Cellular Redox Metabolism Is Modulated by the Distinct Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms

3′-5′ cyclic nucleotide phosphodiesterases (PDEs) are a family of evolutionarily conserved cAMP and/or cGMP hydrolyzing enzymes, components of transduction pathways regulating crucial aspects of cell life. Among them, cGMP-specific PDE5—being a regulator of vascular smooth muscle contraction—is the molecular target of several drugs used to treat erectile dysfunction and pulmonary hypertension. Production of full-length murine PDE5A isoforms in the milk-yeast Kluyveromyces lactis showed that the quaternary assembly of MmPDE5A1 is a mixture of dimers and tetramers, while MmPDE5A2 and MmPDE5A3 only assembled as dimers. We showed that the N-terminal peptide is responsible for the tetramer assembly of MmPDE5A1, while that of the MmPDE5A2 is responsible for its mitochondrial localization. Overexpression of the three isoforms alters at different levels the cAMP/cGMP equilibrium as well as the NAD(P)⁺/NAD(P)H balance and induces a metabolic switch from oxidative to fermentative. In particular, the mitochondrial localization of MmPDE5A2 unveiled the existence of a cAMP-cGMP signaling cascade in this organelle, for which we propose a metabolic model that could explain the role of PDE5 in some cardiomyopathies and some of the side effects of its inhibitors.     

Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods

The aim of the present paper was the development of semi-solid (hydrogels) and solid (film) ophthalmic formulations for the controlled release of two mydriatics: phenylephrine and tropicamide. The formulations – based on polyvinylalcohol and hyaluronic acid – were characterized, and release studies were performed with three different in vitro set-ups, i.e. Franz-type diffusion cell, vial method and inclined plane; for comparison, a solution and a commercial insert, both clinically used to induce mydriasis, were evaluated. Both gels and film allowed for a controlled release of drugs, appearing a useful alternative for mydriatics administration. However, the release kinetic was significantly influenced by the method used, highlighting the need for optimization and standardization of in vitro models for the evaluation of drug release from ophthalmic dosage forms.     

Influence of two structural phases of Fe3O4 and γ‐Fe2O3 on the properties of polyimide/iron oxide composites

Partially aliphatic polyimide/iron oxide composites based on the poly(amic acid) from 5‐(2,5‐dioxotetrahydro‐3‐furyl)‐3‐methyl‐3‐cyclohexene‐1,2‐dicarboxylic acid anhydride and 4,4′‐oxydianiline with iron oxide in different weight percentages were obtained. The structural phases of the transition of magnetite to maghemite occurring in these composites, at different temperatures, are discussed. The physical characteristics, including magnetic, thermal, structural and morphological properties, evaluated using X‐ray diffraction, scanning electron microscopy and thermal analysis, are influenced by the interplay of the filler content and the structural changes of the composite. The X‐ray diffraction patterns of all samples show a cubic structure indexed as magnetite (Fe₃O₄) or maghemite (γ‐Fe₂O₃). Quantification of these two phases was evidenced by the Rietveld method. The electrical properties analysed under different humidity conditions evidence the potential applicability of these polyimide/iron oxide materials as humidity sensors. © 2015 Society of Chemical Industry     

Production,mode of action and sequencing of the corresponding gene of a bacteriocin produced by Lactococcus lactis 19.3

Lactococcus lactis 19.3 produces a bacteriocin with a wide inhibitory spectrum, including the food pathogen Listeria monocytogenes. The producing strain was able to grow and produce similar amounts of bacteriocin in MRS medium, cow's milk and soya milk, respectively. The mode of action of this bacteriocin was further investigated using two indicator strains, Lactobacillus delbrueckii subsp. bulgaricus LMG 6901^T and Listeria monocytogenes ATCC 1911‐1. The bacteriocin displayed a bactericidal effect, causing a rapid decrease of the cell viability. Bacteriocin treatment of the sensitive strains resulted in major morphological changes, including pore formation, as shown by scanning electron microscopy. Finally, the bacteriocin‐encoding gene was identified by sequencing. The presence of nisin gene was confirmed. Based on all our data gathered so far, L. lactis 19.3 is a good candidate for a starter or protective culture in the manufacturing of both fermented dairy and vegetarian food products.     

Polymer-interaction driven diffusionof eyeshadow in soft contact lenses

Soft contact lenses used for the correction of ametropia are often made of hydrogel and silicone-hydrogel materials. Since they are placed directly on the surface of the eye and they are hydrated by tears, eye cosmetics can compromise the lens performance and, even worse, can be transported from an external environment to the ocular surface through the contact lens.The diffusion of the dye component of a purple eyeshadow in soft contact lenses of different materials is here evaluated. Diffusivity is found to be typically higher in silicone-hydrogels than in hydrogels. In hydrogels, diffusivity is greater in the case of lower oxygen transmissibility. Despite differences between materials, absorbed mass of dye is much larger (10–100 times) than the expected mass by simple hydration and swelling of the contact lens. The most contaminated materials are also resistant to cleaning solutions. The results indicate that, notwithstanding the complexity of contact lens networks, diffusion of dye is found to follow Fick’s law and it is driven by polymer-dye interaction, which governs lens hydration and swelling.     

Consumer interpretations of digital ownership in the book market

Technological advances in electronic markets, particularly product digitization, have transformed customer-product interactions. For example, altered ownership perceptions in the digital domain affect product acquisition, usage and disposition. This study’s goal is to explore how consumers conceptualize ownership of digital possessions in order to help marketers develop tailored positioning and commercialization strategies. Comparing physical books and e-books, we contribute to the literature on electronic markets, which neglects a consumer-focused perspective on digital possessions. Using focus groups with U.S. consumers, we identify six themes surrounding perceptions of psychological digital ownership, which mainly portray a constricted sense of ownership, limiting usage experience, and value perceptions. However, we also find that ease of disposition favors e-book usage. Typical assumptions about younger consumers’ preference for digital products were not supported. Based on our findings, we offer two managerial approaches: (1) enhancing the digital product experience or (2) emancipating digital products from their physical correlates.