The mechanisms that predispose to hypertension, coronary artery disease (CAD), and type 2 diabetes (T2D) in individuals of normal weight are poorly understood. In contrast, in monogenic primary ...lipodystrophy-a reduction in subcutaneous adipose tissue-it is clear that it is adipose dysfunction that causes severe insulin resistance (IR), hypertension, CAD, and T2D. We aimed to test the hypothesis that common alleles associated with IR also influence the wider clinical and biochemical profile of monogenic IR. We selected 19 common genetic variants associated with fasting insulin-based measures of IR. We used hierarchical clustering and results from genome-wide association studies of eight nondisease outcomes of monogenic IR to group these variants. We analyzed genetic risk scores against disease outcomes, including 12,171 T2D cases, 40,365 CAD cases, and 69,828 individuals with blood pressure measurements. Hierarchical clustering identified 11 variants associated with a metabolic profile consistent with a common, subtle form of lipodystrophy. A genetic risk score consisting of these 11 IR risk alleles was associated with higher triglycerides (β = 0.018; P = 4 × 10(-29)), lower HDL cholesterol (β = -0.020; P = 7 × 10(-37)), greater hepatic steatosis (β = 0.021; P = 3 × 10(-4)), higher alanine transaminase (β = 0.002; P = 3 × 10(-5)), lower sex-hormone-binding globulin (β = -0.010; P = 9 × 10(-13)), and lower adiponectin (β = -0.015; P = 2 × 10(-26)). The same risk alleles were associated with lower BMI (per-allele β = -0.008; P = 7 × 10(-8)) and increased visceral-to-subcutaneous adipose tissue ratio (β = -0.015; P = 6 × 10(-7)). Individuals carrying ≥17 fasting insulin-raising alleles (5.5% population) were slimmer (0.30 kg/m(2)) but at increased risk of T2D (odds ratio OR 1.46; per-allele P = 5 × 10(-13)), CAD (OR 1.12; per-allele P = 1 × 10(-5)), and increased blood pressure (systolic and diastolic blood pressure of 1.21 mmHg per-allele P = 2 × 10(-5) and 0.67 mmHg per-allele P = 2 × 10(-4), respectively) compared with individuals carrying ≤9 risk alleles (5.5% population). Our results provide genetic evidence for a link between the three diseases of the "metabolic syndrome" and point to reduced subcutaneous adiposity as a central mechanism.
Understanding the biogeochemical cycle of magnesium (Mg) is not only crucial for terrestrial ecology, as this element is a key nutrient for plants, but also for quantifying chemical weathering fluxes ...of Mg and associated atmospheric CO2 consumption, requiring distinction of biotic from abiotic contributions to Mg fluxes exported to the hydrosphere. Here, Mg isotope compositions are reported for parent basalt, bulk soils, clay fractions, exchangeable Mg, seasonal soil solutions, and vegetation for five types of volcanic soils in Iceland in order to improve the understanding of sources and processes controlling Mg supply to vegetation and export to the hydrosphere. Bulk soils (δ26Mg=−0.40±0.11‰) are isotopically similar to the parent basalt (δ26Mg=−0.31‰), whereas clay fractions (δ26Mg=−0.62±0.12‰), exchangeable Mg (δ26Mg=−0.75±0.14‰), and soil solutions (δ26Mg=−0.89±0.16‰) are all isotopically lighter than the basalt. These compositions can be explained by a combination of mixing and isotope fractionation processes on the soil exchange complex. Successive adsorption–desorption of heavy Mg isotopes leads to the preferential loss of heavy Mg from the soil profile, leaving soils with light Mg isotope compositions relative to the parent basalt. Additionally, external contributions from sea spray and organic matter decomposition result in a mixture of Mg sources on the soil exchange complex. Vegetation preferentially takes up heavy Mg from the soil exchange complex (Δ26Mgplant-exch=+0.50±0.09‰), and changes in δ26Mg in vegetation reflect changes in bioavailable Mg sources in soils. This study highlights the major role of Mg retention on the soil exchange complex amongst the factors controlling Mg isotope variations in soils and soil solutions, and demonstrates that Mg isotopes provide a valuable tool for monitoring biotic and abiotic contributions of Mg that is bioavailable for plants and is exported to the hydrosphere.
Magnesium (Mg) stable isotopes are increasingly used as a weathering proxy in soils and rivers, but the impact of the mineralogy of secondary phases on isotope fractionation remains obscure. A better ...understanding of the behaviour of Mg isotopes during weathering processes is a mandatory step toward deployment of this new tracer for understanding chemical fluxes exported from the critical zone. Here we investigate isotopic variations in δ26Mg in bulk soils and clay fractions relative to their parent andesite in three soil weathering sequences from Guadeloupe formed under contrasting climatic conditions. Soils formed in drier conditions (low precipitation) contain smectite, whereas soils formed under wet conditions (high rainfall) are characterized by halloysite and Fe-oxides or kaolinite.
