The raison d'être of constitutively active protein kinases: the lesson of CK2

Protein kinases generally are tightly controlled signaling molecules that are switched on only in response to specific stimuli. Exceptionally few protein kinases are constitutively active, the most striking example being provided by CK2 (formerly "casein kinase 2"). Owing to unique structural features, the catalytic activity of CK2 is constantly on, although its targeting can be deeply influenced by the association of its two catalytic subunits (alpha and/or alpha') with a dimeric non catalytic beta subunit. Constitutive activity of CK2 reflects its extraordinary pleiotropy documented by its growing list of >300 protein substrates and is consistent with emerging evidence that CK2 plays an essential role in the cell by counteracting premature and/or unscheduled apoptosis, thus ensuring cell survival under stress conditions.     

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.     

Sol–Gel Processing and Characterization of Pure and Metal-Doped SnO2 Thin Films

A chloride-based inorganic sol–gel route was used for preparing pure and metal (osmium, nickel, palladium, platinum)-doped SnO₂ sol. SnCl₄ was first reacted with propanol, then the resulting compound was hydrolyzed and subsequently mixed with solutions of the metal dopants. The obtained sols were used for depositing thin films by spin coating or for preparing powders by solvent evaporation at 110°C. FTIR spectroscopy and thermal analysis of the powders revealed that chlorine still bound to tin stabilized the sol against gelation by hindering the condensation reactions. Film characterizations showed that platinum and palladium, unlike nickel and osmium, were likely to form nanoparticles in the SnO₂ lattice. This result was discussed with regard to the different ways that platinum and palladium, on one hand, and nickel and osmium, on the other, modified the growth of SnO₂ grains and the film roughness and morphology. Dopants that formed nanoparticles (platinum, palladium) resulted in the roughest film, while dopants that did not form particles (nickel, osmium) resulted in SnO₂ grain size very close to that of pure SnO₂.     

Peculiar crystallization kinetics of biodegradable poly(lactic acid)/poly(propylene carbonate) blends

Binary blends of poly(lactic acid) (PLA) and poly(propylene carbonate) (PPC) were found to display a peculiar crystallization kinetics. The two biodegradable polymers were blended by melt mixing, to obtain binary blends at various compositions. Temperature‐modulated calorimetry and dynamic‐mechanical analysis indicated that the blend components are partially miscible, and display two separate glass transitions, at temperatures intermediate to those of the plain polymers. Electron microscopy analysis disclosed the morphology of PLA/PPC blends, made of PPC‐rich particles finely dispersed within the PLA‐rich matrix. The possible establishment of interactions between the functional groups of the two polymers upon melt mixing has been hypothesized as the reason for partial miscibility and compatibility of the two biodegradable polymers. The PLA/PPC blends display good mechanical properties, with enhanced performance at rupture compared with plain PLA. Most importantly, the addition of PPC affects also the crystallization kinetics of PLA, since the more mobile PPC chains favor diffusion of the stiffer PLA chain segments towards the growing crystals, which fastens the spherulite growth rate of PLA. Such positive influence of an amorphous polymer on crystal growth rate has been demonstrated here for the first time in blends that display phase‐separation in the melt. POLYM. ENG. SCI., 55:2698–2705, 2015. © 2015 Society of Plastics Engineers     

Adamantyl Arotinoids That Inhibit IκB Kinase α and IκB Kinase β

A series of analogues of the adamantyl arotinoid (AdAr) chalcone MX781 with halogenated benzyloxy substituents at C2′ and heterocyclic derivatives replacing the chalcone group were found to inhibit IκBα kinase α (IKKα) and IκBα kinase β (IKKβ) activities. The growth inhibitory capacity of some analogues against Jurkat T cells as well as prostate carcinoma (PC‐3) and chronic myelogenous leukemia (K562) cells, which contain elevated basal IKK activity, correlates with the induction of apoptosis and increased inhibition of recombinant IKKα and IKKβ in vitro, pointing toward inhibition of IKK/NFκB signaling as the most likely target of the anticancer activities of these AdArs. While the chalcone functional group present in many dietary compounds has been shown to mediate interactions with IKKβ via Michael addition with cysteine residues, AdArs containing a five‐membered heterocyclic ring (isoxazoles and pyrazoles) in place of the chalcone of the parent system are potent inhibitors of IKKs as well, which suggests that other mechanisms for inhibition exist that do not depend on the presence of a reactive α,β‐unsaturated ketone.     

Generation of Nanoparticles with a Nebulizer-Cyclone System

A cyclone was used to modify the droplet output with a three-jet Collison nebulizer. The cyclone-nebulizer system was tested by producing ammonium fluorescein particles from a liquid suspension. The particle size distribution produced with the cyclone was smaller and narrower than that produced without the cyclone. Thus, the cyclone effectively removed the large droplets produced by the nebulizer. The nebulizer-cyclone system reduced the GSD of the output aerosol from 1.7 to 1.4. At the input pressures greater than 138 kPa, the concentration of 10–60 nm particles was greater with the cyclone than without the cyclone. These results are consistent with the shattering of large droplets within the cyclone and re-entrainment of these small secondary droplets. Optimization of the system using cyclone modeling to enhance the sharpness of cut, operational improvements, and decreased venting could maximize the output of tailored distributions of nanoparticles for various applications.     

Wooden window frames with structural sealants: manufacturing improvements and experimental validation of a finite element model

This paper proposes a finite element (FE) model of a novel wooden window frame typology and validates it by experimental tests on window frames and corner joint specimens. The innovation consists of the application of the structural silicone sealant only at the interface between wood and one of the thin glass layers of the double-glazing glass, so achieving a low application depth. This technique reduces the sealant quantity and allows the disassembly and substitution of the glass from the frame in case of breakage. In order to inform the FE model of the whole frame, the dowelled butt corner joint strength is measured by specific experimental tests. The results show a good correlation between the FE model and the experimental results in the range of small frame deformations, which are of interest for the proposed application. In particular, the FE curve overestimates the bottom corner displacement of about 17% at 1000?N load, 7% at 2000?N and less than 5% at higher applied force on the upper corner. The model is then applied to various wooden frame geometries in order to evaluate if the proposed silicone application mode and dowelled corner joints type allow an acceptable stiffness of the frame, and, in particular, low deformations of the bottom corner joint, in order to maintain the wooden frame functionality when subject to external loads. The approach could be useful when assessing optimal sealing application modes, wood-sealant-glass joint geometries, corner joint geometries and window frame geometries to limit the bottom corner joint deformation within the required technical specifications.     

Fungal fucoidanase production by solid-state fermentation in a rotating drum bioreactor using algal biomass as substrate

Fucoidanase enzymes able to degrade fucoidan were produced by solid-state fermentation (SSF). The fermentation assays were initially carried out in a laboratory-scale rotating drum bioreactor, and two fungal strains (Aspergillus niger PSH and Mucor sp. 3P) and three algal substrates (untreated, autohydrolyzed, and microwave processed seaweed Fucus vesiculosus) were evaluated. Additionally, fermentations were carried out under rotational (10 rpm) and static conditions in order to determine the effect of the agitation on the enzyme production. Agitated experiments showed advantages in the induction of the enzyme when compared to the static ones. The conditions that promoted the maximum fucoidanase activity (3.82 U L^?1) consisted in using Mucor sp. 3P as fungal strain, autohydrolyzed alga as substrate, and the rotational system. Such conditions were subsequently used in a 10 times larger scale rotating drum bioreactor. In this step, the effect of controlling the substrate moisture during the enzyme production by SSF was investigated. Moreover, assays combining the algal substrate with an inert support (synthetic fiber) were also carried out. Fermentation of the autohydrolyzed alga with the moisture content maintained at 80% during the fermentation with Mucor sp. 3P gave the highest enzyme activity (9.62 U L^?1).     

Gold(I)‐Catalysed Cyclisation of Alkynoic Acids: Towards an Efficient and Eco‐Friendly Synthesis of γ‐, δ‐ and ϵ‐Lactones

The improved synthesis of γ‐, δ‐ and ϵ‐lactones using a dinuclear N‐heterocyclic carbene (NHC)‐gold(I) catalyst is reported. This solvent‐free process provides access to γ‐ and δ‐lactones in high regio‐ and stereoselectivity. Reactions were performed at low catalyst loadings and without the need for any additives. The use of a digold pre‐catalyst provides a new synthetic route to functionalised ϵ‐lactones, poorly accessible using previous methodologies.