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Where did we get the water? Water is essential to life on Earth, so the question of where our water came from has a certain fascination. Francis Albarède reviews evidence for the hypothesis that at the time of the giant Moon-forming impact, both the impactor and the proto-Earth were essentially dry and only much later gained volatiles by accretion of wet material delivered from beyond the asteroid belt. He concludes that the introduction of this water into Earth's mantle may have triggered plate tectonics, and that this mechanism may also have worked for the young Venus, but seems to have failed for Mars. This paper is available as part of our International Year of Astronomy package on http://go.nature.com/Z35PCw . Accretion left the terrestrial planets depleted in volatile components. Here I examine evidence for the hypothesis that the Moon and the Earth were essentially dry immediately after the formation of the Moon—by a giant impact on the proto-Earth—and only much later gained volatiles through accretion of wet material delivered from beyond the asteroid belt. This view is supported by U–Pb and I–Xe chronologies, which show that water delivery peaked ∼100 million years after the isolation of the Solar System. Introduction of water into the terrestrial mantle triggered plate tectonics, which may have been crucial for the emergence of life. This mechanism may also have worked for the young Venus, but seems to have failed for Mars.

Significance In cancer, the metabolism of copper and sulfur are dysregulated, leading to deleterious side effects. These issues are commonly addressed by studying the variations of concentrations of the elements, but here we have used, for the first time to our knowledge, copper and sulfur stable isotope compositions variations, using methods widespread in Earth sciences. We show that in hepatocellular carcinomas patients, blood copper and sulfur are enriched in light isotopes compared with control subjects. These isotopic signatures are not compatible with a dietary origin, but rather reflect the massive reallocation in the body of copper immobilized within cysteine-rich proteins such as metallothioneins. We also propose that sulfur isotope compositions could serve to track sulfur originating from tumor-derived sulfides. The widespread hypoxic conditions of the tumor microenvironment can impair the metabolism of bioessential elements such as copper and sulfur, notably by changing their redox state and, as a consequence, their ability to bind specific molecules. Because competing redox state is known to drive isotopic fractionation, we have used here the stable isotope compositions of copper ( ⁶⁵Cu/ ⁶³Cu) and sulfur ( ³⁴S/ ³²S) in the blood of patients with hepatocellular carcinoma (HCC) as a tool to explore the cancer-driven copper and sulfur imbalances. We report that copper is ⁶³Cu-enriched by ∼0.4‰ and sulfur is ³²S-enriched by ∼1.5‰ in the blood of patients compared with that of control subjects. As expected, HCC patients have more copper in red blood cells and serum compared with control subjects. However, the isotopic signature of this blood extra copper burden is not in favor of a dietary origin but rather suggests a reallocation in the body of copper bound to cysteine-rich proteins such as metallothioneins. The magnitude of the sulfur isotope effect is similar in red blood cells and serum of HCC patients, implying that sulfur fractionation is systemic. The ³²S-enrichment of sulfur in the blood of HCC patients is compatible with the notion that sulfur partly originates from tumor-derived sulfides. The measurement of natural variations of stable isotope compositions, using techniques developed in the field of Earth sciences, can provide new means to detect and quantify cancer metabolic changes and provide insights into underlying mechanisms.

Interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) are both monocyte-derived cytokines. Both cytokines have been previously described to exert a role in rheumatoid arthritis (RA) pathogenesis synergizing with other pro-inflammatory mediators, such as interleukin-17 (IL-17) on target cells, for the perpetuation of the inflammatory response (e.g. IL-6 production). In the context of experimental RA, Cd addition has an anti-proliferative and anti-inflammatory effect when associated to IL-17/TNF-α stimulation, due to its accumulation in synoviocytes. The aim of this work was to evaluate if IL-1β interaction with IL-17 also contributes to metal-import mechanisms and its effects on cell viability and inflammation. IL-17 and IL-1β were added to synoviocyte cultures with or without exogenous Cd addition (0.1 ppm, 0.89 μM). IL-6 production, Cd import kinetics, gene expression of ZIP-8 importer and metallothioneins (MTs) and cell viability were evaluated by ELISA, inductively-coupled mass spectrometry (ICP-MS), q-RT-PCR and viability assays (neutral red and annexin V) respectively. IL-17 and IL-1β acted in synergy on synoviocytes to induce IL-6 production similarly to the IL-17/TNF-α combination. Metal import was lower with IL17/ IL-1β in comparison to IL-17/TNF-α exposed-synoviocytes, as the expression of ZIP-8 and MT-1F was less induced. Monocyte and PBMCs exposure to Cd resulted in a reduced production of IL-1β and an increased production of TNF-α and this result was confirmed in co-cultures of synoviocytes and PBMCs. The IL-17/IL-1β combination with Cd slightly reduced cell viability in comparison to the IL-17/TNF-α combination and resulted in a strong induction of IL-6 production. IL-17/TNF-α combination but not IL-17/IL-1β combination mainly drives the accumulation of Cd in synoviocytes and its effects on cell viability and inflammation.

Stable Zn isotopes are fractionated in roots and leaves of plants. Analyses demonstrate that the heavy Zn isotopes are enriched in the root system of plants with respect to shoots and leaves as well as the host soil, but the fractionation mechanisms remain unclear. Here we show that the origin of this isotope fractionation is due to a chemical isotope effect upon complexation by Zn malates and citrates in the aerial parts and by phosphates in the roots. We calculated the Zn isotope effect in aqueous citrates, malates, and phosphates by ab initio methods. For pH<5, the Zn isotopic compositions of the various parts of the plants are expected to be similar to those of groundwater. In the neutral to alkaline region, the calculations correctly predict that (66)Zn is enriched over (64)Zn in roots, which concentrate phosphates, with respect to leaves, which concentrate malates and citrates, by about one permil. It is proposed that Zn isotope fractionation represents a useful tracer of Zn availability and mobility in soils.

It is now universally accepted that utilization of lead for domestic purposes and water distribution presents a major health hazard. The ancient Roman world was unaware of these risks. How far the gigantic network of lead pipes used in ancient Rome compromised public health in the city is unknown. Lead isotopes in sediments from the harbor of Imperial Rome register the presence of a strong anthropogenic component during the beginning of the Common Era and the Early Middle Ages. They demonstrate that the lead pipes of the water distribution system increased Pb contents in drinking water of the capital city by up to two orders of magnitude over the natural background. The Pb isotope record shows that the discontinuities in the pollution of the Tiber by lead are intimately entwined with the major issues affecting Late Antique Rome and its water distribution system.

The redox state of arc mantle The redox state of the upper mantle beneath arcs is relevant to understanding mantle melting and melt differentiation. Because we have no access to samples from the convective mantle, this question has to be addressed indirectly using information derived from the chemistry of melts. Cin-Ty Lee et al . show that the ratio of zinc to total iron content constrains the valence state of iron in primary arc basalts and their mantle sources. They find that primitive arc magmas have Zn/Fe ratios identical to those of mid-ocean ridge basalts, hinting at a similar iron oxidation state of primary mantle melts in arcs and ridges. The results suggest that the subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. They conclude that the observed higher oxidation states of arc lavas must therefore be, in part, a consequence of shallow-level differentiation processes. Here it is shown that the ratio of zinc to total iron content constrains the valence state of iron in primary arc basalts and their mantle sources. Primitive arc magmas have identical Zn/Fe T ratios (Fe T = Fe 2+ + Fe 3+ ) as mid-ocean-ridge basalts, indicating a similar iron oxidation state of primary mantle melts in arcs and ridges and that the subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. It is concluded that the observed higher oxidation states of arc lavas must therefore be, in part, a consequence of shallow-level differentiation processes. Many arc lavas are more oxidized than mid-ocean-ridge basalts and subduction introduces oxidized components into the mantle 1 , 2 , 3 , 4 . As a consequence, the sub-arc mantle wedge is widely believed to be oxidized 3 , 5 . The Fe oxidation state of sub-arc mantle is, however, difficult to determine directly, and debate persists as to whether this oxidation is intrinsic to the mantle source 6 , 7 . Here we show that Zn/Fe T (where Fe T = Fe 2+  + Fe 3+ ) is redox-sensitive and retains a memory of the valence state of Fe in primary arc basalts and their mantle sources. During melting of mantle peridotite, Fe 2+ and Zn behave similarly, but because Fe 3+ is more incompatible than Fe 2+ , melts generated in oxidized environments have low Zn/Fe T . Primitive arc magmas have identical Zn/Fe T to mid-ocean-ridge basalts, suggesting that primary mantle melts in arcs and ridges have similar Fe oxidation states. The constancy of Zn/Fe T during early differentiation involving olivine requires that Fe 3+ /Fe T remains low in the magma. Only after progressive fractionation does Fe 3+ /Fe T increase and stabilize magnetite as a fractionating phase. These results suggest that subduction of oxidized crustal material may not significantly alter the redox state of the mantle wedge. Thus, the higher oxidation states of arc lavas must be in part a consequence of shallow-level differentiation processes, though such processes remain poorly understood.

