Spatial and temporal facies evolution of a Lower Jurassic carbonate platform, NW Tethyan margin (Mallorca, Spain)

The variety of depositional facies of a Lower Jurassic carbonate platform has been investigated on the island of Mallorca along a transect comprising six stratigraphic profiles. Twenty-nine facies and sub-facies have been recognized, grouped into seven facies associations, ranging in depositional environment from supratidal/terrestrial and peritidal to outer platform. Spatial and temporal (2D) facies distribution along the transect reflects the evolution of the carbonate platform with time showing different facies associations, from a broad peritidal platform (stage 1) to a muddy open platform (stage 2), and finally to a peritidal to outer carbonate platform (stage 3). Stage 1 (early Sinemurian to earliest late Sinemurian) corresponds to a nearly-flat peritidal-shallow subtidal epicontinental platform with facies belts that shifted far and fast over the whole study area. The evolution from stage 1 to stage 2 (late Sinemurian) represents a rapid flooding of the epicontinental shallow platform, with more open-marine conditions, and the onset of differential subsidence. During stage 3 (latest Sinemurian), peritidal and shallow-platform environments preferentially developed to the northeast (Llevant Mountains domain) with a rapid transition to middle-outer platform environments toward the northwest (Tramuntana Range domain). Stages 1 and 3 present facies associations typical of Bahamian-type carbonates, whereas stage 2 represents the demise of the Bahamian-type carbonate factory and proliferation of muddy substrates with suspension-feeders. The described platform evolution responded to the interplay between the initial extensional tectonic phases related to Early Jurassic Tethyan rifting, contemporaneous environmental perturbations, and progressive platform flooding related to the Late Triassic–Early Jurassic worldwide marine transgression and associated accommodation changes

Enhancing methotrexate tolerance with folate tagged liposomes in arthritic mice

Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance