Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk.

Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.

Seasonal and diel modulation of DOM in a mangrove-dominated estuary.

Rivers and estuaries are the main links between continents and oceans. The Paraíba do Sul River is among the most important rivers of the southeastern Brazilian region, carrying an average of 0.08 Tg of dissolved organic matter (DOM) to the ocean but has been facing significant changes in river discharge. In this study, we aimed to provide insights into the sources and transformations of chromophoric dissolved organic matter (CDOM) and fluorescent dissolved organic matter (FDOM) sources across a salinity gradient under changing river discharge scenarios. Three spatial surveys were performed covering the entire salinity gradient of the main estuarine channel and surrounding mangrove waters under contrasting river discharge (178 to 1240 m3 s-1), and diel sampling was conducted in the mangrove tidal creek. The characterization of DOM through the parallel factor analysis (PARAFAC) model identified six components across the river-ocean gradient and mangrove creek: terrestrial origin (C1 - fulvic acid and C2 and C3 - humic-like), protein-like (C4), tryptophan-like (C5), and tyrosine-like (C6). Our results showed a shift in DOM composition and contribution along the salinity gradient, from terrestrial (C3) to autochthonous (C5 and C6) signatures. The October-17 dry campaign was characterized by a higher proportion of microbial protein-like component C4 and a lower contribution of humic-like components compared to February-17 and March-18 across the salinity gradient with an increase in the mixing zone. The DOM compositions of the February 17 dry and March 18 wet campaigns were similar. Additionally, the March-18 wet campaign, marked by the highest river discharge, showed higher inputs of terrestrial DOM (C1-C3 components) compared to February-17 in the estuary, which allowed DOM to be transported rather than transformed. The mangrove diel study showed that tidal fluctuations are also an important driver of carbon input to the mangrove creek with a possible impact on DOM composition in estuarine waters.

The interface between coronaviruses and host cell RNA biology: Novel potential insights for future therapeutic intervention.

Coronaviruses, including SARS-Cov-2, are RNA-based pathogens that interface with a large variety of RNA-related cellular processes during infection. These processes include capping, polyadenylation, localization, RNA stability, translation, and regulation by RNA binding proteins or noncoding RNA effectors. The goal of this article is to provide an in-depth perspective on the current state of knowledge of how various coronaviruses interact with, usurp, and/or avoid aspects of these cellular RNA biology machineries. A thorough understanding of how coronaviruses interact with RNA-related posttranscriptional processes in the cell should allow for new insights into aspects of viral pathogenesis as well as identify new potential avenues for the development of anti-coronaviral therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Redes de profesionales en la prevención y el abordaje de la obesidad infantil / Professionals’ nets for the prevention and management of children obesity

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An experimental approach to investigate mercury species transformations under redox oscillations in coastal sediments.

This work describes a laboratory experiment designed to unravel mercury species reactivity in superficial coastal sediments oscillating between oxic and anoxic conditions. The experimental set-up has been applied to a sediment slurry from the Arcachon Bay (France) to follow the evolution of both naturally occurring (i.e. endogenous) and isotopically enriched added mercury species (i.e. exogenous, ¹99IHg and ²°¹MMHg) at environmental levels. The transformation and partition between the different phases (aqueous, solid and gaseous) of the endogenous and exogenous mercury species (inorganic Hg (IHg), monomethyl Hg (MMHg), elemental Hg (Hg°) and dimethyl Hg (DMHg)) have been investigated by isotopic speciation methods throughout the experiment. The results demonstrate that the experimental approach is able to promote sediment redox oscillations and to simultaneously follow the biogeochemical fate of naturally occurring or added mercury species. Experimentally driven redox transition events were found to significantly enhance the aqueous Hg species concentrations, while the MMHg burden is not greatly affected. Indeed, during the anoxic-oxic transition, while aqueous endogenous IHg and MMHg exhibited a two-fold increase, aqueous exogenous IHg and MMHg increased 7 and 4 times, respectively. Transient increases of the net IHg methylation were recorded during the redox transitions with the largest increase of the MMHg contents (factor 1.8) observed during the oxic-anoxic transition. High resolution in situ redox experiments have not been performed up to now, therefore the developed experimental set-up provides novel insights in both the influence of redox conditions on Hg methylation/demethylation and adsorption/desorption processes and kinetics in superficial sediments.

The role of thermal coupling on avalanches in manganites.

