BackgroundThe mechanisms of toxicity of metal oxide particles towards lung cells are far from being understood. In particular, the relative contribution of intracellular particulate versus solubilized fractions is rarely considered as it is very challenging to assess, especially for low-solubility particles such as cobalt oxide (Co3O4).MethodsThis study was possible owing to two highly sensitive, independent, analytical techniques, based on single-cell analysis, using ion beam microanalysis, and on bulk analysis of cell lysates, using mass spectrometry.ResultsOur study shows that cobalt oxide particles, of very low solubility in the culture medium, are readily incorporated by BEAS-2B human lung cells through endocytosis via the clathrin-dependent pathway. They are partially solubilized at low pH within lysosomes, leading to cobalt ions release. Solubilized cobalt was detected within the cytoplasm and the nucleus. As expected from these low-solubility particles, the intracellular solubilized cobalt content is small compared with the intracellular particulate cobalt content, in the parts-per-thousand range or below. However, we were able to demonstrate that this minute fraction of intracellular solubilized cobalt is responsible for the overall toxicity.ConclusionsCobalt oxide particles are readily internalized by pulmonary cells via the endo-lysosomal pathway and can lead, through a Trojan-horse mechanism, to intracellular release of toxic metal ions over long periods of time, involving specific toxicity.

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[1] The Amsterdam-Saint Paul plateau results from a 10 Myr interaction between the South East Indian Ridge and the Amsterdam-Saint Paul hot spot. During this period of time, the structure of the plateau changed as a consequence of changes in both the ridge-hot spot relative distance and in the strength of the hot spot source. The joint analysis of gravity-derived crust thickness and bathymetry reveals that the plateau started to form at ∼10 Ma by an increase of the crustal production at the ridge axis, due to the nearby hot spot. This phase, which lasted 3-4 Myr, corresponds to a period of a strong hot spot source, maybe due to a high temperature or material flux, and decreasing ridge-hot spot distance. A second phase, between ∼6 and ∼3 Ma, corresponds to a decrease in the ridge crustal production. During this period, the hot spot center was close to the ridge axis and this reduced magmatic activity suggests a weak hot spot source. At ∼3 Ma, the ridge was located approximately above the hot spot center. An increase in the hot spot source strength then resulted in the building of the shallower part of the plateau. The variations of the melt production at the ridge axis through time resulted in variations in crustal thickness but also in changes in the ridge morphology. The two periods of increased melt production correspond to smooth ridge morphology, characterized by axial highs, while the intermediate period corresponds to a rougher, rift-valley morphology. These variations reveal changes in axial thermal structure due to higher melting production rates and temperatures.

[1] The Amsterdam-St. Paul (ASP) plateau is located in the central part of the Indian Ocean and results from the interaction between the ASP hot spot and the Southeast Indian Ridge (SEIR). It is located near the diffuse boundary between the Capricorn and Australian plates. The seamount chain of the Dead Poets (CDP) is northeast of the ASP plateau and may represent older volcanism related to the ASP hot spot; this chain consists of two groups of seamounts: (1) large flat-topped seamounts formed 8-10 Ma and (2) smaller conical seamounts formed during the last 2 Myr. The ASP hot spot has produced two pulses of magmatism that have been ponded under the ASP plateau and erupted along the divergent boundary between the Capricorn and Australian plates. The N65°orientation of the CDP as well as the seamount's elongated shapes support an opening motion between the Capricorn and Australian plates along a suture oriented in the N155°direction. This motion compared to the Antarctic plate amounts to an apparent velocity of 7.7 cm/yr northeastward for the Capricorn-Australian block. This motion does not fit with a fixed plume model. We suggest, therefore, that the ASP plume experienced a motion of about 1-2 cm/yr to the SW, which is opposite to the asthenospheric flow in this region and suggests a deep-seated plume.

In a context of convergence between Africa and Europe, the western Mediterranean domain is characterized by the opening of the Liguro-Provençal ocean in the early Miocene and of the Tyrrhenian Sea since the middle Miocene. These openings are preceded by an Oligocene rifting episod. New biostratigraphic, geochronologic and paleomagnetic data allow to propose an integrated stratigraphy sketch for the Oligo-Miocene period in Corsica. The continental syn-rift deposits, in the region of Ajaccio, have been dated as late Chattian from the presence of a mammal, Pomelomeryx boulangeri. Their paleomagnetic study indicates an anticlockwise rotation of 44 ±4° with regard to the stable Europe. The early Miocene succession was deposited on a contrasted topography inherited from the Oligocene glyptogenesis period. The lowermost Miocene deposits are represented by 4 pyroclastic flow deposits in southern Corsica. New 40Ar-39Ar datings on plagioclase concentrates give ages between 21.3 and 20.6 Ma (late Aquitanian). Paleomagnetic directions indicates that the rotation of Corsica had probably begun at this time. The Miocene marine sediments of the Bonifacio basin are divided in two formations. At the base, the Cala di Labra formation, that comprises 3 reef formations in coastal onlap (R1, R2, R3), is attributable to the Globigerinoides trilobus zone. In the environment of R1, miogypsin population includes mainly Miogypsina intermedia with a few M. globulina and M. cushmani. The absence of the less evolved forms (10 < V < 35) let us suppose that at least the lower Burdigalian is absent at Bonifacio because the region was emerged. R2 reef has a similar population (42 < V < 70), which suggests a rather short interval of time between the two stages of reef construction. On the other hand the R3 population contains only evolved forms (M. mediterranea) suggesting a late Burdigalian age. The end of the sedimentary succession (Bonifacio formation) is essentially represented by a pile of hydraulic dunes. The absence of Orbulina shows that this upper unit is older than late Langhian (biozone N9). Miocene sediments from Saint-Florent are divided into 3 marine formations bracketed by two continental ones. At the base, the continental formation of Fium’Albinu (equivalent to the Cala di Labra formation) is surmounted by the Torra formation attributed to Late Burdigalian based on the presence of G. trilobus and G. bisphericus. The Sant’Angelo formation (equivalent to the Bonifacio formation) developed from latest Burdigalian to late Langhian. The Farinole formation represents early Serravallian (base of the Globoquadrina altispira altispira zone). Despite the large number of studied sites in this study and others, the only reliable Oligo-Miocene paleomagnetic results in Corsica are the following ones : – the Vazzio formation indicates a rotation of 44 ± 4° after the late Oligocene, – the southern volcanic flows show that the rotation was in progress around 20.7 Ma (late Aquitanian), – the Fium’Albinu formation indicates a rotation of 30 ± 12° after early Burdigalian, – site B from Vigliotti and Kent [1990] gives a rotation of about 11 ± 5° after early Langhian. Our paleomagnetic data, together with the existing ones, associated to the biostratigraphic and geochronologic ages show that the opening of the Ligurian basin coincides with an anticlockwise rotation of 45° of Corsica, which begins between 23 and 21 Ma and ends around 15 Ma. This is in agreement with the idea of Sardinia and Corsica rotating as a single almost rigid block during Miocene times.

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