Targeted next generation sequencing approach identifies eighteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome

The genetic basis is unknown for ∼60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 18 new candidate genes including: AMN1, CCKBR, CRY1, CXCR4, FGF13, GAP43, GLI3, JAG1, NOS1, MASTL, NOTCH1, NRP2, PALM2, PDE3A, PLEKHA5, RD3, and TRAPPC9, and TSPAN11. Digenic and trigenic variants were found in 8/48 (16.7%) and 1/48 (2.1%) patients, respectively. NGS with confirmation by Sanger sequencing resulted in the identification of new causative FGFR1 gene mutations and suggested 18 new candidate genes in nHH/KS

Statistical sampling design impact on predictive quality of harmonization functions between soil monitoring networks

Regulations about soil quality are normally imposed at international level while many countries have set up monitoring networks at national scale. Since these networks use different sampling strategies, there is a strong need to harmonize a posteriori the collected data from the national networks in order to answer questions raised by the global regulations. For that purpose, calibration sites where different sampling strategies are carried out are necessary in order to construct harmonization functions between measurements from different sampling protocols. A case study is available for French forest soils that have been sampled twice simultaneously on the same sampling grid but with different sampling and analytical strategies: a first sampling for the French soil quality monitoring network (RMQS) and a second one for the European forest monitoring network (ICP Forests level I second survey i.e. Biosoil). However, the way to define the number and the position of these calibration sites remains a key issue. In this work, we compare both RMQS and Biosoil strategies for a set of measured variables of interest (carbon, potassium and lead contents and pH) and aim to define the minimum number of sites and their best location to establish reliable harmonization functions. Three statistical methods for construction of sampling designs are tested: random sampling, conditioned Latin Hypercube Sampling (cLHS, Minasny and McBratney, 2006) and D-Latin Hypercube Sampling (DLHS, Minasny and McBratney, 2010). With each method, we investigate the effects of the number of calibration data on the predictive quality of the harmonization functions. First, we show that both cLHS and DLHS are better than simple random sampling. Then, the difference between cLHS and DLHS performance depends mainly on the size of the samples, the nature of the soil property and the form of the pedotransfer functions. (C) 2013 Elsevier B.V. All rights reserved

Nickel distribution and isotopic fractionation in a Brazilian lateritic regolith: coupling Ni isotopes and Ni K-edge XANES.

Ultramafic (UM) rocks are known to be nickel (Ni) rich and to weather quickly, which makes them a good candidate to look at the Ni isotope systematics during weathering processes at the Earth’s surface. The present study aims at identifying the Ni solid speciation and discussing the weathering processes that produce Ni isotope fractionation in two deep laterite profiles under tropical conditions (Barro Alto, Goiás State, Brazil). While phyllosilicates and to a lower extent goethite are the main Ni-bearing phases in the saprolitic part of the profile, iron (Fe) oxides dominate the Ni budget in the lateritic unit. Nickel isotopic composition (δ60Ni values) has been measured in each unit of the regolith, i.e., rock, saprock, saprolite and laterite (n=52). δ60Ni varies widely within the two laterite profiles, from -0.10 ± 0.05‰ to 1.43 ± 0.05‰, showing that significant Ni isotope fractionation occurs during the weathering of UM rocks. Overall, our results show that during weathering, the solid phase is depleted in heavy Ni isotopes due to the preferential sorption and incorporation of light Ni isotopes into Fe oxides; the same mechanisms likely apply to the incorporation of Ni into phyllosilicates (type 2:1). However, an isotopically heavy Ni pool is observed in the solid phase at the bottom of the saprolitic unit. This feature can be explained by two hypotheses that are not mutually exclusive: i) a depletion in light Ni isotopes during the first stage of weathering due to the preferential dissolution of light Ni-containing minerals, and ii) the sorption or incorporation of isotopically heavy Ni carried by percolating waters (groundwater samples have δ60Ni of 2.20 and 2.27‰), that were enriched in heavy Ni isotopes due to successive weathering processes in the overlying soil and laterite units

Nickel isotope fractionation during laterite Ni ore smelting and refining: implications for tracing the sources of Ni in smelter-affected soils

