Relative involvement of protein kinase C and of the estrogen receptor in the cytotoxic action of a population of triphenylethylenes on MCF7 cells as revealed by correspondence factorial (CF) analysis

A multivariate statistical method, correspondence factorial (CF) analysis, was used to examine the correlations among the protein binding and cell proliferation effects of a series of 36 di- and triphenylethylenes (DPEs and TPEs). The analysis was applied to a study which measured their competition for estradiol binding to cytosol estrogen receptor (ER), their influence on protein kinase C (PKC) activity under different conditions of enzyme activation, their ability to promote the growth of a breast cancer cell line and to inhibit growth at high concentrations (cytotoxicity). The CF analysis revealed several levels of correlation. First, it distinguished those molecules within the population that stimulated rather than inhibited PKC activity. Second, it made apparent a strong correlation between cytotoxicity and inhibition of Ca++ and phosphatidylserine-dependent PKC activity, which was most marked when the enzyme had been activated by diacylglycerol indicating that PKC inhibition under physiological conditions might contribute to the overall cytotoxicity of these compounds. Third, a lower level of correlation was established between competition for ER binding and cytotoxicity. Taken together, the results suggest that MCF7 cells might be most sensitive to a cytotoxic effect of TPEs (via PKC and other targets) when they at the same time decrease estrogen-stimulated proliferation via an ER-mediated antiestrogenic effect.     

Electrochemical chlorination of azulene derivatives: Insight into the mechanism of anodic oxidative chlorination

The cyclic voltammetry behavior of a series of five 1-substituted azulenes has been investigated as well as the electrochemical chlorination of these compounds. In the case of azulene compounds containing electron withdrawing groups which have higher oxidation potentials than that of the chloride ion, the electrochemical chlorination led usually to 3-chloro derivatives. The electrochemical chlorination fails for azulenes with lower oxidation potentials. Additionally some polyhalogenated compounds were obtained by controlled potential electrolyses. The paper also discusses the reaction mechanism of the electrochemical halogenation of 1-substituted azulenes.     

Harmonization of renewable electricity feed-in laws in the European Union

This paper focuses on the harmonization of feed-in laws in the European Union as a support mechanism for the promotion of renewable electricity. In particular, it proposes a methodology for harmonization based on a feed-in law with a modular and transparent premium for renewable electricity producers. This premium considers technology costs, some grid services, political incentives and national priorities. The proposed approach includes flexibility mechanisms to update and revise premiums, to avoid windfall profits for producers, and to share technology innovation benefits with electricity consumers while maintaining incentives for innovation. Our approach is based on the review of the main features of the German and Spanish feed-in laws, and takes into account other necessary considerations for harmonization, such as grid access, funding, definitions and standards, ownership of rights derived from renewables, and exceptions for small non-commercial producers and energy-intensive industries.     

Evidence for a Negative Correlation between Human Reactive Enamine-Imine Intermediate Deaminase A (RIDA) Activity and Cell Proliferation Rate: Role of Lysine Succinylation of RIDA

Reactive intermediate deaminase (Rid) proteins are enzymes conserved in all domains of life. UK114, a mammalian member of RidA subfamily, has been firstly identified as a component of liver perchloric acid-soluble proteins (L-PSP). Although still poorly defined, several functions have been attributed to the mammalian protein UK114/RIDA, including the reactive intermediate deamination activity. The expression of UK114/RIDA has been observed in some tumors, arousing interest in this protein as an evaluable tumor marker. However, other studies reported a negative correlation between UK114/RIDA expression, tumor differentiation degree and cell proliferation. This work addressed the question of UK114/RIDA expression in human non-tumor HEK293 cell lines and in some human tumor cell lines. Here we reported that human RIDA (hRIDA) was expressed in all the analyzed cell line and subjected to lysine (K-)succinylation. In HEK293, hRIDA K-succinylation was negatively correlated to the cell proliferation rate and was under the control of SIRT5. Moreover, K-succinylation clearly altered hRIDA quantification by immunoblotting, explaining, at least in part, some discrepancies about RIDA expression reported in previous studies. We found that hRIDA was able to deaminate reactive enamine-imine intermediates and that K-succinylation drastically reduced deaminase activity. As predicted by in silico analysis, the observed reduction of deaminase activity has been related to the drastic alterations of hRIDA structure inferred by K-succinylation. The role of hRIDA and the importance of its K-succinylation in cell metabolism, especially in cancer biology, have been discussed.     

