Mercury inputs to Great Salt Lake, Utah: Reconnaissance-Phase results

In response to increasing public concern regarding mercury (Hg) cycling in Great Salt Lake (GSL) ecosystem, a series of studies were initiated to differentiate between the mass of Hg from riverine versus atmospheric sources to GSL. Cumulative riverine Hg load to GSL during a 1 year time period (April 1, 2007 to March 31, 2008) was 6 kg, with almost 50% of the cumulative Hg load contributed by outflow from Farmington Bay. Comparison of cumulative annual atmospheric Hg deposition (32 kg) to annual riverine deposition (6 kg) indicates that atmospheric deposition is the dominant input source to GSL. A sediment core collected from the southern arm of GSL was used to reconstruct annual Hg deposition rates over the past ~ 100 years. Unlike most freshwater lakes, small changes in water level in GSL significantly changes the lake surface area available for direct deposition of atmospheric Hg. There is good agreement between lake elevation (and corresponding lake surface area) and Hg deposition rates estimated from the sediment core. Higher lake levels, combined with sediment focusing processes, result in an increase in Hg accumulation rates observed in the sediment core. These same combination of processes are responsible for the lower Hg accumulation rates observed in the sediment core during historic low stands of GSL

The genetic etiology of periodic limb movement in sleep

Study Objectives Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects. Methods The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization. Results We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 x 10(-12), beta = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14);and rs9369062 (p = 3.06 x 10(-22), beta = 0.2093), a SNP located in the intron region of BTBD9 (6p12);both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS. Conclusions Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings

Granzyme K mediates IL-23-dependent inflammation and keratinocyte proliferation in psoriasis

Psoriasis is an inflammatory disease with systemic manifestations that most commonly presents as itchy, erythematous, scaly plaques on extensor surfaces. Activation of the IL-23/IL-17 pro-inflammatory signaling pathway is a hallmark of psoriasis and its inhibition is key to clinical management. Granzyme K (GzmK) is an immune cell-secreted serine protease elevated in inflammatory and proliferative skin conditions. In the present study, human psoriasis lesions exhibited elevated GzmK levels compared to non-lesional psoriasis and healthy control skin. In an established murine model of imiquimod (IMQ)-induced psoriasis, genetic loss of GzmK significantly reduced disease severity, as determined by delayed plaque formation, decreased erythema and desquamation, reduced epidermal thickness, and inflammatory infiltrate. Molecular characterization in vitro revealed that GzmK contributed to macrophage secretion of IL-23 as well as PAR-1-dependent keratinocyte proliferation. These findings demonstrate that GzmK enhances IL-23-driven inflammation as well as keratinocyte proliferation to exacerbate psoriasis severity

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue

Equilibrium gas-phase structures of sodium fluoride, bromide, and iodide monomers and dimers

The alkali halides sodium fluoride, sodium bromide, and sodium iodide exist in the gas phase as both monomer and dimer species. A reanalysis of gas electron diffraction (GED) data collected earlier has been undertaken for each of these molecules using the EXPRESS method to yield experimental equilibrium structures. EXPRESS allows amplitudes of vibration to be estimated and correction terms to be applied to each pair of atoms in the refinement model. These quantities are calculated from the ab initio potential-energy surfaces corresponding to the vibrational modes of the monomer and dimer. Because they include many of the effects associated with large-amplitude modes of vibration and anharmonicity, we have been able to determine highly accurate experimental structures. These results are found to be in good agreement with those from high-level core-valence ab initio calculations and are substantially more precise than those obtained in previous structural studies

Large meta-analysis of genome-wide association studies identifies five loci for lean body mass (vol 8, 80, 2017)

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Forecasting the Nasdaq-100 index using GRU and ARIMA

Today, there is an overwhelming amount of data that is being collected when it comes to financial markets. For forecasting stock indexes, many models rely only on historical values of the index itself. One such model is the ARIMA model. Over the last decades, machine learning models have challenged the classical time series models, such as ARIMA. The purpose of this thesis is to study the ability to make predictions based solely on the historical values of an index, by using a certain subset of machine learning models: a neural network in the form of a Gated Recurrent Unit (GRU). The GRU model’s ability to predict a financial market is compared to the ability of a simple ARIMA model. The financial market that was chosen to make the comparison was the American stock index Nasdaq-100, i.e., an index of the 100 largest non-financial companies on NASDAQ. Our results indicate that GRU is unable to outperform ARIMA in predicting the Nasdaq-100 index. For the evaluation, multiple GRU models with various combinations of different hyperparameters were created. The accuracies of these models were then compared to the accuracy of an ARIMA model by applying a conventional forecast accuracy test, which showed that there were significant differences in the accuracy of the models, in favor of ARIMA

What has inflammation to do with traumatic brain injury?

INTRODUCTION: Inflammation is an stereotypical response to tissue damage and has been extensively documented in experimental and clinical traumatic brain injury (TBI), including children. DISCUSSION: The initiation and orchestration of inflammation in TBI, as in other tissues, is complex and multifactorial encompassing pro- and anti-inflammatory cytokines, chemokines, adhesion molecules, complement factors, reactive oxygen and nitrogen species, and other undefined factors. It is evident that inflammation can have both beneficial and detrimental effects in TBI, but the mechanisms underlying this dichotomy are mostly unknown. Modification of the inflammatory response may be neuroprotective. Monitoring inflammation is now possible with techniques such as microdialysis; however, the prognostic value of measuring inflammatory mediators in TBI is still unclear with conflicting reports. Except for corticosteroids, no anti-inflammatory agents have been tested in TBI, and the negative results with these may have been flawed by their multiple side effects. Clinical trials with anti-inflammatory agents that target multiple or central and downstream pathways are warranted in adult and pediatric TBI. This review examines the mechanisms of inflammation after TBI, monitoring, and possible routes of intervention