures; Accepted for publication in Ap

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk-outcome associations. METHODS: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Stanaway JD, Afshin A, Gakidou E, et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1923-1994.Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd

Comparative kinetic characterization of the activity of glycosylated and non-glycosylated trypsin-like serine protease isolated from adults of Rhyzopertha dominica (Coleoptera: Bostrichidae) reared on the grain of three different cultivars of wheat

Rhyzopertha dominica is a pest that uses trypsin-like serine protease enzymes to hydrolyse the proteins in the cereal grains on which it feeds. The present study reveals for the first time that that there are both glycosylated and non-glycosylated serine proteases. The progeny of R. dominica reared on the grain three varieties of wheat were used to fractionate their trypsin-like serine proteases using Concanavalin A affinity chromatography. The albumin fractions from the wheat cultivars used in this study were subjected to size exclusion chromatography to fractionate the albumin inhibitors that are highly specific for the serine protease activity of R. dominica. Kinetic and thermodynamic assays were used to differentiate both types of enzymes. In general, the catalytic efficiency values Vmax/Km for glycosylated proteases were higher, indicating that glycosylation increases the affinity for the substrate. Inhibition assays using wheat albumins revealed that the glycosylated enzymes had higher Ki values, indicating a low affinity for the inhibitors than the non-glycosylated enzymes. Thermodynamic analysis indicates that glycosylation increases the activation energy Ea improving the serine proteases' catalysis. Thus it is likely that R. dominica uses glycosylated proteases in order to optimize the hydrolysis of cereal proteins and nullify the action of wheat grain protease inhibitors and increase its chances of survival

Malfunctioning of the iron-sulfur cluster assembly machinery in Saccharomyces cerevisiae produces oxidative stress via an iron-dependent mechanism, causing dysfunction in respiratory complexes.

Biogenesis and recycling of iron-sulfur (Fe-S) clusters play important roles in the iron homeostasis mechanisms involved in mitochondrial function. In Saccharomyces cerevisiae, the Fe-S clusters are assembled into apoproteins by the iron-sulfur cluster machinery (ISC). The aim of the present study was to determine the effects of ISC gene deletion and consequent iron release under oxidative stress conditions on mitochondrial functionality in S. cerevisiae. Reactive oxygen species (ROS) generation, caused by H2O2, menadione, or ethanol, was associated with a loss of iron homeostasis and exacerbated by ISC system dysfunction. ISC mutants showed increased free Fe2+ content, exacerbated by ROS-inducers, causing an increase in ROS, which was decreased by the addition of an iron chelator. Our study suggests that the increment in free Fe2+ associated with ROS generation may have originated from mitochondria, probably Fe-S cluster proteins, under both normal and oxidative stress conditions, suggesting that Fe-S cluster anabolism is affected. Raman spectroscopy analysis and immunoblotting indicated that in mitochondria from SSQ1 and ISA1 mutants, the content of [Fe-S] centers was decreased, as was formation of Rieske protein-dependent supercomplex III2IV2, but this was not observed in the iron-deficient ATX1 and MRS4 mutants. In addition, the activity of complexes II and IV from the electron transport chain (ETC) was impaired or totally abolished in SSQ1 and ISA1 mutants. These results confirm that the ISC system plays important roles in iron homeostasis, ROS stress, and in assembly of supercomplexes III2IV2 and III2IV1, thus affecting the functionality of the respiratory chain

Kinetics of ROS generation in suspensions of <i>S. cerevisiae ISC</i> mutants treated with stressors.

<p>Yeast cultures were grown in liquid YPD medium without stressors and harvested in late exponential growth phase. Yeast YPD-grown cultures were incubated for 2 h with the respective ROS probe; then, the suspensions were treated with and without stressor (H₂O₂ 12 mM, menadione 80 µM, and ethanol 10%), incubated at 30°C with light shaking. Samples (100 µL) were taken and suspended in PBS buffer for determination of intracellular ROS levels by real-time analysis in a flow cytometer. A–F) Results represent the percentage of cells that showed positive fluorescence. Yeast suspensions without a stressor (dashed lines) and with a stressor treatment (continuous lines). The ROS fluorescent probes DHE (O₂^•− indicators) and DHR123 (mitochondrial ROS in general, mainly a H₂O₂ indicator) were used. A–C) Fluorescence determination using DHE probe, D–F) fluorescence determination using DHR123 probe. Values are the mean of three independent experiments with 20,000 cells counted by flow cytometry per each point. SEM values are indicated as bars (n = 3), one-way ANOVA was used to compare mutants versus to WT. Significant differences (<i>p</i><0.05) are indicated with (*).</p

Model proposed for the mechanism of mitochondrial generation of ROS dependent on free Fe²⁺ release from Fe–S-containing proteins in <i>S. cerevisiae</i>.

<p>The [2Fe–2S] commonly carried by the multi-protein complex (Ssq1-Jac1-Mge1-Grx5) can also be assembled into recipient apoproteins, such as the Rieske protein of cytochrome <i>bc1</i> from respiratory complex III. The Isa1 and Iba57 proteins may function as iron reservoirs, from which the metal can subsequently be transferred to [Fe–S] centers or heme prosthetic groups from cytochrome <i>bc₁</i>. When superoxide (O₂^•−) is generated by electron leaking in the ETC, and other ROS are produced by oxidative metabolism or by oxidant agents, the [4Fe–4S], [3Fe–4S], or [2Fe–2S] clusters contained in the ETC complexes are disrupted. This event provokes a generalized uncoupling/denaturation of Fe–S proteins, causing a release and thus an increment in the iron labile pool (Fe²⁺), which increases mitochondrial ROS levels via the Fenton and Haber–Weiss reactions. If the ISC assembly system is dysfunctional, supercomplex (III₂IV₂) formation is affected, as is [Fe–S] recycling, provoking ETC dysfunction. Hence, the levels of ROS generation increase in an additive manner by a vicious circle of disruption of iron-containing or iron storage proteins, causing an imbalanced ROS content (increment of species such as H₂O₂ and superoxide species), that provokes mitochondrial dysfunction and may ultimately lead to apoptotic events.</p

Analyses of the functionality of mitochondrial respiratory chain complexes in <i>S. cerevisiae ISC</i> mutants.

<p>Mitochondrial functionality was evaluated in mitochondrial suspensions obtained from cultures grown in liquid YPD medium, cells were harvested in the late exponential growth phase, mitochondria were isolated and re-suspended in the appropriate buffer, and mitochondrial activities were measured as described in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111585#s2" target="_blank">Materials and Methods</a>. A) membrane potential, B) activity of succinate-DCIP oxidoreductase, C) activity of succinate-cytochrome <i>c</i> oxidoreductase, D) activity of glycerol-cytochrome <i>c</i> oxidoreductase, E) activity of L-lactate-cytochrome <i>c</i> oxidoreductase, and F) activity of cytochrome <i>c</i> oxidase. Values are the mean of three independent experiments. SE values are indicated as bars (n = 3), one-way ANOVA with Tukey's post-hoc test was used to compare yeast strains, and significant differences (<i>p</i><0.05) are indicated with different lowercase letters.</p