The Upper Eocene South Pyrenean Coastal deposits (Liedena sandstone, navarre): Sedimentary facies, benthic formanifera and avian ichnology

Summary During the 1960's and the 1970's the Liedena Sandstone was a type deposit for “flysch-like facies” (sandstone and lutite alternations) of coastal sedimentary systems. However, the depositional system of these beds was never accurately defined. The sedimentological analysis along 100 km of outcrops in the western part of the South Pyrenean Zone (Navarre) allows these peculiar facies to be assigned to a mixed intertidal flat. Furthermore, sandy beach facies, different types of heterolithic, backbarrier deposits and conglomeratic, fluviatile facies have been recognized associated with these intriguing deposits. Generally, a northwestward-facing barrier-island system or wave-dominated delta was the likely depositional environment. The benthic foraminiferal assemblage in the intertidal deposits exhibits the typical characteristics of a marginal marine environment: extremely high dominance of one species (Pararotalia inermis), low species diversity, and a hyaline dominance with discrete amounts of miliolids. Furthermore, the most abundant species indicates that the Liedena Sandstone was deposited during the Late Eocene. Abundant footprints of aquatic birds are known in the tidal flat deposits. Six morphotypes have been distinguished: two (types 1 and 2) are ciconiforme-like; type 1 is here assigned to a new ichnotaxon,Leptoptilostipus pyrenaicus and is one of the oldest occurrences of Ciconiiforme-like ischmites in the fossil record. Two other morphotypes (5 and 6) are similar to those of the Charadriiformes and are refeered to asCharadriipeda. Finally, the affinities of the two remainder morphotypes (3 and 4) are unclear, they could have been made by Charadriiformes. Synsedimentary tectonic activity controlled the evolution of the depositional system, as the area of deposition of the Liedena Sandstone was progressively incorporated into the active thrust sheets of the Pyrenean Orogen during the Late Eocene. The structural uplift and the large amount of sediments derived from the adjacent highlands induced progradation of the depositional system and the definitive retreat of the sea from the South Pyrenean Zone.     

A study of the coordination shell of aluminum(III) and magnesium(II) in model protein environments: thermodynamics of the complex formation and metal exchange reactions

Al(III) toxicity in living organisms is based on competition with other metal cations. Mg(II) is one of the most affected cations, since the size similarity dominates over the charge identity. The slow ligand exchange rates for Al(III) render the ion useless as a metal ion at the active sites of enzymes and provide a mechanism by which Al(III) inhibits Mg(II) dependent biochemical processes. Al(III) cation interactions with relevant bioligands have been studied in a protein-model environment in gas and aqueous phases using density functional theory methods. The protein model consists of the metal cation bound to two chosen bioligands (functional groups of the amino acid side chains, one of them being always an acetate) and water molecules interacting with the cation to complete its first coordination shell. Analogous Mg(II) complexes are calculated and compared with the Al(III) ones. Formation energies of the complexes are calculated in both phases and magnesium/aluminum exchange energies evaluated. The effect of different dielectric media is also analyzed. The presence of an acetate ligand in the binding site is found to promote both, complex formation and metal exchange reactions. In addition, buried binding sites (with low dielectric constant) of the protein favor metal exchange, whereas fully solvated environments of high dielectric constant require the presence of two anionic ligands for metal exchange to occur.     

Visualization of the hybrid state of tRNA binding promoted by spontaneous ratcheting of the ribosome

A crucial step in translation is the translocation of tRNAs through the ribosome. In the transition from one canonical site to the other, the tRNAs acquire intermediate configurations, so-called hybrid states. At this stage, the small subunit is rotated with respect to the large subunit, and the anticodon stem loops reside in the A and P sites of the small subunit, while the acceptor ends interact with the P and E sites of the large subunit. In this work, by means of cryo-EM and particle classification procedures, we visualize the hybrid state of both A/P and P/E tRNAs in an authentic factor-free ribosome complex during translocation. In addition, we show how the repositioning of the tRNAs goes hand in hand with the change in the interplay between S13, L1 stalk, L5, H68, H69, and H38 that is caused by the ratcheting of the small subunit.     

Mechanism of low density lipoprotein (LDL) release in the endosome: implications of the stability and Ca2+ affinity of the fifth binding module of the LDL receptor

Uptake of low density lipoproteins (LDL) by their receptor, LDLR, is the primary mechanism by which cells incorporate cholesterol from plasma. Mutations in LDLR lead to familial hypercholesterolemia, a common disease affecting 1 in 500 of the human population. LDLR is a modular protein that uses several small repeats to bind LDL. The repeats contain around 40 residues, including three disulfide bonds and a calcium ion. Repeat 5 (LR5) is critical for LDL and beta-migrating very low density lipoprotein binding. Based on the crystal structure of LDLR at endosomal pH (but close to extracellular calcium concentration), LR5 has been proposed to bind to the epidermal growth factor (EGF) precursor domain of LDLR in the endosome, thus releasing the LDL particles previously bound in extracellular conditions. We report here the conformational stability of LR5 as a function of temperature and calcium concentration under both extracellular and endosomal pH conditions. The repeat was very stable when it bore a bound calcium ion but was severely destabilized in the absence of calcium and even further destabilized at acidic versus neutral pH. The temperature and calcium concentration dependence of LR5 stability clearly indicate that under endosomal conditions the unfolded conformation of the repeat is largely dominant. We thus propose a new mechanism for LDL release in the endosome in which calcium depletion and decreased stability at acidic pH drives LR5 unfolding, which triggers LDL release from the receptor. Subsequent binding of LR5 to the EGF precursor domain, if it takes place at low calcium concentrations, would contribute to a further shifting of the equilibrium toward dissociation.     

Development and experimental validation of a finite element model of total ankle replacement

Total ankle replacement remains a less satisfactory solution compared to other joint replacements. The goal of this study was to develop and validate a finite element model of total ankle replacement, for future testing of hypotheses related to clinical issues. To validate the finite element model, an experimental setup was specifically developed and applied on 8 cadaveric tibias. A non-cemented press fit tibial component of a mobile bearing prosthesis was inserted into the tibias. Two extreme anterior and posterior positions of the mobile bearing insert were considered, as well as a centered one. An axial force of 2 kN was applied for each insert position. Strains were measured on the bone surface using digital image correlation. Tibias were CT scanned before implantation, after implantation, and after mechanical tests and removal of the prosthesis. The finite element model replicated the experimental setup. The first CT was used to build the geometry and evaluate the mechanical properties of the tibias. The second CT was used to set the implant position. The third CT was used to assess the bone-implant interface conditions. The coefficient of determination (R-squared) between the measured and predicted strains was 0.91. Predicted bone strains were maximal around the implant keel, especially at the anterior and posterior ends. The finite element model presented here is validated for future tests using more physiological loading conditions.