A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer.     

Monitoring a mixed starter of Hanseniaspora vineae-Saccharomyces cerevisiae in natural must: impact on 2-phenylethyl acetate production

The effect of simultaneous or sequential inoculation of Hanseniaspora vineae CECT 1471 and Saccharomyces cerevisiae T73 in non-sterile must on 2-phenylethyl acetate production has been examined. In both treatments tested, no significant differences in Saccharomyces yeast growth were found, whereas non-Saccharomyces yeast growth was significantly different during all days of fermentation. Independently of the type of inoculation, S. cerevisiae was the predominant species from day 3 till the end of the fermentation. The dynamics of indigenous and inoculated yeast populations showed H. vineae to be the predominant non-Saccharomyces species at the beginning of fermentation in sequentially inoculated wines, whereas the simultaneous inoculation of S. cerevisiae did not permit any non-Saccharomyces species to become predominant. Differences found in non-Saccharomyces yeast growth in both fermentations influenced the analytical profiles of final wines and specifically 2-phenylethyl acetate concentration which was two-fold increased in sequentially inoculated wines in comparison to those co-inoculated. In conclusion we have shown that H. vineae inoculated as part of a sequential mixed starter is able to compete with native yeasts present in non-sterile must and modify the wine aroma profile.     

New Insights to Clathrin and Adaptor Protein 2 for the Design and Development of Therapeutic Strategies

The Amyloid Precursor Protein (APP) has been extensively studied for its role as the precursor of the β-amyloid protein (Aβ) in Alzheimer’s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that the Y₆₈₂ mutation in the ₆₈₂YENPTY₆₈₇ domain of APP affects its binding to specific adaptor proteins and leads to its anomalous trafficking, to defects in the autophagy machinery and to neuronal degeneration. In order to identify adaptors that influence APP function, we performed pull-down experiments followed by quantitative mass spectrometry (MS) on hippocampal tissue extracts of three month-old mice incubated with either the ₆₈₂YENPTY₆₈₇ peptide, its mutated form, ₆₈₂GENPTY₆₈₇ or its phosphorylated form, ₆₈₂pYENPTY₆₈₇. Our experiments resulted in the identification of two proteins involved in APP internalization and trafficking: Clathrin heavy chain (hc) and its Adaptor Protein 2 (AP-2). Overall our results consolidate and refine the importance of Y₆₈₂ in APP normal functions from an animal model of premature aging and dementia. Additionally, they open the perspective to consider Clathrin hc and AP-2 as potential targets for the design and development of new therapeutic strategies.     

Effects of thermal annealing on the optical characteristics of k -na + waveguides

We present a systematic study of the changes induced in the refractive-index profile of different sets of K -Na + ion-exchanged waveguides on soda-lime and BK7 substrates because of thermal annealing in the presence or absence of salt vapors. The concentration of potassium is recovered by secondary ion mass spectrometry, and the propagation losses are measured by means of the three-prism configuration.     

A parametric study of AlN thin films grown by pulsed laser deposition

High quality AlN thin films were grown at 200–450°C on sapphire substrates by laser ablation of Al targets in nitrogen reactive atmosphere. The nitrogen pressure was varied between 10⁻³ and 10⁻¹ mbar. The reactive gas pressure during irradiation and the temperature of the substrate were found to essentially influence the quality of the layers. X-ray diffraction analysis evidenced the formation of highly orientated layers for a very restrictive set of parameters. Other analysis techniques, like X-ray photoelectron spectroscopy, secondary ion mass spectroscopy, optical transmission spectroscopy have been used to evidence the good stoichiometry and purity of the films. The characteristics of these films were compared with those of AlN thin films deposited in similar experimental conditions, on Si (100) and Si (111) substrates.     

Nicotine as a conditioned stimulus: Impact of attention-deficit/hyperactivity disorder medications.

People diagnosed with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk to start smoking and have greater difficulty quitting. Nicotine, one of the principal addictive components of tobacco smoke, functioned as a conditioned stimulus (CS) for intermittent sucrose delivery in a Pavlovian drug discrimination task with rats. This study compared the ability of commonly prescribed ADHD medications (i.e., methylphenidate, atomoxetine, and bupropion) and additional dopamine reuptake inhibitors (i.e., cocaine and GBR 12909) to substitute for the CS effects of nicotine. Atomoxetine was also used to antagonize these CS effects. Rats acquired the discrimination as evidenced by increased dipper entries in nicotine (0.2 mg base/kg) sessions as compared with saline sessions. Nicotine generalization was dose dependent. Bupropion (10 and 20 mg/kg), methylphenidate (10 mg/kg), and cocaine (5 and 10 mg/kg) partially substituted for the 0.2 mg/kg nicotine CS. Atomoxetine did not substitute for the nicotine CS; however, atomoxetine (1 to 10 mg/kg) partially blocked nicotine's CS effects. These results suggest that atomoxetine, bupropion, and/or methylphenidate may be effective treatments for people diagnosed with ADHD and addicted to nicotine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pattern Perturbation Method for Multicanonical Monte Carlo Simulations in Optical Communications

In this letter, we present a novel method to efficiently account for pattern dependence in the bit-error-ratio (BER) estimation of an optical communication system through multi-canonical Monte Carlo (MMC) simulations. The proposed method considers the transmitted pattern as random, extending the MMC random-walk to the overall state space comprising noise and pattern. The resulting complexity is only linear in the intersymbol interference length, allowing us to account for long pattern dependence in a feasible computational time. The accuracy of the method is confirmed by the agreement of simulations with the exact probability density functions and BER values evaluated through the Karhunen-Loeve series expansion method.     

Peculiar aspects of nanocrystal memory cells: data and extrapolations

Nanocrystal memory cell are a promising candidate for the scaling of nonvolatile memories in which the conventional floating gate is replaced by an array of nanocrystals. The aim of this paper is to present the results of a thorough investigation of the possibilities and the limitations of such new memory cell. In particular, we focus on devices characterized by a very thin tunnel oxide layer and by silicon nanocrystals formed by chemical vapor deposition. The direct tunneling of the electrons through the tunnel oxide, their storage into the silicon nanocrystals, and furthermore, retention, endurance, and drain turn-on effects, well-known issues for nonvolatile memories, are all investigated. The cell can be also programmed by channel hot electron injection, allowing the possibility to multibit storage. The suppression of the drain turn-on and the possibility of using this cell for multibit storage give us a clear evidence of the distributed nature of the charge storage.     

Use of a toasted durum whole meal in the production of a traditional Italian pasta: chemical, mechanical, sensory and image analyses

The characterisation of traditional Italian pasta obtained by mixing amounts of toasted whole meal with re-milled semolina and other ingredients was obtained by means of physico-chemical, rheological, mechanical, sensory and image analyses. The toasted meal showed higher ash, fibre and protein contents than re-milled semolina. The replacement of percentages of re-milled semolina with the toasted meal and soft flour increased tenacity and decreased extensibility and strength, making the dough less suitable for pasta-making. The P / L values were indices of high starch damage. The replacement of part of re-milled semolina and water with toasted whole wheat meal, soft flour and eggs increased the optimal cooking time and the amount of water absorbed during cooking but made the other cooking parameters worse. The image analysis provided evidence of the changes induced by the use of toasted wholemeal, soft flour and eggs in the microscopic structure of pasta protein and starch.