Design, synthesis and use of chiral pheromone-based probes to study pheromone enantiomer discrimination in the pheromone binding proteins from the gypsy moth, Lymantria dispar

The gypsy moth is a widespread and harmful pest causing extensive damage to the Canada’s forest and orchard ecosystems. It uses (+)-disparlure as a sex pheromone. Discovery of the pheromone, including its absolute configuration, has enabled monitoring of gypsy moth populations. Disparlure of low enantiopurity is not attractive to the moths and, for this reason, enantiopure (+)-disparlure has been a synthetic target for many years. To access (+)-disparlure of high enantiopurity we have used a diastereoselective nucleophilic addition reaction with the enantiopure α-chloroaldehyde (2-chlorododecanal) that yields a stereocontrolled access to the 1,2-anti chlorohydrin core. The (+)-disparlure was prepared through a series of transformations that include a Mitsunobu inversion. We have successfully completed the synthesis of (+)-disparlure in 5 steps as compared to Iwaki’s first synthesis in 12 steps and Sharpless’s widely used synthesis in 6 steps. The same approach was used to produce 18-hydroxydisparlure enantiomers, which were coupled to a linker with an alkyne moiety at the end. The alkyne was then coupled to azide-based commercial fluorescent probes, to furnish fluorescent disparlure-based probes for physical studies. The gypsy moth has two different pheromone binding proteins, LdisPBP1 and LdisPBP2. Previously, our group has addressed the enantiomer selectivity of these two PBPs and found that PBP1 binds (-)-disparlure more strongly than (+)-disparlure, while PBP2 binds (+)-disparlure more strongly. Despite several binding assays, the interaction and discrimination of gypsy moth PBPs towards disparlure enantiomers are not fully understood due to lack of binding interaction and kinetic studies, which are technically demanding, due to the hydrophobicity of the pheromone. In this thesis, we have studied the binding interaction of deuterium-labelled (+)-disparlure and (-)-disparlure with LdisPBPs by 2H NMR spectroscopy. The results from NMR studies were correlated with the results from docking simulations of (+)-disparlure and (-)-disparlure bound to one internal site and multiple external sites of LdisPBP1 and LdisPBP2. These results indicated that (+)-disparlure and (-)-disparlure adopt different conformations and orientations in the binding pockets of LdisPBP1 and LdisPBP2. Most of the reported work on PBPs focuses on the pheromone binding affinities of PBPs. However, the pheromone-PBP interactions require more than half an hour to establish equilibrium, whereas male moths respond to female pheromones in milliseconds. Therefore, the interactions between pheromones and olfactory components such as PBPs and pheromone receptors may not be under thermodynamic control. In this thesis, we aimed to provide a dynamic perspective of pheromone-PBP interactions and to link these to the functions of PBPs. We have studied thermodynamic (Kd) and kinetic properties (kon and koff) of LdisPBPs-disparlure enantiomer interaction by fluorescence binding assays and kinetic experiments using fluorophore-tagged disparlure enantiomers. The result indicated that the binding preference of disparlure enantiomers to LdisPBPs. Based on the kinetic data of LdisPBPs with fluorophore-tagged disparlure enantiomers, we propose a kinetic model that includes a two-step binding process. Each of these two steps may contribute to a different function of the LdisPBPs

Marital fertility and the changing status of women in Europe

Fertility has by now reached very low levels in all European countries, with the exception of Albania, which is in a deviating situation. Birth rates in the other countries vary between 10 and 25‰, with minimum levels in the two German republics, Luxemburg, Finland, Austria, England and Wales, Belgium and Sweden, and maximum levels in Ireland, Portugal, Spain, Rumania, Czechoslovakia and Yugoslavia

Living Arrangements and Family Networks of Older Women in Italy

Population aging in Italy is, as in many other industrialized countries, disproportionately a phenomenon associated with unmarried women, mainly widows. This paper examines the extent to which older unmarried women live alone, and the extent to which they receive help in everyday tasks from others outside their households, using data from a large Italian household sample survey conducted in 1983. Older women can either live alone or with others, and may or may not receive external help in either case; thus there are four distinct combinations of outcomes analyzed. In both descriptive, bivariate analysis and a multivariate model of the outcomes we find pronounced differences in behavior according to region of residence, educational level, age, degree of disability, work experience and pension receipt. The findings indicate the importance of family as a source of help and/or coresidence in situations of need

The gRASs Is Greener: Potential New Therapies in Lung Cancer with Acquired Resistance to KRASG12C Inhibitors

Summary: Inhibitors of KRASG12C that bind the target in its inactive conformation and lock it in off-mode have shown early signs of clinical activity in patients with KRASG12C-mutant lung cancer, but responses tend to be short-lived and invariably prelude the development of acquired resistance through largely unexplored mechanisms. A new study describes the emergence of RAS–MAPK heterogeneous subclonal alterations in a patient relapsed on a KRASG12C inactive-state inhibitor and identifies a novel KRASY96D-resistant variant that is druggable by a next-generation compound capable of associating with KRASG12C in its active configuration

Giftedness and gifted education: A systematic literature review.

