Saltwater Intrusion Modifies Microbial Community Structure and Decreases Denitrification in Tidal Freshwater Marshes

Environmental changes can alter the interactions between biotic and abiotic ecosystem components in tidal wetlands and therefore impact important ecosystem functions. The objective of this study was to determine how saltwater intrusion affects wetland nutrient biogeochemistry, with a specific focus on the soil microbial communities and physicochemical parameters that control nitrate removal. Our work took place in a tidal freshwater marsh in South Carolina, USA, where a 3.5-year saltwater intrusion experiment increased porewater salinities from freshwater to oligohaline levels. We measured rates of denitrification, soil oxygen demand, and dissimilatory nitrate reduction to ammonium (DNRA) and used molecular genetic techniques to assess the abundance and community structure of soil microbes. In soils exposed to elevated salinities, rates of denitrification were reduced by about 70% due to changes in the soil physicochemical environment (higher salinity, higher carbon:nitrogen ratio) and shifts in the community composition of denitrifiers. Saltwater intrusion also affected the microbial community responsible for DNRA, increasing the abundance of genes associated with this process and shifting microbial community composition. Though rates of DNRA were below detection, the microbial community response may be a precursor to increased rates of DNRA with continued saltwater intrusion. Overall, saltwater intrusion reduces the ability of tidal freshwater marshes to convert reactive nitrogen to dinitrogen gas and therefore negatively affects their water quality functions. Continued study of the interrelationships between biotic communities, the abiotic environment, and biogeochemical transformations will lead to a better understanding of how the progressive replacement of tidal freshwater marshes with brackish analogues will affect the overall functioning of the coastal landscape

Global sensitivity analysis of stochastic computer models with joint metamodels

The global sensitivity analysis method used to quantify the influence of uncertain input variables on the variability in numerical model responses has already been applied to deterministic computer codes; deterministic means here that the same set of input variables gives always the same output value. This paper proposes a global sensitivity analysis methodology for stochastic computer codes, for which the result of each code run is itself random. The framework of the joint modeling of the mean and dispersion of heteroscedastic data is used. To deal with the complexity of computer experiment outputs, nonparametric joint models are discussed and a new Gaussian process-based joint model is proposed. The relevance of these models is analyzed based upon two case studies. Results show that the joint modeling approach yields accurate sensitivity index estimatiors even when heteroscedasticity is strong

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe

Clustering Variable Length Sequences by Eigenvector Decomposition Using HMM

We present a novel clustering method using HMM parameter space and eigenvector decomposition. Unlike the existing methods, our algorithm can cluster both constant and variable length sequences without requiring normalization of data. We show that the number of clusters governs the number of eigenvectors used to span the feature similarity space. We are thus able to automatically compute the optimal number of clusters. We successfully show that the proposed method accurately clusters variable length sequences for various scenarios