Adenosine Signaling in Mast Cells and Allergic Diseases

Adenosine is a nucleoside involved in the pathogenesis of allergic diseases. Its effects are mediated through its binding to G protein-coupled receptors: A1, A2a, A2b and A3. The receptors differ in the type of G protein they recruit, in the effect on adenylyl cyclase (AC) activity and the downstream signaling pathway triggered. Adenosine can produce both an enhancement and an inhibition of mast cell degranulation, indicating that adenosine effects on these receptors is controversial and remains to be clarified. Depending on the study model, A1, A2b, and A3 receptors have shown anti- or pro-inflammatory activity. However, most studies reported an anti-inflammatory activity of A2a receptor. The precise knowledge of the adenosine mechanism of action may allow to develop more efficient therapies for allergic diseases by using selective agonist and antagonist against specific receptor subtypes.     

The Casein Kinase 2‐Dependent Phosphorylation of NS5A Domain 3 from Hepatitis C Virus Followed by Time‐Resolved NMR Spectroscopy

Hepatitis C virus (HCV) chronically affects millions of individuals worldwide. The HCV nonstructural protein 5A (NS5A) plays a critical role in the viral assembly pathway. Domain 3 (D3) of NS5A is an unstructured polypeptide responsible for the interaction with the core particle assembly structure. Casein kinase 2 (CK2) phosphorylates NS5A‐D3 at multiple sites that have mostly been predicted and only observed indirectly. In order to identify the CK2‐dependent phosphorylation sites, we monitored the reaction between NS5A‐D3 and CK2 in vitro by time‐resolved NMR. We unambiguously identified four serine residues as substrates of CK2. The apparent rate constant for each site was determined from the reaction curves. Ser408 was quickly phosphorylated, whereas the three other serine residues reacted more slowly. These results provide a starting point from which to elucidate the role of phosphorylation in the mechanisms of viral assembly—and in the modulation of the viral activity—at the molecular level.     

Tribocorrosion and corrosion behavior of stainless steel coated with DLC films in ethanol with different concentrations of water

There has been a recent increase in both the production and consumption of ethanol due to the numerous environmental advantages that it offers, such as the fact that it can be produced from a variety of renewable materials, for instance corn and cellulose, or it can be obtained from sugarcane bagasse and biomass (2nd and 3rd generation ethanol). The result of this is that nowadays ethanol is widely seen as the dominant biofuel – or as a blend component in gasoline or pure fuel - in many countries.However, one disadvantage of the use of ethanol is the high corrosive behavior that occurs when its hygroscopic properties are exposed to a large number of materials. Xiaoyuan Lou and Preet Singh showed that the increase of water concentration in ethanol induces pitting and metal loss. Diamond-Like Carbon (DLC) films may be a solution to this problem due to the fact that they can be deposited inside tubes, offer good protection levels against corrosion, and reduce the friction coefficient and wear.This paper shows the tribocorrosion and corrosion studies of DLC films deposited on stainless steel grade 304 (SS304) substrates in order to gauge its appropriateness usage in the construction of pipelines and fuel storage tanks. The surface morphology was analyzed before and after 14 days of immersion. The tribocorrosion, friction coefficient, and wear rate were studied in ethanol to see the effects of water concentration. The films showed good adherence to the substrates. Corrosion and tribocorrosion results showed that for bare Stainless Steel 304 the increase of the water content increases the corrosion and the friction coefficient. DLC coated samples presented few points of delamination, and the friction coefficient and open circuit potentials were very low compared with the bare sample which was water concentration independent.     

trans Fatty Acids in Colostrum,Mature Milk and Diet of Lactating Adolescents

The purpose of this study was to investigate the trans fatty acids (TFA) content and distribution in colostrum, mature milk, and diet of adolescent mothers, after TFA declaration in food labels became mandatory in Brazil. Participants were healthy adolescents (n 54, 15–19 years, 1–90 days postpartum) practicing exclusive breastfeeding. Milk samples were collected 3 days after delivery (colostrum) and in the third month postpartum (mature milk) by hand expression. The fatty acid composition of the milk samples was determined by gas chromatography. TFA intake corresponded to 1.23 % of total energy value. Total 18:2 TFA accounted for less than 0.5 % of the energy intake. The amount of total 18:1 TFA (mean ± SEM) was 1.9 % ± 0.14 in colostrum and 1.5 % ± 0.2 in mature milk. The total content of n‐3 PUFA was inversely correlated with the total content of 18:1 TFA in colostrum. Both in colostrum and in mature milk, vaccenic acid (11t‐18:1) was found to be the most abundant 18:1 trans isomer, followed by elaidic acid (9t‐18:1), whereas rumenic acid (9c,11t‐18:2 CLA) was the predominant 18:2 trans isomer. In conclusion, the levels of TFA of industrial sources found in the mother's diet and breast milk (colostrum and mature milk) showed a decrease in relation to those observed in studies conducted prior to the TFA labeling resolution in Brazil. However, the current low intake levels of n‐3 LCPUFA and DHA content in the milk of lactating adolescents may be insufficient for supporting adequate neurological development of the infants.     

