Geologic carbon sources may confound ecosystem carbon balance estimates: Evidence from a semiarid steppe in the southeast of Spain

At a semiarid steppe site located in the SE of Spain, relatively large CO2 emissions were measured that could not be attributed to the ecosystem activity alone. Since the study site was located in a tectonically active area, it was hypothesized that a part of the measured CO2 was of geologic origin. This investigation included a survey of soil CO2 efflux, together with carbon isotope analyses of the CO2 in the soil atmosphere, soil CO2 efflux (ie, Keeling plots), groundwater and local thermal springs. These measurements confirmed the ... Articoli in Schola

Late orogenic doming in the Eastern Betics : final exhumation of the Nevado-Filabride complex and its relation to basin genesis.

The geometry, timing, and kinematics of late orogenic extension in the Betic Cordilleras pose the problem of a decoupling of upper crustal and lower crustal deformation regimes. Perpendicular directions of extension in metamorphic domes and nearby sedimentary basins remain unexplained. This paper puts kinematic constraints on the final exhumation of the Nevado-Filabride complex, focusing on the formation of metamorphic domes and their relations with the adjacent basins. Structural fabrics and kinematic indicators below the main shear zones as well as their relations with both published changing metamorphic P-T conditions and geochronological data were studied. Our approach describes (1) a consistent top-to-the-west shear parallel to dome axes of during D2 (i.e., during decompression) with distributed ductile flow and the onset of strain localization along major shear zones, (2) further strain localization along the major shear zones under greenschist facies conditions, during D3 leading to S-C′ mylonites formation accompanied with a rock strong thickness reduction, (3) the divergence of shear direction on either limbs of domes during D3 showing the appearance of the dome geometry, and (4) a local evolution toward N-S brittle extension (D4) in the upper plate and formation of sedimentary basins. Continuous ductile to brittle top-to-the-west shear is compatible with the slab retreat hypothesis from the Miocene; the formation of domes which adds gravitational forces responsible for the final stages of exhumation is thus characterized by important kinematics changes necessary to explain coeval N-S opened basins. Later, from the upper Tortonian, a contractional event (D5) amplified the earlier domal structures forming the present north vergent folds

Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: conformational analysis and binding mode of multisite inhibitors

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challeng- ing. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein— that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the bind- ing of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligo- methylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications intro- duced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors