Preparation and Nc/T plots of un-crystallized Nafion 1100 and semi-crystalline Nafion 1000

The last advances on the application of INCA (Ionomer Nc Analysis) methodology for a better understanding of perfluorinated ionomers are reported and discussed. It was found that INCA is a very suitable technique for the determination of the melting temperature (Tm) of un-crystallized and semi-crystalline perfluorinated ionomers. Furthermore, for these determinations, it is even more precise than dynamic mechanical analysis, a method essentially developed for polymers in which the water-uptake is negligible. Of interest, it is the information that INCA methodology gives on the phenomenon of the water-uptake memory of perfluorinated ionomers.     

Applications of Isothermal Titration Calorimetry in Biophysical Studies of G-quadruplexes

G-quadruplexes are higher-order nucleic acids structures formed by G-rich sequences that are stabilized by tetrads of hydrogen-bonded guanine bases. Recently, there has been growing interest in the study of G-quadruplexes because of their possible involvement in many biological processes. Isothermal titration calorimetry (ITC) has been proven to be a useful tool to study the energetic aspects of G-quadruplex interactions. Particularly, ITC has been applied many times to determine the thermodynamic properties of drug-quadruplex interactions to screening among various drugs and to address drug design. In the present review, we will focus on the ITC studies of G-quadruplex structures and their interaction with proteins and drugs and the most significant results will be discussed.     

Executive functioning, irritability, and alcohol-related aggression.

The purpose of this investigation was to examine (a) whether irritability mediates the relation between executive functioning (EF) and alcohol-related aggression and (b) whether the alcohol-aggression relation is better explained by the interactive effects of EF and irritability above and beyond the effects of either variable alone. EF was measured using seven well-established neuropsychological tests. Irritability was assessed with the Caprara Irritability Scale. Participants were 313 male and female social drinkers between 21 and 35 years of age. Following the consumption of an alcohol or a placebo beverage, participants were tested on a laboratory aggression task in which electric shocks were given to and received from a fictitious opponent under the guise of a competitive reaction-time task. Aggression was operationalized as the shock intensities administered to the fictitious opponent. Results indicated that irritability successfully mediated the relation between EF and intoxicated aggression for men only. Despite the fact that irritability and EF both independently moderated the alcohol-aggression relation in previous studies, no significant interaction for their combined effect was detected here. The findings are discussed, in part, within a cognitive neoassociationistic framework for aggressive behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Executive functioning and alcohol-related aggression: Reply to Weingartner (2000), Bates (2000), Lyvers (2000), Cherek (2000), and Berman (2000).

H. Weingartner (see record 2000-02949-018), M. E. Bates (see record 2000-02949-014), M. Lyvers (see record 2000-02949-017), D. R. Cherek (see record 2000-02949-016), and M. E. Berman (see record 2000-02949-015) put forth some very interesting and thought-provoking commentaries on the author's executive functioning framework for alcohol-related aggression (P. R. Giancola; see record 2000-02949-013). Many of their comments raised very important questions such as how executive functioning should be defined and conceptualized. Specifically, they asked whether executive functioning is better conceptualized as a unidimensional macroconstruct or as a set of related, yet independent, cognitive processes. Another key question was what other factors does executive functioning interact with to facilitate intoxicated aggression. Although these issues are far from being resolved, the author hopes that his article, their commentaries, and his responses will generate new research that will ultimately help to better predict and prevent alcohol-related aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Agreeableness and alcohol-related aggression: The mediating effect of trait aggressivity.

This study investigated the mediating effect of trait aggressivity on the relation between agreeableness and alcohol-related aggression in a laboratory setting. Participants were 116 healthy male social drinkers between 21 and 30 years of age. Agreeableness and trait aggressivity were measured using the Big Five Inventory and the Buss-Perry Aggression Questionnaire, respectively. Following the consumption of an alcohol or no-alcohol control beverage, participants completed a modified version of the Taylor Aggression Paradigm, in which electric shocks were received from and administered to a fictitious opponent during a competitive task. Aggression was operationalized as the proportion of the most extreme shocks delivered to the fictitious opponent under conditions of low and high provocation. Results indicated that lower levels of agreeableness were associated with higher levels of trait aggressivity. In turn, higher levels of trait aggressivity predicted extreme aggression in intoxicated, but not sober, participants under low, but not high, provocation. Findings highlight the importance of examining determinants of intoxicated aggression within a broader theoretical framework of personality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fighting the Huntington’s Disease with a G-Quadruplex-Forming Aptamer Specifically Binding to Mutant Huntingtin Protein: Biophysical Characterization,In Vitro and In Vivo Studies

A set of guanine-rich aptamers able to preferentially recognize full-length huntingtin with an expanded polyglutamine tract has been recently identified, showing high efficacy in modulating the functions of the mutated protein in a variety of cell experiments. We here report a detailed biophysical characterization of the best aptamer in the series, named MS3, proved to adopt a stable, parallel G-quadruplex structure and show high nuclease resistance in serum. Confocal microscopy experiments on HeLa and SH-SY5Y cells, as models of non-neuronal and neuronal cells, respectively, showed a rapid, dose-dependent uptake of fluorescein-labelled MS3, demonstrating its effective internalization, even in the absence of transfecting agents, with no general cytotoxicity. Then, using a well-established Drosophila melanogaster model for Huntington’s disease, which expresses the mutated form of human huntingtin, a significant improvement in the motor neuronal function in flies fed with MS3 was observed, proving the in vivo efficacy of this aptamer.     

Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.     

Social dominance mediates the association of testosterone and neurobehavioral disinhibition with risk for substance use disorder.

This investigation determined the influence of testosterone and neurobehavioral disinhibition (ND) on risk for substance use disorder (SUD). Testosterone level during puberty was hypothesized to promote social dominance associated with norm-violating behavior that, in turn, predisposes individuals to use of illicit drugs and, subsequently, SUD. Using a prospective paradigm, the authors recruited 179 boys (mean age=11.62 years, SD=0.88) and followed up when participants were ages 12-14, 16, 19, and 22. Results indicated that social dominance/norm-violating behavior (SD/NVB) at age 16 mediated the association between testosterone level (ages 12-14) and SUD (age 22). In addition, SD/NVB mediated the association between ND and SUD. These findings suggest that development of SUD is influenced by androgen-dependent and neurobehavioral processes via a social motivational style characterized by SD/NVB. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolo-Pyrimidinones Tethered with Hydrazide-Hydrazones

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compounds.     

Executive cognitive functioning, temperament, and antisocial behavior in conduct-disordered adolescent females.

The authors assessed whether low executive cognitive functioning (ECF) and a difficult temperament are related to aggressive and nonaggressive forms of antisocial behavior (ASB) in 249, 14–18-year-old, conduct-disordered females and controls. ECF was measured using neuropsychological tests; temperament was measured using the Dimensions of Temperament Survey—Revised; and ASB was assessed using psychiatric symptom counts for conduct disorder. The conduct-disordered females exhibited lower ECF capacity and a greater difficult temperament compared with the controls. The combined influence of low ECF and difficult temperament was significantly related to both forms of ASB. In comparison with low ECF, difficult temperament was more strongly related to nonaggressive ASB, whereas in comparison with difficult temperament, low ECF was more strongly related to aggressive ASB. Last, ECF mediated the relation between difficult temperament and aggressive ASB. (PsycINFO Database Record (c) 2010 APA, all rights reserved)