Designing Dual Transglutaminase 2/Histone Deacetylase Inhibitors Effective at Halting Neuronal Death

In recent years there has been a clear consensus that neurodegenerative conditions can be better treated through concurrent modulation of different targets. Herein we report that combined inhibition of transglutaminase 2 (TG2) and histone deacetylases (HDACs) synergistically protects against toxic stimuli mediated by glutamate. Based on these findings, we designed and synthesized a series of novel dual TG2–HDAC binding agents. Compound 3 [(E)‐N‐hydroxy‐5‐(3‐(4‐(3‐oxo‐3‐(pyridin‐3‐yl)prop‐1‐en‐1‐yl)phenyl)thioureido)pentanamide] emerged as the most interesting of the series, being able to inhibit TG2 and HDACs both in vitro (TG2 IC₅₀=13.3±1.5 μm , HDAC1 IC₅₀=3.38±0.14 μm , HDAC6 IC₅₀=4.10±0.13 μm ) and in cell‐based assays. Furthermore, compound 3 does not exert any toxic effects in cortical neurons up to 50 μm and protects neurons against toxic insults induced by glutamate (5 mm ) with an EC₅₀ value of 3.7±0.5 μm .     

Development and evaluation of a virtual campus on Second Life: The case of SecondDMI

Video games and new communication metaphors are quickly changing today’s young people habits. Considering the actual e-learning scenarios, embedded in a fully technological enabled environment it is crucial to take advantage of this kind of capabilities to let learning process gain best results.     

Assessing the usability of a visual tool for the definition of e-learning processes

In this paper, we present a usability study aiming at assessing a visual language-based tool for developing adaptive e-learning processes. The tool implements the adaptive self-consistent learning object SET (ASCLO-S) visual language, a special case of flow diagrams, to be used by instructional designers to define classes of learners through stereotypes and to specify the more suited adaptive learning process for each class of learners. The usability study is based on the combined use of two techniques: a questionnaire-based survey and an empirical analysis. The survey has been used to achieve feedbacks from the subjects’ point of view. In particular, it has been useful to capture the perceived usability of the subjects. The outcomes show that both the proposed visual notation and the system prototype are suitable for instructional designers with or without experience on the computer usage and on tools for defining e-learning processes. This result is further confirmed by the empirical analysis we carried out by analysing the correlation between the effort to develop adaptive e-learning processes and some measures suitable defined for those processes. Indeed, the empirical analysis revealed that the effort required to model e-learning processes is not influenced by the experience of the instructional designer with the use of e-learning tools, but it only depends on the size of the developed process.     

How many do you see? The use of nonspoken representations in first-grade mathematics lessons.

Not all relevant instructional information comes in the form of spoken words. In the present study, the authors examine multiple modalities of nonspoken forms of representation—specifically gestures, pictures, objects, and writing—used by 3 teachers in 3 yrs of 1st-grade math lessons. Teachers frequently used visually based modalities of representation and tended to produce combinations of representational forms rather than isolated representations. There were individual differences in their preference for representation types. Teachers used representations to accompany important spoken terms and to respond to student confusion. With nonspoken representations, teachers conveyed information critical to the explanation of mathematical concepts. Students must attend to the visual as well as vocal means of expressing information to gain access to all of the information presented in mathematics lessons. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The statistical analysis of data from small groups.

The authors elaborate the complications and the opportunities inherent in the statistical analysis of small-group data. They begin by discussing nonindependence of group members' scores and then consider standard methods for the analysis of small-group data and determine that these methods do not take into account this nonindependence. A new method is proposed that uses multilevel modeling and allows for negative nonindependence and mutual influence. Finally, the complications of interactions, different group sizes, and differential effects are considered. The authors strongly urge that the analysis model of data from small-group studies should mirror the psychological processes that generate those data. (PsycINFO Database Record (c) 2010 APA, all rights reserved)