Structural Cues for Understanding eEF1A2 Moonlighting

Spontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post-translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol-4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl-tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.     

7-Amidocoumarins as Multitarget Agents against Neurodegenerative Diseases: Substitution Pattern Modulation

This study explores the potential of 7-amidocoumarins as multitarget agents against Parkinson's and Alzheimer's diseases, by modulating the substitution patterns within the scaffold. Sixteen compounds were synthesized via 7-amino-4-methylcoumarin acylation, and in vitro evaluation of the molecules against hMAO-A, hMAO-B, hAChE, hBuChE and hBACE1 was performed. Five compounds turned out to be potent and selective hMAO-B inhibitors in the nanomolar range, six displayed inhibitory activity of hMAO-A in the low micromolar range, one showed hAChE inhibitory activity and another one hBACE1 inhibitory activity. MAO-B reversibility profile of 7-(4’-chlorobenzamido)-4-methylcoumarin ( 10 ) was investigated, with this compound being a reversible inhibitor. Neurotoxicity on motor cortex neurons and neuroprotection against H₂O₂ were also studied, corroborating the safety profile of these molecules. Finally, theoretical ADME properties were also calculated, showing these molecules as good candidates for the optimization of a lead compound. Results suggest that by modulating the substitution pattern at position 7 of the scaffold, selective or multitarget molecules can be achieved.     

The use of joint coordinates to monitor patients in a movement-based interaction system

Universal Access in the Information Society - Movement-based interaction has brought about new possibilities in healthcare environments. Concretely, rehabilitation therapies represent an adequate...     

Understanding the crispy–crunchy texture of raw red pepper and its change with storage time

Red sweet peppers held in cold storage were periodically sampled at 1-week intervals over a 3-weeks period using three-point bending, puncture, cutting, and Volodkevich (coupled with acoustic emission) tests, confocal laser scanning microscopy (CLSM) and other physicochemical measurements. At each sampling, tissue specimens were soaked in mannitol solutions (0.0–0.9M) and puncture test, dimension changes and CLSM were used to identify degrees of turgidity present in osmotically manipulated pepper tissue. Pepper texture became crumbly with increased storage time due to softening and wilting processes. The Young's modulus, derived from the bending test using the single-edge notched bend geometry without notches decreased progressively during cold storage and resulted as the best mechanical parameter for measuring the loss of whole-tissue stiffness by both decreased cell wall stiffness and turgor pressure. Osmotic adjustment indicated that the pepper structure is extremely anisotropic, with the specimen's “average” relative thickness (RT) being the dimension change more affected. Incipient plasmolysis was evident in the highest mannitol concentration (0.9M), therefore, the turgor pressure of nonsoaked tissue could not be inferred. However, significant correlations were found between RT and puncture parameters such as initial slope, initial and final distances, and the number of flesh and skin force peaks, which depended on the dilation or shrinkage caused by the osmotic adjustment. During storage, soaked tissues had lower crunchy texture than nonsoaked, reflecting that cell wall stiffness plays a more significant role in determining pepper crunchiness than cell turgor pressure.     

In vivo Kinetic Biodistribution of Nano‐Sized Outer Membrane Vesicles Derived from Bacteria

Evaluation of kinetic distribution and behaviors of nanoparticles in vivo provides crucial clues into their roles in living organisms. Extracellular vesicles are evolutionary conserved nanoparticles, known to play important biological functions in intercellular, inter‐species, and inter‐kingdom communication. In this study, the first kinetic analysis of the biodistribution of outer membrane vesicles (OMVs)—bacterial extracellular vesicles—with immune‐modulatory functions is performed. OMVs, injected intraperitoneally, spread to the whole mouse body and accumulate in the liver, lung, spleen, and kidney within 3 h of administration. As an early systemic inflammation response, increased levels of TNF‐α and IL‐6 are observed in serum and bronchoalveolar lavage fluid. In addition, the number of leukocytes and platelets in the blood is decreased. OMVs and cytokine concentrations, as well as body temperature are gradually decreased 6 h after OMV injection, in concomitance with the formation of eye exudates, and of an increase in ICAM‐1 levels in the lung. Following OMV elimination, most of the inflammatory signs are reverted, 12 h post‐injection. However, leukocytes in bronchoalveolar lavage fluid are increased as a late reaction. Taken together, these results suggest that OMVs are effective mediators of long distance communication in vivo.     

Surface and Groundwater Quality Evolution in the Agrio and Guadiamar Rivers After the Aznalcóllar Mine Spill (SW Spain): Lessons Learned

Mine Water and the Environment - The failure of the tailing dam at the Aznalcóllar mine (SW Spain) in 1998 released ≈ 6 million m3 of pyrite sludge and acidic...