Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.     

Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol–ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.     

A new short-path distillation system applied to the reduction of cholesterol in butter and lard

A molecular distillation plant, built particularly to increase the separation efficiency and to obtain safer working conditions, was tested to remove cholesterol from anhydrous butter and lard. A preliminary experiment was carried out with butter to evaluate the fractionation obtained at temperatures between 190 and 250°C and residual pressures between 10⁻³ and 10⁻⁴ torr. A second experiment was carried out at 185°C and at the maximum operational vacuum, evaluating the fractionation achieved within a time scale between 30 and 180 min. Cholesterol was almost completely removed during the second hour with minimal loss of low-molecular weight triglycerides. An experiment was carried out with lard at 250°C and maximum achievable operational vacuum (10⁻⁴ Torr), lasting approximately 6 h, and cholesterol was removed almost completely during the second hour without significant modifications in the triglyceride composition. This situation remained constant throughout the duration of the test.     

Ion‐exchange resins. II. Acrylamide crosslinked copolymers as precursors for some ion exchangers

Crosslinked copolymers of acrylamide (AA) and ethylacrylate and some ion exchangers derived from them containing either primary amine groups, obtained by the Hofmann degradation of the amide groups, or carboxylic groups, obtained by the alkaline hydrolysis of the ester groups, were studied. Divinylbenzene and N,N′‐methylenebisacrylamide were used as crosslinkers. The starting copolymers and the corresponding ion exchangers were characterized by IR spectroscopy, swelling behavior, and thermogravimetric analysis. The ion‐exchanger properties were correlated with the crosslinker nature and the chemical reactions performed on the AA copolymers. The average molecular weight between two crosslinks, determined from the swelling data in water, was compared with that calculated on the basis of the copolymerization stoichiometry only for the carboxylic cation exchangers. In this way, the preservation of the crosslink density after the hydrolysis was revealed. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 2701–2707, 2003     

SIVR epidemic model with stochastic perturbation

We propose a stochastic disease model where vaccination is included and such that the immunity is permanent. The existence, uniqueness, and positivity of the solution and the stability of the disease-free equilibrium are studied.     

Effect of low‐temperature plasma and chitosan treatment on wool dyeing with Acid Red 27

This study examines in detail the influence of low‐temperature plasma and biopolymer chitosan treatments on wool dyeability. Wool knitted fabrics were treated and characterized by whiteness and shrink‐resistance measurements. Surface modification was assessed by contact‐angle measurements of human hair fibers, which were used as a model to study the wetting properties of the treated wool knitted fabrics. The dyeing behavior was assessed from the diffusion mechanism point of view. The dyeing kinetics were measured at two different pHs (4.2 and 6.5) and three different temperatures (60, 85, and 100°C) to gain information about the contribution of the surface modification treatment to the dyeing mechanism. The exhaustion and reflectance data were compared, and the apparent diffusion coefficients were calculated. On the basis of the obtained results, a model for the dyeing mechanism of the chitosan treated wool was proposed. When treated with chitosan, the polymer sheath spread on the surface of the fibers acted as a predominant dyeing site in very short dyeing times, thus interacting with the dye and in later stages imparting the dye to the wool fiber. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 97: 2204–2214, 2005     

Ensemble-based noise detection: noise ranking and visual performance evaluation

Noise filtering is most frequently used in data preprocessing to improve the accuracy of induced classifiers. The focus of this work is different: we aim at detecting noisy instances for improved data understanding, data cleaning and outlier identification. The paper is composed of three parts. The first part presents an ensemble-based noise ranking methodology for explicit noise and outlier identification, named Noise- Rank, which was successfully applied to a real-life medical problem as proven in domain expert evaluation. The second part is concerned with quantitative performance evaluation of noise detection algorithms on data with randomly injected noise. A methodology for visual performance evaluation of noise detection algorithms in the precision-recall space, named Viper, is presented and compared to standard evaluation practice. The third part presents the implementation of the NoiseRank and Viper methodologies in a web-based platform for composition and execution of data mining workflows. This implementation allows public accessibility of the developed approaches, repeatability and sharing of the presented experiments as well as the inclusion of web services enabling to incorporate new noise detection algorithms into the proposed noise detection and performance evaluation workflows.     

Solid solutions of C3A---Na2O in C12A7

This paper reports upon the research into the influence of sodium ions on C₁₂A₇. The actual research work consisted in synthesizing C₁₂A₇, treated with the sodium ions as Na₂CO₃, within the sodium concentration range of up to 25% Na₂O by weight in C₁₂A₇. The resultant combinations have been identified by the X-ray analysis, the infra-red spectroscopy and the quantitative chemical analysis.

The identification procedure together with the analysis of free CaO content in the products of C₁₂A₇ sodium synthesis gave evidence that sodium which is introduced into the researched amount of C₁₂A₇ up to 10% Na₂O by weight, contributes to the formation of the ever increasing phase of the solid solutions of Na₂O in C₃A. The continued increase of the sodium volume ( 15% Na₂O by weight ) makes it resolve gradually into sodium aluminate β -NA and free CaO.     

Effect of olive paste kneading process time on the overall quality of virgin olive oil

The influence of the olive paste malaxation time on the composition and the industrial output of oil was investigated. To this purpose, three Italian olive varieties (Leccino, Dritta, Caroleo) were processed with a centrifugal system for six malaxation periods (0, 15, 30, 45, 60 and 75 min). The concentrations of the majority of the oil constituents changed during the malaxation. However, these changes were not significant for all of them: the contents of β‐carotene, the major xanthophylls, chlorophylls a and b, pheophytins a and b in the oils increased progressively with increasing malaxing times, whereas the contents of simple and hydrolysable phenols (secoiridoid derivatives), o‐diphenols and total phenols decreased. A significant increase in total volatiles and green volatiles of the lipoxygenase cascade (C₆ aldehydes, C₆ alcohols, C₅ alcohols and C₅ carbonyls) was detected. An opposite trend was observed for the green C₆ esters. As a result, the global analytical quality, flavour, aroma and shelf‐life of the oils were negatively affected. The oil yield increased substantially up to 45 min of paste malaxation times. Beyond 60 min, the yields tended to decrease.     

Stereospecific distribution of fatty acids in triacylglycerols of olive oils

The positional distribution of fatty acids (FA) in triacylglycerols (TAG) of 47 virgin olive oils from diverse cultivars grown in distinct areas of North‐Eastern Italy was studied. Few data were previously available on oils from these geographical areas. The effects of climatic and geographical conditions on the stereospecific distribution of TAG in olive oil were confirmed. Moreover, the results of the stereospecific analysis were used to evaluate the preferential esterification position of each FA on the basis of the degree of unsaturation and the chain length. The data of the stereospecific analysis of olive oil TAG can contribute to the determination of the selectivity of olive fruit acyltransferases for distinct FA.