Nickel isotope ratios were measured in ores, fly ash, slags and FeNi samples from two metallurgical plants located in the Goiás State, Brazil (Barro Alto, Niquelândia). This allowed investigating the mass-dependent fractionation of Ni isotopes during the Ni-laterite ore smelting and refining. Feeding material exhibits a large range of δ60Ni values (from 0.02 ± 0.10 ‰ to 0.20 ± 0.05 ‰, n=7), explained by the diversity of Ni-bearing phases, and the average of δ60Nifeeding materials was found equal to 0.08 ± 0.08‰ (2SD, n=7). Both δ60Ni values of fly ash (δ60Ni = 0.07 ± 0.07‰, n=10) and final FeNi produced (0.05 ± 0.02 ‰, n=2) were not significantly different from the feeding materials ones. These values are consistent with the very high production yield of the factories. However, smelting slags present the heaviest δ60Ni values of all the smelter samples, with δ60Ni ranging from 0.11 ± 0.05 ‰ to 0.27 ± 0.05 ‰ (n=8). Soils were also collected near and far from the Niquelândia metallurgical plant, to evaluate the potential of Ni isotopes for tracing the natural vs anthropogenic Ni in soils. The Ni isotopic composition of the non-impacted topsoils developed on ultramafic rocks ranges from -0.26 ± 0.09 ‰ to -0.04 ± 0.05 ‰ (n=20). On the contrary, the Ni isotopic composition of the non-ultramafic topsoils, collected close to the plant, exhibit a large variation of δ60Ni, ranging from -0.19 ± 0.13 ‰ up to 0.10 ± 0.05 ‰ (n=4). This slight but significant enrichment in heavy isotopes highlight the potential impact of smelting activity in the surrounding area, as well as the potential of Ni isotopes for discerning anthropogenic samples (heavier δ60Ni values) from natural ones (lighter δ60Ni values). However, given the global range of published δ60Ni values (from -1.03 to 2.5 ‰) and more particularly those associated to natural weathering of ultramafic rocks (from -0.61 to 0.32‰), the use of Ni isotopes for tracing environmental contamination from smelters will remain challenging

Nickel isotope fractionation during tropical weathering of ultramafic rocks

Although Ni isotopes have been shown to be significantly fractionated in terrestrial samples, their use in continental environmental studies has not yet been evaluated. The present study focuses on an ultramafic (UM) massif (Barro Alto, Goias, Brazil) because such areas are naturally rich in Ni. We present developed lateritic weathering profiles. The goal of the study is to evaluate the potential of using Ni isotopes in environmental continental studies by combining its isotopic signature with mineralogy, in order to better understand the geochemical cycling of Ni in UM settings during weathering. As such, Ni isotope values were measured in samples from the Barro Alto UM complex in the main stages of the lateritic weathering profile of UM rocks, including bedrock, ores (saprolitic and lateritic samples) and soil. The mineralogical composition of the samples, with a focus on the different Ni-bearing minerals, was also determined to decipher the potential links between isotopic fractionation and weathering dynamics. Isotopic signatures (δ60Ni) from the natural Ni geochemical cycle include: bedrock samples (δ60Ni = 0.28 ± 0.08‰), ore samples (saprolitic and lateritic, δ60Ni from -0.60 to 0.30‰) and soil samples (δ60Ni from -0.19 to -0.02‰). An overall trend of heavier isotope depletion was observed in the solid phase during weathering (Δ60NiSoil-Bedrock = -0.47‰). The mineralogical results were consistent with the literature and showed that the mineralogy of the lateritic part and soil was dominated by Fe-oxides, whereas clay minerals were the primary Ni phase scavengers in the saprolitic part of the profile. Thus, the formation of Ni-bearing clay minerals and Fe-oxides appeared to lead to depletion in heavier isotopes, which indicates preferential export of heavy isotopes in the dissolved phase. This result is consistent with isotopic signatures measured in the exchangeable pool of the solid phase (Δ60Niexch-total up to 0.47‰), and Ni isotopes appear to be a promising tracer to better understand the biogeochemical Ni cycling on the Earth’s surface

Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe´s terrestrial ecosystems: a review

Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributedobservation programmes designed to monitor climatechange, better understand its impacts on global ecosystems,and evaluate possible mitigation and adaptation strategies. Thepan-European Integrated Carbon Observation System combinescarbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observationswithin the atmosphere, terrestrial ecosystems and oceans.High-precision measurements are obtained using standardisedmethodologies, are centrally processed and openly available ina traceable and verifiable fashion in combination with detailedmetadata. The Integrated Carbon Observation System ecosystemstation network aims to sample climate and land-cover variabilityacross Europe. In addition to GHG flux measurements,a large set of complementary data (including management practices,vegetation and soil characteristics) is collected to supportthe interpretation, spatial upscaling and modelling of observedecosystem carbon and GHG dynamics. The applied samplingdesign was developed and formulated in protocols by the scientificcommunity, representing a trade-off between an ideal datasetand practical feasibility. The use of open-access, high-quality andmulti-level data products by different user communities is crucialfor the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.<br