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.     

Numerical modelling of calcination reaction mechanism for cement production

Calcination is a thermo-chemical process, widely used in the cement industry, where limestone is converted by thermal decomposition into lime CaO and carbon dioxide CO₂. The focus of this paper is on the implementation and validation of the endothermic calcination reaction mechanism of limestone in a commercial finite volume based CFD code. This code is used to simulate the turbulent flow field, the temperature field, concentrations of the reactants and products, as well as the interaction of particles with the gas phase, by solving the mathematical equations, which govern these processes. For calcination, the effects of temperature, decomposition pressure, diffusion and pore efficiency were taken into account. A simple three-dimensional geometry of a pipe reactor was used for numerical simulations. To verify the accuracy of the modelling approach, the numerical predictions were compared with experimental data, yielding satisfying results and proper trends of physical parameters influencing the process.     

Trace Elements in the Si Furnace-Part II: Analysis of Condensate in Carbothermal Reduction of Quartz

Silicon feedstock for production of solar-grade silicon should be as pure as possible to decrease the cost of manufacturing of solar cells. Impurities in quartz, carbonaceous materials, electrodes, and refractories are mostly present in the form of oxides. These oxides can be reduced to volatile gaseous compounds in presence of SiO(g) and CO(g) atmosphere and potentially leave the furnace or stay in the condensed reaction products, metal, and slag. This work investigates the conditions under which volatile impurities report to the gas phase in laboratory experiments with lumpy and pelletized mixtures of SiO₂, SiC, and Si at 1923 K and 2123 K (1650 °C and 1850 °C), respectively, were carried out. The volatile compounds were generated by the reduction of quartz and collected in the form of condensate. The effects of the reaction temperature, quartz type, charge composition, pellets, and lumps on the composition of the condensate were studied. The trace elements in the charge input, reacting charge, and condensate were analyzed using inductively coupled plasma (ICP)-mass spectroscopy (MS) and X-ray diffraction (XRD). CO(g) and SiO(g), which are the major components in reduction reactions, formed four types of condensate: white, brown, green, and orange. The condensate constituents were amorphous SiO₂, 3C:SiC, Si, and α-quartz. Each impurity present in the quartz charge entered the gas phase during quartz reduction and was detected in the condensate. Al and Fe show limited volatility. The volatility of Mn, P, and B depends on the charge mix: a higher P_CO enhances the concentration of these elements in the gas phase. Fluid inclusions, common in hydrothermal quartz, enhance the distribution of the contaminants to the gas phase. Industrial campaigns on Si and Fe-Si production confirm the experimental results.     

Strategies towards injectable, load-bearing materials for the intervertebral disc: a review and outlook

Currently available treatments for the degenerated intervertebral disc present disadvantages, such as surgical invasiveness and inadequate load distribution results. Load-bearing, injectable materials may be interesting for future therapies, but have not been studied in depth. In this study, the existing literature was screened for studies on injectable materials for the intervertebral disc and a rationale for load-bearing, injectable materials was formulated. Requirements for such a material were discussed, partly based on the experience of materials used for similar applications. Important properties were discussed and found to include biocompatibility, bioactivity, porosity, handling, injectability, working time, setting time, radiopacity, containment and mechanical properties, where several of these properties are linked to one another. In conclusion, there is a need for consensus on the properties of new materials developed for use in minimally invasive procedures in the spine. A substantial amount of attention may need to be given to non-toxic setting reactions.     

Alterations in gap junction connexin43/connexin45 ratio mediate a transition from quiescence to excitation in a mathematical model of the myometrium

The smooth muscle cells of the uterus contract in unison during delivery. These cells achieve coordinated activity via electrical connections called gap junctions which consist of aggregated connexin proteins such as connexin43 and connexin45. The density of gap junctions governs the excitability of the myometrium (among other factors). An increase in gap junction density occurs immediately prior to parturition. We extend a mathematical model of the myometrium by incorporating the voltage-dependence of gap junctions that has been demonstrated in the experimental literature. Two functional subtypes exist, corresponding to systems with predominantly connexin43 and predominantly connexin45, respectively. Our simulation results indicate that the gap junction protein connexin45 acts as a negative modulator of uterine excitability, and hence, activity. A network with a higher proportion of connexin45 relative to connexin43 is unable to excite every cell. Connexin45 has much more rapid gating kinetics than connexin43 which we show limits the maximum duration of a local burst of activity. We propose that this effect regulates the degree of synchronous excitation attained during a contraction. Our results support the hypothesis that as labour approaches, connexin45 is downregulated to allow action potentials to spread more readily through the myometrium.