We report here a study on the environmental dependence of the occurrence, at low temperature, of ultra-sharp field induced avalanches in phase separated manganites. Despite the high reproducibility of avalanches, it has already been observed that the critical fields shift with the magnetic field sweep rate and that different sample sizes lead to different ignition fields for the avalanches. Critical growing rates have been suggested to describe the avalanche ignition though the role of thermal coupling has hardly been considered. We qualitatively analyze here a set of experimental data on avalanches in manganites and discuss the role of thermal coupling as a key parameter of the instability in a dynamical system.

Speciation of mercury in a fluid mud profile of a highly turbid macrotidal estuary (Gironde, France).

Mercury (Hg) speciation and partitioning have been investigated in a fluid mud profile collected in the high turbidity zone of the Gironde estuary. The formation of the fluid lens generates local and transient oxic-anoxic oscillations following the sedimentation-resuspension tidal cycles under a specific hydrodynamic regime. The total Hg concentration, ranging from 5 to 190 nM, increases with SPM concentration (4-174 g L-1) to a maximum at bottom. Particulate Hg averages 99% of total Hg. Particulate inorganic Hg (IHg(II)P) and monomethyl Hg (MMHgP) exhibit a similar trend: the maximum concentration is observed within the upper layer above the depth of 7 m and the minimum at the bottom layers of the fluid mud. Significant levels of "dissolved" (i.e. filter passing) Hg species (IHg(II)D, HgoD, MMHgD, DMHgD) are observed within the redox transition interface. In the sub/anoxic fluid mud layer, increasing concentrations of IHg(II)D and MMHgD coincide with decreasing concentrations of IHg(II)P and MMHgP, respectively. The distribution coefficient (log Kd) between the "dissolved" and particulate fraction for IHg(II) averages 4.5 +/- 0.2. A Kd minimum for IHg(II) is observed in the surface layer and at the bottom of the fluid mud and coincides with the maximum levels of dissolved Mn and Fe. Log Kd for MMHg averages 3.3 +/- 0.9 and presents the highest values (4.3-4.6) in the surface and the lowest (approximately 2.2) at bottom, corresponding to the particulate carbon profile. These results demonstrate that the fate of IHg(II) and MMHg in the fluid mud system is influenced by the redox cycling of major species such as carbon, Fe, and Mn. It is therefore suggested that the redox oscillations generated by fluid mud formation in the high turbidity zone affect the distribution and transfer of Hg species in macrotidal estuaries.

Nitrogen-alkalinity interactions in the highly polluted Scheldt basin (Belgium).

We present results of one year observations in highly heterotrophic and oxygen-depleted rivers of the polluted Scheldt basin. Monthly measurements revealed a high variability for dissolved inorganic carbon and nitrogen, with the following strong parallelism: highest alkalinity and NH4+ were associated with lowest NO3- and oxygen and vice-versa. In river water incubations, nitrification lowered the alkalinity whereas denitrification raised it; in an anoxic, NO3(-)-free incubation an increase of alkalinity was observed, partially due to ammonification. A stoichiometric analysis, taking into account the amount of protons produced or consumed by each process involving nitrogen, revealed that monthly variations of NO3- and NH4+ with ammonification, nitrification and denitrification could explain the 28 and 62% alkalinity variations at all stations, except one. The remaining part of the alkalinity variations was attributed to other anaerobic processes (Mn-, Fe- and SO4-reductions). This trend seems to be the result of the whole catchment metabolism (riverine waters and sediments, sewage networks and agricultural soils). The observed HCO3- concentrations in the Scheldt basin were 2-10 times higher than the representative concentrations reported in pristine basins and used in chemical weathering models. This suggests the existence of an anthropogenic source, originating from organic matter decomposition. We conclude that in highly polluted basins, nitrogen transformations strongly influence the acid-base properties of water.

Carbon dioxide emission from european estuaries

The partial pressure of carbon dioxide (pCO2) in surface waters and related atmospheric exchanges were measured in nine European estuaries. Averaged fluxes over the entire estuaries are usually in the range of 0.1 to 0.5 mole of CO2 per square meter per day. For wide estuaries, net daily fluxes to the atmosphere amount to several hundred tons of carbon (up to 790 tons of carbon per day in the Scheldt estuary). European estuaries emit between 30 and 60 million tons of carbon per year to the atmosphere, representing 5 to 10% of present anthropogenic CO2 emissions for Western Europe.