Estimating global fluxes of precious metals is key to understanding early monetary systems. This work adds silver (Ag) to the metals (Pb and Cu) used so far to trace the provenance of coinage through variations in isotopic abundances. Silver, copper, and lead isotopes were measured in 91 coins from the East Mediterranean Antiquity and Roman world, medieval western Europe, 16th-18th century Spain, Mexico, and the Andes and show a great potential for provenance studies. Pre-1492 European silver can be distinguished from Mexican and Andean metal. European silver dominated Spanish coinage until Philip III, but had, 80 y later after the reign of Philip V, been flushed from the monetary mass and replaced by Mexican silver.

Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike 70Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-α). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. Exposure to IL-17 and TNF-α enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations.

Copper isotopic composition is altered in cancerous compared to healthy tissues. However, the rationale for this difference is yet unknown. As a model of Cu isotopic fractionation, we monitored Cu uptake in Saccharomyces cerevisiae , whose Cu import is similar to human. Wild type cells are enriched in 63 Cu relative to 65 Cu. Likewise, 63 Cu isotope enrichment in cells without high-affinity Cu transporters is of slightly lower magnitude. In cells with compromised Cu reductase activity, however, no isotope fractionation is observed and when Cu is provided solely in reduced form for this strain, copper is enriched in 63 Cu like in the case of the wild type. Our results demonstrate that Cu isotope fractionation is generated by membrane importers and that its amplitude is modulated by Cu reduction. Based on ab initio calculations, we propose that the fractionation may be due to Cu binding with sulfur-rich amino acids: methionine and cysteine. In hepatocellular carcinoma (HCC), lower expression of the STEAP3 copper reductase and heavy Cu isotope enrichment have been reported for the tumor mass, relative to the surrounding tissue. Our study suggests that copper isotope fractionation observed in HCC could be due to lower reductase activity in the tumor.

Zinc (Zn) has major effects on immune system activation while Cadmium (Cd) has anti-inflammatory and anti-proliferative effects in several chronic inflammatory contexts. The aim of this work was to investigate by which mechanisms Zn could compete with Cd and eventually counteract its deleterious effects. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation; osteoarthritis (OA) synoviocytes were used as control. Cell/medium fractionation constants were analyzed for different metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn spike. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1 (MT-1s) and the ratio between metalloprotease-3 and the tissue inhibitor of metalloproteinases (MMP-3)/TIMP-1) were evaluated after pre-exposure to cytokines and Cd, with or without the addition of exogenous Zn (0.9 ppm). Cell viability was measured by neutral red assay and IL-6 production by ELISA. Synoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal import increased with IL-17/TNF-α exposure, through the enhanced ZIP-8 expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05). Zn induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3-fold), and subsequently the final intra-cellular content of Cd. By reducing Cd accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was enhanced by inflammatory conditions. Zinc counteracts the deleterious effect of Cd by reducing its import and accumulation in the cell, without the reactivation of destructive pathways such as MMPs.