Antifungal Activity and DNA Topoisomerase Inhibition of Hydrolysable Tannins from Punica granatum L.

Punica granatum L. (pomegranate) fruit is known to be an important source of bioactive phenolic compounds belonging to hydrolysable tannins. Pomegranate extracts have shown antifungal activity, but the compounds responsible for this activity and their mechanism/s of action have not been completely elucidated up to now. The aim of the present study was the investigation of the inhibition ability of a selection of pomegranate phenolic compounds (i.e., punicalagin, punicalin, ellagic acid, gallic acid) on both plant and human fungal pathogens. In addition, the biological target of punicalagin was identified here for the first time. The antifungal activity of pomegranate phenolics was evaluated by means of Agar Disk Diffusion Assay and minimum inhibitory concentration (MIC) evaluation. A chemoinformatic analysis predicted for the first time topoisomerases I and II as potential biological targets of punicalagin, and this prediction was confirmed by in vitro inhibition assays. Concerning phytopathogens, all the tested compounds were effective, often similarly to the fungicide imazalil at the label dose. Particularly, punicalagin showed the lowest MIC for Alternaria alternata and Botrytis cinerea, whereas punicalin was the most active compound in terms of growth control extent. As for human pathogens, punicalagin was the most active compound among the tested ones against Candida albicans reference strains, as well as against the clinically isolates. UHPLC coupled with HRMS indicated that C. albicans, similarly to the phytopathogen Coniella granati, is able to hydrolyze both punicalagin and punicalin as a response to the fungal attack. Punicalagin showed a strong inhibitory activity, with IC₅₀ values of 9.0 and 4.6 µM against C. albicans topoisomerases I and II, respectively. Altogether, the results provide evidence that punicalagin is a valuable candidate to be further exploited as an antifungal agent in particular against human fungal infections.     

The Importance of N186 in the Alpha-1-Antitrypsin Shutter Region Is Revealed by the Novel Bologna Deficiency Variant

Alpha-1-antitrypsin (AAT) deficiency causes pulmonary disease due to decreased levels of circulating AAT and consequently unbalanced protease activity in the lungs. Deposition of specific AAT variants, such as the common Z AAT, within hepatocytes may also result in liver disease. These deposits are comprised of ordered polymers of AAT formed by an inter-molecular domain swap. The discovery and characterization of rare variants of AAT and other serpins have historically played a crucial role in the dissection of the structural mechanisms leading to AAT polymer formation. Here, we report a severely deficient shutter region variant, Bologna AAT (N186Y), which was identified in five unrelated subjects with different geographical origins. We characterized the new variant by expression in cellular models in comparison with known polymerogenic AAT variants. Bologna AAT showed secretion deficiency and intracellular accumulation as detergent-insoluble polymers. Extracellular polymers were detected in both the culture media of cells expressing Bologna AAT and in the plasma of a patient homozygous for this variant. Structural modelling revealed that the mutation disrupts the hydrogen bonding network in the AAT shutter region. These data support a crucial coordinating role for asparagine 186 and the importance of this network in promoting formation of the native structure.     

Ivermectin residues in milk of lactating donkey (Equus asinus): current regulation and challenges for the future

Ivermectin (IVM) is a macrocyclic disaccharide anthelmintic agent with broad-spectrum antiparasitic action. It is used for controlling internal and external parasites in food-producing animals (bovine, swine and equine species), including donkey. This drug is included in Council Regulation (EEC) 2377/90, annex I, with Maximum Residue Limit (MRL) ranging from 15 to 100???g?kg^?1 depending on the species. The pharmacokinetic characteristics of IVM mainly depend on the animal species, formulation and route of administration. Due to its high lipophilicity it accumulates in milk of food producing animals. Detailed IVM pharmacokinetic studies were carried out for horse, pig, cattle, sheep, and goat, but there is lack of information for asinine species. Consequently, the absence of ??label milk withdrawal time?? and MRLs in donkey??s milk indicates that IVM should not be used in lactating animals. On the contrary, information about IVM residues in milk would be of paramount importance in view of the fact that donkey??s milk is a suggested substitute for infants suffering from hypersensitivity to cow??s, sheep??s and goat??s milk protein or from multiple hypersensitivity. European legislation does not explicitly state that an MRL should be determined for every target species; however it??s interpretation led to MRLs being adopted for each species and each foodstuff. Although IVM is approved for use in all lactating animal species the possibility of an illegal use should be considered. In this paper, the problems arising from IVM administration in lactating donkey are analysed. A particular attention is paid for the existing legislation and some proposals are suggested for regulatory framework formulation.     

All-optical integrated micro logic gate

In this paper we present a novel approach for realizing an integrated all-optical logic gate. The basic principle is based upon stimulated emission process generated in an active gain medium while special interferometric photonic wave-guiding structure allows the realization of an integrated micro scale device. The operation rate of the proposed device structure can theoretically reach tens of Tera-Hertz.     

Influence of Boundary Conditions in a Finite-Element Analysis of River Levees

The effects of boundary conditions on the stability of a river levee built on a low-permeability soil layer overlying a coarse-grained deposit were studied by using the finite-element method (FEM). The FEM analyses could predict stable or unstable levee conditions depending on the assumed distance between the levee and the external boundary of the mesh where the water table was assumed undisturbed. Possible causes of this notable drawback are discussed. The calibration of the numerical seepage model, through a back analysis of piezometer measurements, that could limit the observed boundary effects is suggested.     

Influence of Ion Induced Local Coulomb Field and Polarity on Charge Generation and Efficiency in Poly(3‐Hexylthiophene)‐Based Solid‐State Dye‐Sensitized Solar Cells

Dye‐sensitized solar cells (DSSC) are a realistic option for converting light to electrical energy. Hybrid architectures offer a vast materials library for device optimization, including a variety of metal oxides, organic and inorganic sensitizers, molecular, polymeric and electrolytic hole‐transporter materials. In order to further improve the efficiency of solid‐state dye‐sensitized solar cells, recent attention has focused on using light absorbing polymers such as poly(3‐hexylthiophene) (P3HT), to replace the more commonly used “transparent” 2,2′,7,7′‐tetrakis‐(N,N‐di‐p‐methoxyphenyl‐amine)9,9′spiro‐bifluorene (spiro‐OMeTAD), in order to enhance the light absorption within thin films. As is the case with spiro‐OMeTAD based solid‐state DSSC, the P3HT‐based devices improve significantly with the addition of lithium bis(trifluoromethylsulfonyl)imide salts (Li‐TFSI), although the precise role of these additives has not yet been clarified in solid‐state DSCs. Here, we present a thorough study on the effect of Li‐TFSI in P3HT based solid‐state DSSC incorporating an indolene‐based organic sensitizer termed D102. Employing ultrafast transient absorption and cw‐emission spectroscopy together with electronic measurements, we demonstrate a fine tuning of the energetic landscape of the active cell components by the local Coulomb field induced by the ions. This increases the charge transfer nature of the excited state on the dye, significantly accelerating electron injection into the TiO₂. We demonstrate that this ionic influence on the excited state energy is the primary reason for enhanced charge generation with the addition of ionic additives. The deepening of the relative position of the TiO₂ conduction band, which has previously been thought to be the cause for enhanced charge generation in dye sensitized solar cells with the addition of lithium salts, appears to be of minor importance in this system.     

Reduction of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine by zerovalent iron: product distribution

RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) and HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine) are cyclic nitramines ((CH2NNO2)n; n = 3 or 4, respectively) widely used as energetic chemicals. Their extensive use led to wide environmental contamination. In contrast to RDX, HMX tends to accumulate in soils due to its unique recalcitrance. In the present study, we investigated the potential of zerovalent iron (ZVI) to transform HMX under anoxic conditions. HMX underwent a rapid transformation when added in well-mixed anoxic ZVI-H2O batch systems to ultimately produce formaldehyde (HCHO), ammonium (NH4+), hydrazine (NH2NH2), and nitrous oxide (N2O). Time course experiments showed that the mechanism of HMX transformation occurred through at least two initial reactions. One reaction involved the sequential reduction of N-NO2 groups to the five nitroso products (1NO-HMX, cis-2NO-HMX, trans-2NO-HMX, 3NO-HMX, and 4NO-HMX). Another implied ring cleavage from either HMX or 1NO-HMX as demonstrated by the observation of methylenedinitramine (NH(NO2)CH2NH(NO2)) and another intermediate that was tentatively identified as (NH(NO2)CH2N(NO)CH2NH-(NO2)) or its isomer (NH(NO)CH2N(NO2)CH2NH(NO2)). This is the first study that demonstrates transformation of HMX by ZVI to significant amounts of NH2NH2 and HCHO. Both toxic products seemed to persist under reductive conditions, thereby suggesting that the ultimate fate of these chemicals, particularly hydrazine, should be understood prior to using zerovalent iron to remediate cyclic nitramines.     

Diversity of stress tolerance in Lactobacillus plantarum, Lactobacillus pentosus and Lactobacillus paraplantarum: A multivariate screening study

Sixty-three strains of the taxonomically related species Lactobacillus plantarum subsp. plantarum, L. plantarum subsp. argentoratensis, L. paraplantarum and L. pentosus isolated from sourdoughs and other food and non-food sources and 14 strains of other members of the genus Lactobacillus were screened for their tolerance of acid, alkaline, heat, oxidative, osmotic, detergent and starvation stresses in order to evaluate the diversity of stress response. Most strains of the L. plantarum group were highly tolerant of acid, alkaline and osmotic stress and highly sensitive to detergent stress, while a larger diversity was found for other stress. Multivariate analysis allowed grouping the strains in clusters with similar response patterns. Stress response patterns in the L. plantarum group were similar to those of species of the L. casei/L. paracasei group but clearly different from those of other mesophilic Lactobacillus. No relationship was found between grouping obtained on the basis of stress response patterns and by genotypic fingerprinting (rep-PCR), nor with the taxonomic position or isolation source of the strains. Further experiments with selected strains showed that exponential phase cells were generally but not always more sensitive than stationary phase cells. The ability to grow under stressful conditions showed a slightly better correlation with the ecological conditions prevailing in the isolation niches of the strains.This study will be the basis for further investigations to identify and exploit the basis of diversity in the stress response of lactic acid bacteria.     

Maximum Residue Levels of Veterinary Medicines in Relation to Food Safety: European Community Legislation and Ethical Aspects

Residues of veterinary medicinal products, as defined by the European Union, are “pharmacologically active substances (whether active principles, excipients or degradation products) and their metabolites which remain in foodstuffs obtained from animals to which the veterinary medicinal product in question has been administered”. The policy for Maximum Residue Limit (MRL) setting is focused on a high protection level for the consumer. MRL can be set when risk assessment shows no risk for the consumer. An MRL is the maximum concentration of residue following administration of a veterinary medicine which is legally permitted or acceptable in food under the laws of the EU. The responsibility for keeping residues under the MRL lies with veterinarians and farmers, using licensed animal medicines. Violative residues of veterinary medicines can occur as a result of improper use of a licensed product or through the illegal use of an unlicensed substance. Consequently, it became clear that prudent use of not only antimicrobials used for treatment and prevention of disease but also those used for growth promotion (e.g. β-agonists or steroid hormones) in farm animals is an integral part of good veterinary practice. In the following an overview of the European Community legislation on the studies required for residues is given. Ethical aspects are also considered. Received: March 6, 2008; accepted: March 17, 2008     

The impact of chief executive officer personality on top management team dynamics: One mechanism by which leadership affects organizational performance.

This article explores 1 mechanism by which leader personality affects organizational performance. The authors hypothesized and tested the effects of leader personality on the group dynamics of the top management team (TMT) and of TMT dynamics on organizational performance. To test their hypotheses, the authors used the group dynamics q-sort method, which is designed to permit rigorous, quantitative comparisons of data derived from qualitative sources. Results from independent observations of chief executive officer (CEO) personality and TMT dynamics for 17 CEOs supported the authors' hypothesized relationships both between CEO personality and TMT group dynamics and between TMT dynamics and organizational performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)