Selective Inhibition of Helicobacter pylori Carbonic Anhydrases by Carvacrol and Thymol Could Impair Biofilm Production and the Release of Outer Membrane Vesicles

Helicobacter pylori, a Gram-negative neutrophilic pathogen, is the cause of chronic gastritis, peptic ulcers, and gastric cancer in humans. Current therapeutic regimens suffer from an emerging bacterial resistance rate and poor patience compliance. To improve the discovery of compounds targeting bacterial alternative enzymes or essential pathways such as carbonic anhydrases (CAs), we assessed the anti-H. pylori activity of thymol and carvacrol in terms of CA inhibition, isoform selectivity, growth impairment, biofilm production, and release of associated outer membrane vesicles-eDNA. The microbiological results were correlated by the evaluation in vitro of H. pylori CA inhibition, in silico analysis of the structural requirements to display such isoform selectivity, and the assessment of their limited toxicity against three probiotic species with respect to amoxicillin. Carvacrol and thymol could thus be considered as new lead compounds as alternative H. pylori CA inhibitors or to be used in association with current drugs for the management of H. pylori infection and limiting the spread of antibiotic resistance.     

Modelling the evolution of oxidative browning during storage of white wines: effects of packaging and closures

Shelf life of products is a key parameter for any company at local and international level that wish to improve their competitiveness; thus, there is a need to search for methods that allow one to predict the shelf life of bottled wines. In this view, the progress of chemical oxidative reactions of six Italian white wines during storage (10 months after bottling), in different packaging, was monitored by means of selected oenological parameters. The optical density at 420 nm, an index of browning, showed a progressive increase that fitted the zero‐order kinetic rate. The onset of wine browning was further tested by means of accelerated ageing in controlled temperature conditions which results, modelled using the rate constants approach, showed an Arrhenius‐like dependence from temperature, allowing to estimate apparent activation energies of oxidative chemical browning (range: 46.8–88.3 kJ mol^?1). Kinetic and thermodynamic approach provided a useful tool to predict quality changes of white wines during storage with respect to packaging conditions.     

Specificity of Infant Digestive Conditions: Some Clues for Developing Relevant In Vitro Models

Digestion of nutrients is an essential function of the newborn infant gut to allow growth and development and understanding infant digestive function is essential to optimize nutrition and oral drug delivery. Ethical considerations prohibit invasive in vivo trials and as a consequence in vitro assays are often conducted. However, the choice of in vitro model parameters are not supported by an exhaustive analysis of the literature and do not mimic precisely the digestive conditions of the infant. This review contains a compilation of the studies which characterized the gastroduodenal conditions in full-term or preterm infants of variable postnatal age from birth up to six months. Important data about healthy full-term infants are reported. The enzymatic (type of enzymes and level of activity) and nonenzymatic (milk-based diet, frequency of feeding, bile salt concentrations) conditions of digestion in infants are shown to differ significantly from those in adults. In addition, the interindividual and developmental variability of the digestive conditions in infants is also highlighted.     

Antineurogenic phenotypes induced by truncated Notch proteins indicate a role in signal transduction and may point to a novel function for Notch in nuclei

Loss of any one of several neurogenic genes of Drosophila results in overproduction of embryonic neuroblasts at the expense of epidermoblasts. In this paper a variety of altered Notch proteins are expressed in transgenic flies. Dominant lethal, antineurogenic phenotypes were produced by expression of three classes of mutant proteins: (1) a protein comprised of the cytoplasmic domain of Notch and devoid of sequences permitting membrane association; (2) a transmembrane protein lacking the extracellular, lin12/Notch repeats; and (3) transmembrane proteins carrying amino acid substitutions replacing one or both extracellular cysteines thought to be involved in Notch dimerization. These Notch proteins not only suppress the neural hypertrophy observed in Notch- embryos, but also generate a phenotype in which elements of the embryonic nervous system are underproduced. Action of the intracellular cdc10 repeats appears to be essential for wild-type Notch function or for the antineurogenic activity of these proteins. The activities of the dominant, gain-of-function proteins indicate that Notch functions as a signal transducing receptor during ectoderm development. Production of antineurogenic Notch proteins in embryos deficient for the other neurogenic genes allowed functional dependencies to be established. Delta, mastermind, bigbrain, and neuralized appear to function in elaboration of a signal upstream of Notch. Genes of the Enhancer of split complex act after Notch. The cytoplasmic domain of Notch contains nuclear localization sequences that function in cultured cells, and one of the Notch antineurogenic proteins, the cytoplasmic domain, accumulates in nuclei in vivo.     