The present study aims to discuss the state of the art inherent in pedagogical-didactic research on the education of gifted students. To this end, a systematic review of scientific texts published between 2011 and 2021 was carried out. The present article is organized as follows: introduction to the topic; definition of the objectives, research questions, and methodological protocol; selection, evaluation, and synthesis of the abstract studies; discussion and evaluation of the results; and conclusions. Multiple tools for identifying the gifted students (for use by psychologists, pedagogists, educators, and teachers) emerge from the findings of the present study. The texts highlight numerous instructional and educational programming models for gifted students in all school grades. The main model is the SEM—(Schoolwide Enrichment Model). The present review shows a conspicuous production on gifted education, with the predominance of recently published articles (indicative of vivid interest in the topic) and of American origin. This geographic predominance, which does not cover the European and eastern parts of the world, may depend on the fact that the databases used [Scopus and Web of Science (WoS)] select results based on the use of English. This review reveals gaps and emerging trends in gifted education research, suggesting possibilities and future perspectives

Giftedness and peer group: an exploration of the representational repertory on giftedness in the early school age

There has been growing interest in the issue of giftedness and in educational paths which can counteract the development of misrepresentations and negative attitudes on the theme. These forms of common sense contribute to interpreting social reality using shortcuts in thinking that are sometimes inadequate to explain the complexity of human personality and that, therefore, may generate some stereotypes and prejudices. The analysis and orientation of distorted representations could prompt the activation of inclusive behaviour towards gifted peers. This contribution therefore focuses on the representations concerning giftedness in the peer group. The project, carried out with pupils of primary school class, aims to explore the representations and attitudes of children exposed to a path of awareness on giftedness in order to support a correct and inclusive representation of the phenomenon

Demographic Trends and Pensions in Italy: An Outlook for the Future

Projections of expenditures for old age pensions, survivor pensions, and disability pensions were made for the period 1985-2050 on the basis of future developments in the population structure by age, sex, and marital status. Four demographic scenarios were formulated: (i) a Benchmark scenario, with demographic rates kept constant at their 1980-84 level; (ii) a Fertility scenario, with a rise of the Total Fertility Rate (TFR) towards replacement level; (iii) a Mortality scenario, with reductions in mortality rates of 30 percent for females, and 45 percent for males; (iv) a Western scenario, which combines extreme demographic conditions of several West European countries: a TFR of 1.28, proportions never-marrying of one-third, one-third of marriages ending in divorce, and male and female life expectancies of 74 and 81 years, respectively. The current pension system was combined with all four scenarios. Also, the impact of high female labor force participation, and a rise in the average age at retirement were investigated. The results indicate that changes in demographic conditions cannot prevent increases in and funding problems for pension expenditures in Italy. An increase in fertility has no effect on the pension system until 2030, when a larger generation will enter the labor force. Longer active periods for males and females will cause increases in pension expenditures in the future and are not long term solutions of the pension problem. Postponement of retirement age would help to balance the pension funds, but depends on the economic situation and on the labor market

Linguaggio, metacognizione e deficit La funzione adattiva ed evolutiva nel processo di sviluppo e di apprendimento

Saggio introduttivo al numero monografico curato da S. Pinnelli, di ISS- Erickso

PERCEPTION, EXPECTTION AND PREFERENCES TOWARD ICT SOLUTYON OF THE FRAIL ELDERLY PERSON

none1openstefania pinnelliPinnelli, Stefani

Resilience and the pedagogical task: from research-training to transformative educator intervention Resilienza e compito pedagogico: dalla ricerca-formazione all’intervento trasformativo del pedagogista

The concept of resilience describes the ability to resist and cope with the destructive challenges that life sometimes imposes, a process that involves dynamic aspects that support, encourage and promote the ability to struggle, overcome obstacles, alongside biological determinants, caregivers assume a strategic role and constitute the protective factors. The paper exposes the research-training pathway, developed in the 2020-2021 academic year with a class of pedagogists from the University of Salento, a pathway that produced a transformation in the perception of one's role with respect to the educational task, becoming builders of resilience. The active research path enabled the trainees to recognize themselves as resilience builders, identifying projects, areas and specific actions for intervention. The 46 projects implemented were positioned on 4 macro-categories of fragile users and invested the most extensive areas of life, strategies, technologies and intervention models typical of educational action