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HSP90 are abundant molecular chaperones, assisting the folding of several hundred client proteins, including substrates involved in tumor growth or neurodegenerative diseases. A complex set of large ATP-driven structural changes occurs during HSP90 functional cycle. However, the existence of such structural rearrangements in apo HSP90 has remained unclear. Here, we identify a metastable excited state in the isolated human HSP90α ATP binding domain. We use solution NMR and mutagenesis to characterize structures of both ground and excited states. We demonstrate that in solution the HSP90α ATP binding domain transiently samples a functionally relevant ATP-lid closed state, distant by more than 30 Å from the ground state. NMR relaxation enables to derive information on the kinetics and thermodynamics of this interconversion, while molecular dynamics simulations establish that the ATP-lid in closed conformation is a metastable exited state. The precise description of the dynamics and structures sampled by human HSP90α ATP binding domain provides information for the future design of new therapeutic ligands. To refold client proteins, HSP90 chaperone undergoes large structural rearrangements. Here the authors use NMR and molecular simulation and reveal structure and dynamics of a key functionally relevant metastable state of human HSP90α N-terminal domain.

Located in the South-West Pacific, at the northern extremity of the mostly submerged Zealandia continent, the New Caledonian Exclusive Economic Zone (EEZ) covers 1,470,000 km² and includes basins, ridges and seamounts where abundant ferromanganese crusts have been observed. Several investigations have been conducted since the 1970s on the nature and composition of ferromanganese crusts from New Caledonia’s seamounts and ridges, but none have covered the entire EEZ. We present data from 104 ferromanganese crusts collected in New Caledonia’s EEZ during twelve oceanographic cruises between 1974 and 2019. Samples were analysed for mineralogy, geochemical compositions, growth rates, and through a statistical approach using correlation coefficients and factor analysis. Crust thicknesses range from 1 mm to 115 mm, with growth rates between 0.45 mm/Ma and 102 mm/Ma. Based on textures, structures, discrimination plots, and growth rates, we distinguish a group of hydrogenetic crusts containing the highest mean contents of Co (0.42 wt%), Ni (0.31 wt%), and high contents of Mo, V, W, Pb, Zn, Nb, from a group of hydrothermal and/or diagenetic deposits showing high mean contents of Mn (38.17 wt%), Ba (0.56 wt%) and low contents of other trace metals. Several samples from this later group have exceptionally high content of Ni (0.7 wt%). The data shows that crusts from the southern part of the EEZ, notably seamounts of the Loyalty Ridge and the Lord Howe Rise, present high mineral potential for prospectivity owing to high contents of valuable metals, and constitute a great target for further investigation.

The perceived supply risk for essential materials used in the development of green energy and other state-of-the art technologies creates the need for investigation of new sources for these raw materials. Many of these raw materials are characterized as “critical” given supply risks posed by geographic location, the economic and political stability of producing countries, potential substitution and opportunities for recycling [European Commission, 2014]. At present, 20 raw materials are listed by the EU as critical and this inventory is likely to grow in the coming years as the world population increases, driven by the development of India, China, Africa, Brazil and others. Among these critical elements, the rare earth elements and yttrium (REY) form a group of 15 metals essential for the development of wind turbines, cell phones and batteries among other applications and their production has been under Chinese domination for the last three decades. More than 95 % of the consumed REY worldwide originated in China during the last thirty years, a monopole that reflects economical constrains rather than the unequal distribution of REY resources across the world. Indeed, important proven reserves are known outside China though their extraction is expensive and energy consuming. In addition, most REY-rich deposits possess important concentrations of actinides (U and Th) problematic for waste disposal. This study therefore investigates the potential recovery of REY from umbers, metalliferous sediments of the Troodos massif in Cyprus, as an alternative to the dominant magmatic-related REY deposits. Field evidence and geochemical characterisation of umbers show strong similarities with high-temperature plume fall-out deposits observed in most mid-oceanic ridge settings. Umbers constitute fine-grained brown Fe-Mn-rich mudstones with an amorphous oxyhydroxides dominated mineralogy and total rare earth oxide contents of ≈0.05 wt. %. REY fractionation trends show excellent comparison with signatures of hydrothermal particles settling around active vents. The umbers display a negative Ce anomaly in a convex upward REE trend when normalized to chondrite, characteristic of a hydrothermal signal overprinted by seawater. From an economic perspective, although the REE content is low, the absence of mineralogical control on the distribution of these elements in umbers and the extremely low radioactive content (Th + U < 5 ppm) makes their potential extraction attractive. A protocol for the leaching of umbers is presented testing a variety of lixiviants used in the REY extractive industry. Results show a strong mobilisation of the lanthanides in the solution in comparison with non-targeted elements. Most importantly, the results presented highlight that 80 to 90 % of the initial REY content of umbers is leached out using weak acid concentration in a matter of hours at low temperature. Fractionation along the REY series during leaching usually favours the release of the middle and light REE with a decreasing trend towards the heavy REE, except for Yttrium. Ce recovery is minimal as a result of its tetravalent oxidation state allowing formation of acid-resistant Ce oxides. Furthermore, a process of selective precipitation is presented for the purification of the leach solution and extraction of a solid REY phase using ammonium oxalate as a complexing and chelating agent. Precipitation experiments show the precipitation efficiency is a function of pH, between pH values ranging from 0.7 to 3.2, with more than 96 % of REY precipitated at pH > 1.1. Purity of the precipitate is adjusted using precise pH buffering to avoid Ca-oxalate formation as the major impurity. Indeed, mass balance calculations and direct EDS measurement of the oxalate precipitate by SEM show maximal purity at pH 1.1 (66 – 94 % REY) while increasing Ca precipitation decrease purity below 10 % at pH > 1.5. The fractionation observed along the lanthanide series during the precipitation experiments was successfully reproduced via numerical modelling using PHREEQC software. REE distribution within the precipitate therefore reflects the interplay of aqueous and solid REY-oxalate complexes stability constants as well as incorporation of REY within the structure of co-precipitating Ca- and Na-oxalates. This study demonstrates the feasibility of extracting efficiently REY from Fe-Mn oxide-rich metalliferous sediments. These deposits constitute interesting alternatives to high-grade deposits and their processing for REY production could be valuated as a by-product of pigment production. Alternatively, the process presented here could be applied to other oxide-based formations including marine ferromanganese deposits, or industrial wastes containing comparable high-tech metals concentration and enrichment process.

The decarbonisation of our energy supply is reliant on new technologies that are raw material intensive and will require a significant increase in the production of metals to sustain them. Ferromanganese (FeMn) crusts are seafloor precipitates, enriched in metals such as cobalt and tellurium, both of which have a predicted future demand above current production rates. In this study, we investigate the texture and composition of FeMn crusts on Tropic Seamount, a typical Atlantic guyot off the coast of western Africa, as a basis for assessing the future mineral resource potential of Atlantic Seamounts. The majority of the summit is flat and covered by FeMn crusts with average thicknesses of 3–4 cm. The crusts are characterized by two dominant textures consisting of either massive pillared growth or more chaotic, cuspate sections of FeMn oxides, with an increased proportion of detrital and organic material. The Fe, Mn, and Co contents in the FeMn oxide layers are not affected by texture. However, detrital material and bioclasts can form about 50% of cuspate areas, and the dilution effect of this entrained material considerably reduces the Fe, Mn, and Co concentrations if the bulk samples are analyzed. Whilst Tropic Seamount meets many of the prerequisites for a crust mining area, the thickness of the crusts and their average metal composition means extraction is unlikely to be viable in the near future. The ability to exploit more difficult terrains or multiple, closely spaced edifices would make economic feasibility more likely.

An investigation of the corrosion processes were performed for coated and uncoated ?-TiAl G4, an alloy designed to work in the temperature range 750-800°C, where oxidation and corrosion phenomena occur. An aluminising pack cementation treatment was used to improve the oxidation resistance of this ?-TiAl G4 alloy. Cyclic corrosion tests were performed at 800°C in air for up to 800 1-hour cycles with a Na2SO4/NaCl mixture. The influence of both aluminisation and the corrosion phenomena on the creep behaviour was investigated. The cyclic corrosion resistance of the coated g TiAl G4 was shown to be improved by aluminising. The pack cementation treatment had no detrimental effect on the creep behaviour. Moreover, neither is creep affected by the corrosion of coated specimens. As corroded uncoated specimen exhibited good creep behaviour, it can be concluded that this alloy is suitable, even without coating, for turbine applications in hot corrosion atmospheres at least up to 800°C.

An investigation of the corrosion processes were performed for coated and uncoated γ-TiAl G4, an alloy designed to work in the temperature range 750 - 800°C, where oxidation and corrosion phenomena occur. An aluminising pack cementation treatment was used to improve the oxidation resistance of this γ-TiAl G4 alloy. Cyclic corrosion tests were performed at 800°C in air for up to 800 1-hour cycles with a Na 2 SO 4 /NaCl mixture. The influence of both aluminisation and the corrosion phenomena on the creep behaviour was investigated. The cyclic corrosion resistance of the coated γ- TiAl G4 was shown to be improved by aluminising. The pack cementation treatment had no detrimental effect on the creep behaviour. Moreover, neither is creep affected by the corrosion of coated specimens. As corroded uncoated specimen exhibited good creep behaviour, it can be concluded that this alloy is suitable, even without coating, for turbine applications in hot corrosion atmospheres at least up to 800°C.

HSP90 are abundant molecular chaperones, assisting the folding of several hundred client proteins, including substrates involved in tumor growth or neurodegenerative diseases. A complex set of large ATP-driven structural changes occurs during HSP90 functional cycle. However, the existence of such structural rearrangements in apo HSP90 has remained unclear. Here, we identified a metastable excited state in the isolated HSP90 ATP binding domain. We used solution NMR and mutagenesis to characterize structures of both ground and excited states. We demonstrated that in solution the HSP90 ATP binding domain transiently samples a functionally relevant ATP-lid closed state, distant by more than 30 Å from the ground state. NMR relaxation and molecular dynamics were combined to characterize the energy landscape corresponding to the transition between these interconverting states. The precise description of the dynamics and structures sampled by human HSP90 ATP binding domain is a paramount piece of information for the future design of new therapeutic ligands. Competing Interest Statement The authors have declared no competing interest.

A collaborative study, supported by the Biomed2 Programme of the European Community, was initiated to optimise the aetiological diagnosis in genetic or gonadal males with intersex disorders, a total of 67 patients with external sexual ambiguity, testicular tissue and/or a XY karyotype. In patients with gonadal dysgenesis or true hermaphroditism, the incidence of vaginal development was 100%, a uterus was present in 60%; uni or bilateral cryptorchidism was seen in nearly all cases of testicular dysgenesis (99%) but in only 57% of true hermaphrodites. Mean serum levels of anti-mullerian hormone and of serum testosterone response to chorionic gonadotropin stimulation were significantly decreased in both conditions, by comparison with patients with unexplained male pseudohermaphroditism or partial androgen insensitivity (PAIS). Mutations in the androgen receptor, 90% within exons 2-8, were detected in patients with PAIS. Clinically, a vaginal pouch was present in 90%, cryptorchidism in 36%. In 52% of cases, no diagnosis could be reached, despite an exhaustive clinical and laboratory work-up, including routine sequencing of exons 2-8 of the androgen receptor. By comparison with PAIS, unexplained male pseudohermaphroditism was characterised by a lower incidence of vaginal pouch (55%) and cryptorchidism (22%) but a high incidence of prematurity/intrauterine growth retardation (30%) or mild malformations (14%). reaching an aetiological diagnosis in cases of male intersex is difficult because of the variability of individual cases. Hormonal tests may help to discriminate between partial androgen insensitivity and gonadal dysgenesis/true hermaphroditism but are of less use for differentiating from unexplained male pseudohermaphroditism. Sequencing of exons 2-8 of the androgen receptor after study of testosterone precursors following human chorionic gonadotrophin stimulation is recommended when gonadal dysgenesis and true hermaphroditism can be excluded.