On the role of the calcination step in the preparation of active (superacid) sulfated zirconia catalysts

In the preparation of active SO₄-ZrO₂ catalysts, several steps involving various chemical and/or physical processes are necessary. In particular it has been reported that, after sulfation of amorphous Zr hydrates, a calcination atT _calc>773 K is needed to guarantee the crystallization of ZiO₂ in the tetragonal phase. By the use of a stabilized tetragonal ZrO₂, it is here demonstrated that a calcination atT _calc>773 K is indeed necessary for all SO₄-ZrO₂ systems, and that its actual role is the selective elimination of sulfates from highly energetic crystallographic defects. The calcination step atT _calc>773 K so creates the conditions for the formation of strong Lewis acid centres, that are necessary in the catalytic process, and the presence of which is here monitored spectroscopically by the reversible adsorption of carbon monoxide.     

GUEST EDITORIAL: PAPERS IN SENSING AND IN REASONING (MARCO SOMALVICO MEMORIAL ISSUE)

Recently, we observed a great movement of Internet users from blogs and wiki to Myspace, Facebook, Twitter, and Plurk. To increase profit margins, identifying the service factors that attract customers to join a new virtual community is crucial for website enterprises. Most works focus on social networks, success factors, and reasons for participating. Relatively few works have attempted to address this issue. Additionally, feature selection techniques have been widely used to extract crucial attributes. However, domain knowledge, which is hard to obtain, is needed to select meaningful features. Therefore, this work proposes a Kano's model based Neural Network (KANN) method combining Kano's model and neural networks to identify the key service factors. Finally, a real case study of a survey of virtual community users is provided to identify the key service factors.     

Stochastic maximum principle for SPDEs with noise and control on the boundary

In this paper we prove necessary conditions for optimality of a stochastic control problem for a class of stochastic partial differential equations that is controlled through the boundary. This kind of problem can be interpreted as a stochastic control problem for an evolution system in a Hilbert space. The regularity of the solution of the adjoint equation, that is a backward stochastic equation in infinite dimension, plays a crucial role in the formulation of the maximum principle.     

Oxidative transformation of aqueous phenolic mixtures by birnessite-mediated catalysis

The catalytic efficiency of birnessite in the removal of catechol, hydroxytyrosol, methylcatechol and m-tyrosol, four phenols commonly present in polluted wastewaters, was studied in mono-substrate solutions or in mixtures of two, three, and four substrates. In single phenolic solutions the transformation order of phenols was catechol>hydroxytyrosol>methylcatechol>m-tyrosol. With phenolic mixtures different responses were observed and the amount of each phenol transformed and the crossing effects among the various phenols depended on the type and number of phenols present in the mixture. In particular, general inhibitory effects were observed for hydroxytyrosol and m-tyrosol that were transformed less when present in combination with the other phenols. By contrast the effects by the presence of more than one phenol were basically annulled for catechol and methylcatechol at 24 h incubation in all the mixtures. A simultaneous, but often no stoichiometric, release of soluble Mn2+ in the reaction mixtures occurred. The multi-substrate systems were designed to mimic birnessite-mediated oxidative processes that could occur under field conditions. Therefore they could be of great interest to environmental and soil science. The use of birnessite as a potential tool for an effective detoxification and recovery of phenol-polluted systems could be also envisaged.     

Carbonic anhydrase inhibitors: binding of indanesulfonamides to the human isoform II

Indanesulfonamides are interesting lead compounds for designing selective inhibitors of the different isoforms of the zinc enzyme Carbonic Anhydrase (CA). Herein, we report for the first time the X-ray crystal structure of two such derivatives, namely indane-5-sulfonamide and indane-2-valproylamido-5-sulfonamide, in complex with the physiologically dominant human isoform II. The structural analysis reveals that, although these two inhibitors have quite similar chemical structures, the arrangement of their indane ring within the enzyme active site is significantly diverse. Thus, our findings suggest that the introduction of bulky substituents on the indane-sulfonamide ring may alter the binding mode of this potent class of CA inhibitors, although retaining good inhibitory properties. Accordingly, the introduction of bulky tail moieties on the indane-sulfonamide scaffold may represent a powerful strategy to induce a desired physicochemical property to an aromatic sulfonamide or to obtain inhibitors with diverse inhibition profiles and selectivity for various mammalian CAs.