Geranylgeraniol and Neurological Impairment: Involvement of Apoptosis and Mitochondrial Morphology

Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate pathway and the consequent neurodegeneration. The blocking of the mevalonate pathway in a neuronal cell line (Daoy), using statins or mevalonate, induced an increase in the expression of the inflammasome gene (NLRP3) and programmed cell death related to mitochondrial dysfunction. The morphology of the mitochondria changed, clearly showing the damage induced by oxidative stress and the decreased membrane potential associated with the alterations of the mitochondrial function. The co-administration of geranylgeraniol (GGOH) reduced the inflammatory marker and the damage of the mitochondria, maintaining its shape and components. Our data allow us to speculate about the mechanism by which isoprenoids are able to rescue the inflammatory marker in neuronal cells, independently from the block of the mevalonate pathway, and about the fact that cell death is mitochondria-related.     

Electrochemical impedance spectroscopy study of a surface confined redox reaction: The reduction of azobenzene on mercury in the absence of diffusion

The kinetics of azobenzene reduction on mercury electrodes in the absence of diffussional mass transport is studied by electrochemical impedance spectroscopy (EIS) in acetic acid/acetate buffered solutions at different pH values. Cyclic voltammetry experiments confirm the absence of diffusion effects and provide the values of the surface equilibrium potential. The analysis of the impedance frequency spectrums at every potential within the faradaic region conforms well the model and provides the global rate constant of the process, k_f. The potential dependence of k_f suggests the existence of an EE mechanism, with two electron transfers controlling the overall rate. The kinetic parameters of every step are obtained and their pH dependences clarify the role played by the protonation steps.     

Cellulose nanocomposites based on silane reinforced 3-butynoate-substituted zirconium-oxocluster copolymers: Mechanical,thermal and hydrophobic properties

Silica based cellulose nanocomposites obtained from (3-mercaptopropyl)trimethoxysilane or vinyltrimethoxysilane and 3-butynoate-substituted zirconium-oxoclusters were prepared and their surface morphology, wettability, and thermo-mechanical properties were studied. The composites showed a hydrophobic surface, high strength, and resistance to thermal degradation and aging; in comparison to the untreated paper they required a higher temperature to activate combustion and generated less heat during all thermal processes.     

Tracking Hidden Binding Pockets Along the Molecular Recognition Path of l-Trp to Indoleamine 2,3-Dioxygenase 1

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the oxidative cleavage of l -Tryptophan (l -Trp) to yield N-formyl-kynurenine in the first and rate limiting step of the kynurenine pathway. Bioactive metabolites, involved in the regulation of important immunological responses and neurological processes, are then produced by downstream enzymes along the pathway. Inhibitors of IDO1 are being designed and developed as therapeutic agents for immuno-oncology. In this work, we investigated the molecular recognition path of l -Trp to IDO1, integrating biophysical methods with supervised molecular dynamics (suMD) and mutagenesis experiments. Results allowed disclosing for the first time high and low dissociation constants of l -Trp to IDO1, and the presence of a metastable interaction site located at the upper part of a channel whose borders are defined by the EF-loop and the C-terminal part of the JK-loop. Collectively, our results provide new clues for the design of next-generation IDO1 ligands.     

Intentional and unintentional contributions of nonspecific preparation during reaction time foreperiods.

The nonspecific preparation that follows a warning stimulus (WS) to speed responding to an impending imperative stimulus (IS) is generally viewed as a strategic, intentional process. An alternative view holds that WS acts as a conditioned stimulus that unintentionally elicits a tendency to respond at the moment of IS presentation as a result of a process of trace conditioning. These views were contrasted as explanatory frameworks for classical effects on reaction time of the duration and intertrial variability of the foreperiod, the interval between WS and IS. It is shown that the conditioning view accounts for the available data at least as well as the strategic view. In addition, the results of 3 experiments provide support for the conditioning view by showing that unintentional contributions to nonspecific preparation can be dissociated from intentional contributions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of magnetic and structural properties of cobalt thin films by means of electrodeposition

Cobalt electrodeposits were prepared from an electrolytic bath containing cobalt perchlorate. The effect of different species, organic (thiourea and sodium gluconate) and inorganic (boric acid), on the crystallographic structure, morphology, magnetic properties and electrochemical behaviour of cobalt electrodeposits was investigated. Amorphous cobalt, hcp cobalt and a non-usual primitive cubic cobalt phase were observed depending on the bath composition. Depending on the structure, different morphologies and magnetic properties were found. Coercivity values of the cobalt coatings ranged from around 15 Oe for amorphous, nodular deposits to 380 Oe for cobalt coatings showing acicular morphology and hcp structure with a (002) preferred orientation. Knowledge of the influence of the species on the properties of cobalt makes it possible to obtain tailored cobalt films.     

Design Recommendations for a FRP Bridge Deck Supported on Steel Superstructure

No appropriate provisions from either AASHTO Standard (2002) or AASHTO LRFD (2004) bridge design specifications are available for the design of fiber-reinforced polymer (FRP)-deck-on-steel-superstructure bridges. In this research, a parametric study using the finite-element method (FEM) is conducted to examine two design issues concerning the design of FRP-deck-on-steel-superstructure bridges, namely deck relative deflection and load distribution factor (LDF). Results show that the strip method specified in AASHTO LRFD specification as an approximate method of analysis, can also be applied to FRP decks as a practical method. However, different strip width equations have to be determined by either FEM or experimental methods for different types of FRP decks. In this study, one such equation has been derived for the Strongwell deck. In addition, both FEM results and experimental measurements show that the AASHTO LDF equations for glued laminated timber decks on steel stringers provide good estimations of LDF for FRP-deck-on-steel-superstructure bridges. Finally, it is found that the lever rule can be used as an appropriately conservative design method to predict the LDF of FRP-deck-on-steel-superstructure bridges.