All clay fractions have Mg isotopic compositions (δ26Mg −0.41‰ to −0.10‰) similar to or heavier than their parent andesite (δ26Mg −0.47‰) supporting the preferential incorporation of heavy Mg isotopes in secondary Mg-bearing clay minerals with the first direct measurements on clay fractions. Soils with lighter Mg isotope compositions have greater quantities of exchangeable Mg. The data support a contribution from sea spray to the exchangeable Mg pool correlated to the soil weathering degree. This study highlights for the first time that the soil δ26Mg not only depend on δ26Mg of the parent rock, and on any fractionation that might occur, but also on the Mg retention on the exchange complex, which could in turn be controlled by external inputs such as sea spray.
► Incorporation of heavy Mg isotopes in secondary clay minerals relative to the andesite. ► A greater amount of exchangeable Mg relates to lighter Mg isotope compositions of soils. ► Contribution from sea spray to the exchangeable Mg and the Mg isotope budget. ► Contribution to identify the processes controlling Mg isotope variations with weathering.
Techniques for the purification of Si for the determination of its natural stable isotopic composition have in the past been based on the requirements for gas-source mass-spectrometry, rather than ...MC-ICPMS. For high precision analyses by MC-ICPMS it is essential to have very pure solutions and in this paper a new technique is presented for the separation and purification of Si from natural samples to improve the determination of isotope ratios. A method has been optimised based on alkaline fusion followed by ion-exchange chromatography. The application to natural samples, such as river water samples and silicate mineral/rock samples is demonstrated. Alkali fusion avoids the use of hydrofluoric acid (HF), which introduces difficulties for the determination of Si isotope ratios using MC-ICPMS. By eliminating HF a 30–40% increase in sensitivity is achieved as well as a marked enhancement of mass bias stability leading to a factor of 2 improvement in reproducibility. The cation-exchange method enables processing of very small samples (3.6 μg Si) and a rapid and effective separation of Si from other cationic species. The overall recovery of Si during the entire procedure is better than 98% and no Si isotope fractionation is generated. Matrix tests demonstrate that this method is suitable for silicates, and that typical sulphate and nitrate abundances of river waters have no effect on measured Si isotope composition. The latter aspect is vital for analysis of river waters since the technique does not separate dissolved Si (silicic acid) from ambient anionic species. Overall, the new method presents a faster, safer and more reliable way to measure Si isotopes via MC-ICPMS.
This study presents the Si isotope compositions of the dissolved phase of twenty rivers from across Iceland. The high-resolution Nu Plasma 1700 MC-ICP-MS was used to provide interference-free
30Si/
...28Si ratios with an average limiting precision of ±
0.04‰
δ
30Si. The Si isotope composition ranges from −
0.08‰ to 1.46‰
δ
30Si, averaging 0.63
±
0.38‰ (±
1
σ
SD). This is only slightly lighter than the recently reported mean of 0.84
±
0.19‰ for high precision measurements of Swiss rivers but is significantly lighter than compositions reported for some other rivers. The Si isotope composition varies slightly with the amount of glacial cover, which provides evidence that the continental Si input to the oceans may be climatically controlled and thus likely to vary over glacial–interglacial cycles. After correction for the dissolution of trace amounts of calcite in one region, a correlation is found between
δ
30Si and Ca/Si. This is consistent with the measured basaltic composition and indicates isotopic fractionation during Si removal from the dissolved phase. By calculating the fraction of Si that is removed from the dissolved phase into secondary phases it is possible to use the riverine Si flux (Si denudation rate) to calculate the initial dissolution rate of Si within these catchments. From this study we estimate that the total amount of Si being dissolved by primary weathering of Iceland is 3 million tons per yr. However only ∼
50% of this Si is released into the rivers and contributes to denudation. Using the Si isotope composition and the Si fraction removed, it is possible to model the Si isotope fractionation as either a Rayleigh-type fractionation or a steady-state system. Both yield similar fractionation factors of about −
1.5‰
δ
30Si, implying only one underlying fractionation process that is controlled by external parameters, such as runoff. Furthermore, rivers that follow a steady-state fractionation model are associated with higher Si dissolution rates and lower
δ
30Si values, indicating an inverse relationship between weathering rates and dissolved riverine Si isotope composition.
Silicon isotope homogeneity in the mantle Savage, P.S.; Georg, R.B; Armytage, R.M.G. ...
Earth and planetary science letters,
06/2010, Letnik:
295, Številka:
1-2
Journal Article
Recenzirano
Thirty-five mafic and ultramafic rocks have been analysed for their silicon isotopic composition to very high precision with the aim of providing a robust average value for the silicate earth. This ...is of importance to studies using the difference between meteorite and terrestrial isotope composition to quantify silicon sequestration during core formation and, also, for understanding crustal processes. The δ30Si values of the samples are more limited than previously reported, ranging between just −0.39 and −0.23‰ despite significant variations in chemical and other isotopic compositions. A hint of a trend exists between δ30Si and both SiO2 and Al2O3, which can be explained by concentration of the heavier isotopes in the melt as a function of silica polymerisation. Our best estimate for the δ30Si of the bulk silicate earth (BSE) is −0.29±0.08‰ (2 s.d.).
We present hafnium (Hf) and neodymium (Nd) isotopic compositions and concentrations in surface waters of the eastern Atlantic Ocean between the coast of Spain and South-Africa. These data are ...complemented by Hf and Nd isotopic and concentration data, as well as rare earth element (REE) concentrations, in Saharan dust.
Hafnium concentrations range between a maximum of 0.52
pmol/kg in the area of the Canary Islands and a minimum value of 0.08
pmol/kg in the southern Angola Basin. Neodymium concentrations also show a local maximum in the area of the Canary Islands (26
pmol/kg) but are even higher between ∼20°N and ∼4°N reaching maximum concentrations of 35
pmol/kg. These elevated concentrations provide evidence of inputs from weathering of the Canary Islands and from the partial dissolution of dust from the Sahara/Sahel region. The inputs from ocean island weathering are also reflected in radiogenic Hf and Nd isotopes.
The Hf isotopic compositions of dust samples themselves are highly variable, ranging between
ε
Hf
=
−20 and −0.6. The combined Hf and Nd isotopic compositions of dust plot close to the “terrestrial array” during periods of appreciable dust load in the atmosphere. During low atmospheric dust loading combined Hf and Nd isotopic compositions similar to seawater are observed. Most of the variability can be explained in terms of variable degrees of zircon loss from the dust samples, which in turn is linked to sorting during atmospheric transport to the eastern Atlantic Ocean and possibly presorting by sedimentary redistribution on the continent. In addition, increasing relative proportions of radiogenic clay minerals with decreasing grain size may contribute to the radiogenic Hf isotopic compositions observed.
While the Nd isotopic composition in the surface ocean reflects the Nd isotopic composition of the Saharan dust adjacent to the Sahara/Sahel region, the release of Hf from that dust appears to be incongruent and results in surface ocean Hf isotopic compositions which are ∼10
ε
Hf more radiogenic than the bulk dust. Radiogenic Hf appears to be released from clays and possibly from trace apatite. Rare earth element patterns of dust samples indicate the presence of apatite but provide no evidence for ferromanganese grain coatings, suggesting that such coatings are insignificant in the release of Hf and Nd from Saharan dust to the surface ocean.
The Nd isotopic composition of the surface waters becomes less radiogenic south of the equator, most likely reflecting the release of Nd from Congo river sediments. The release of Hf from Saharan dust and the Congo river sediments, however, does not produce distinct Hf isotopic signatures in the surface ocean, implying that the mobile fraction of Hf integrated over large continental areas is isotopically uniform. The Hf isotopic uniformity in the surface ocean means that the limited variability in deep water isotopic compositions is consistent with a short deep water residence time and reflects homogenous continental inputs rather than efficient deep water homogenization.
Ferroptosis is a non-apoptotic form of cell death induced by small molecules in specific tumour types, and in engineered cells overexpressing oncogenic RAS. Yet, its relevance in non-transformed ...cells and tissues is unexplored and remains enigmatic. Here, we provide direct genetic evidence that the knockout of glutathione peroxidase 4 (Gpx4) causes cell death in a pathologically relevant form of ferroptosis. Using inducible Gpx4(-/-) mice, we elucidate an essential role for the glutathione/Gpx4 axis in preventing lipid-oxidation-induced acute renal failure and associated death. We furthermore systematically evaluated a library of small molecules for possible ferroptosis inhibitors, leading to the discovery of a potent spiroquinoxalinamine derivative called Liproxstatin-1, which is able to suppress ferroptosis in cells, in Gpx4(-/-) mice, and in a pre-clinical model of ischaemia/reperfusion-induced hepatic damage. In sum, we demonstrate that ferroptosis is a pervasive and dynamic form of cell death, which, when impeded, promises substantial cytoprotection.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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