A Methionine Chemical Shift Based Order Parameter Characterizing Global Protein Dynamics

Coupling of side chain dynamics over long distances is an important component of allostery. Methionine side chains show the largest intrinsic flexibility among methyl-containing residues but the actual degree of conformational averaging depends on the proximity and mobility of neighboring residues. The ¹³C NMR chemical shifts of the methyl groups of methionine residues located at long distances in the same protein show a similar scaling with respect to the values predicted from the static X-ray structure by quantum methods. This results in a good linear correlation between calculated and observed chemical shifts. The slope is protein dependent and ranges from zero for the highly flexible calmodulin to 0.7 for the much more rigid calcineurin catalytic domain. The linear correlation is indicative of a similar level of side-chain conformational averaging over long distances, and the slope of the correlation line can be interpreted as an order parameter of the global side-chain flexibility.     

Effects of allelochemicals on plant respiration and oxygen isotope fractionation by the alternative oxidase

The goal of this investigation was to determine the effects of allelochemicals on plant respiration that thereby may be responsible for their role in growth inhibition. We have tested the effects of juglone, quercetin, cinnamic acid, and-pinene on respiration rates, and electron partitioning through the cytochrome and alternative respiratory pathways, by measuring on-line oxygen consumption and oxygen isotope fractionation in soybean cotyledon tissue. Cinnamic acid and-pinene decreased the oxygen consumption rate and increased the relative partitioning of electron transport to the alternative pathway. Possible biochemical mechanisms of these effects are discussed.     

Discovering social structures of local influence by using tweetStimuli

Information diffusion in large-scale networks has been studied to identify the users influence. The influence has been targeted as a key feature either to reach large populations or influencing public opinion. Through the use of micro-blogs, such as Twitter, global influencers have been identified and ranked based on message propagation (retweets). In this paper, a new application is presented, which allows to find first and classify then the local influence on Twitter: who have influenced you and who have been influenced by you. Until now, social structures of tweets’ original authors that have been either retweeted or marked as favourites are unobservable. Throughout this application, these structures can be discovered and they reveal the existence of communities formed by users of similar profile (that are connected among them) interrelated with other similar profile users’ communities.     

Solving weighted CSPs with meta-constraints by reformulation into satisfiability modulo theories

We introduce WSimply, a new framework for modelling and solving Weighted Constraint Satisfaction Problems (WCSP) using Satisfiability Modulo Theories (SMT) technology. In contrast to other well-known approaches designed for extensional representation of goods or no-goods, and with few declarative facilities, our approach aims to follow an intensional and declarative syntax style. In addition, our language has built-in support for some meta-constraints, such as priority and homogeneity, which allows the user to easily specify rich requirements on the desired solutions, such as preferences and fairness. We propose two alternative strategies for solving these WCSP instances using SMT. The first is the reformulation into Weighted SMT (WSMT) and the application of satisfiability test based algorithms from recent contributions in the Weighted Maximum Satisfiability field. The second one is the reformulation into an operation research-like style which involves an optimisation variable or objective function and the application of optimisation SMT solvers. We present experimental results of two well-known problems: the Nurse Rostering Problem (NRP) and a variant of the Balanced Academic Curriculum Problem (BACP), and provide some insights into the impact of the addition of meta-constraints on the quality of the solutions and the solving time.