A "cell-free" system to study regulation of focal adhesions and of the connected actin cytoskeleton.

The exact composition of focal adhesions and the role of single components in their assembly and regulation during dynamic adhesive processes are poorly understood. I have characterised and used a "cell-free" system consisting of ventral plasma membranes (VPMs) prepared from adherent fibroblasts, and found that this subcellular fraction preserves intact focal adhesion components and the connected actin cytoskeleton. Moreover, VPMs show an accumulation of several tyrosine phosphorylated proteins, including tyrosine phosphorylated focal adhesion kinase and paxillin. In particular, a pool of higly phosphorylated paxillin is found in focal adhesions, suggesting an important role for the phosphorylated polypeptide in the mechanism of integrin-mediated adhesion. With the aim of obtaining new important tools for my studies, I have produced and characterised monoclonal antibodies (mAbs) raised against VPM preparations. The use of VPM preparations as a "cell-free" system has shown that changes in [Ca2+] can affect integrin behaviour within VPMs. I observed a correlation between integrin localisation and the functional state of the receptors, which can be reversibly modulated either by changes in free [Ca2+], or by function modulating anti-integrin pi mAbs. [Ca2+]-induced integrin redistribution is dependent on the presence of the pi cytoplasmic domain, whereas it is independent from the presence of filamentous actin (F- actin) and focal adhesion components in this experimental system, thus implicating the uncoupling of events relevants for focal adhesion assembly under "cell-free" conditions. Moreover, reconstitution experiments show that a-actinin colocalises and redistributes with pi receptors on VPMs depleted of actin, implicating binding of a-actinin to the receptors. Finally, I found that recruitment of exogenous actin is specifically restricted to focal adhesions under conditions in which new actin polymerisation is inhibited. These data attest the value of the system for further analysis of the molecular mechanisms regulating integrin function and focal adhesions

Academic failure: individual, organizational, and social factors

The high percentage of university dropouts in Europe underlines the relevance of understanding which factors lead students to leave university and to be dissatisfied with this experience. Previous studies have focused on only some predictors of academic failure. The present study tested a structural equation model with latent variables to determine the impact of psychological, organizational, and relational variables on the intention to drop out of university and dissatisfaction with the university experience. An online survey was completed by 431 university students (M = 23.06, SD = 5.5, 362 females) recruited from different courses at several Italian universities. Results showed that the intention to drop out of university was negatively related to self-efficacy, institutional commitment, and academic integration, and positively related to an external locus of control. Dissatisfaction with the university experience was negatively associated with self-efficacy, institutional commitment, and academic integration. Implications for preventive programs and interventions are presented

Tribal Gaming and Indigenous Sovereignty, With Notes from Seminole Country

"Indigeneity at the Crossroads of American Studies." Published as a special joint issue with American Studies, Volume 46, No. 3/4, Fall 2005

Clinical Impact of two Different Diagnostic Strategies in the First- and Second-Line Treatment of Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

BACKGROUND: A histopathological and mutational diagnosis has become a priority in the correct choice of the most appropriate cancer therapy for NSCLC. In the absence of a molecular analysis, the therapeutic choice will be directed towards platinum-based chemotherapy, thus preventing, in the presence of a specific mutation, the benefits deriving from the administration of a target therapies (TT).AIM: the present analysis was carried out with the aim of estimating the clinical impact, expressed in terms of progression free survival (PFS), associated with the use of the combined strategy (tissue biopsy and liquid biopsy) or the tissue strategy in the EGFR+ mNSCLC population.METHODS: A pre-existing cost-consequence model was adapted to estimate the annual number of mNSCLC patients with or without the EGFR mutation in order to decide the oncological treatment to be administered in first (1L) or second line (2L). In 1L, against the presence of the EGFR mutation, the administration of a Tyrosine Kinase Inhibitor (TKI), such as osimertinib, gefitinib, erlotinib or afatinib, was considered; in the absence of the EGFR mutation, the administration ofstandard platinum-based chemotherapy was instead considered. With reference to 2L, in the presence of the EGFR T790M mutation, only osimertinib was considered. In the absence of the EGFR T790M mutation, the administration of the standard platinum-based chemotherapy was also considered. The PFS data associated with each of the drugs considered were extrapolated from the respective clinical studies. Key variables were tested in the sensitivity analysis.RESULTS: The adoption of the combined strategy (tissue biopsy and liquid biopsy), by virtue of a greater number of patients treated with TKIs, would make it possible to increase the average PFS in the range of 1.1-3,7 months in the 1L and by 1.4 months in the 2L.CONCLUSION: These results show how the adoption of a correct diagnostic strategy is critical in order to optimize the choice of the therapeutic path in the 1L and 2L of mNSCLC. The addition of the liquid biopsy to the classic diagnostic path (tissue biopsy) would in fact allow to obtain an increase in therapeutic efficacy (average PFS)

Adjustment to COVID-19 Lockdown Among Italian University Students: The Role of Concerns, Change in Peer and Family Relationships and in Learning Skills, Emotional, and Academic Self-Efficacy on Depressive Symptoms

In Italy strict containment measures against COVID-19 pandemic were implemented from March to May 2020 with home confinement and schools and universities closed. Students shifted to remote learning, experienced a forced isolation from peers and an increased sharing of time and spaces with the family. The influence of these aspects on the psychological adjustment of university students is largely unexplored. This paper was aimed at investigating the role of some correlates of depressive symptoms specific to the lockdown condition experienced by young university students, namely contagion concern, perceived worsening of family, and peer relationships and perceived worsening of learning skills. Moreover, the possible mediating effects of emotional and academic self-efficacy in these relationships were examined. Data were collected from 296 Italian university students (aged 18–25 years; 83% female students) through an online survey by means of a snowball sampling methodology in May 2020. Significant depressive symptoms were reported by 67% of participants. Contagion concerns were related to depressive symptoms through the mediating effect of emotional self-efficacy. Worsening of learning skills was related to depressive symptoms through the mediating effect of academic self-efficacy. Depressive symptoms were directly related to worsening of family relationships but unrelated to worsening of peer relationships. Results are discussed in relation to the need of preventive interventions for this specific population in view of academic activities planning in the post-COVID 19 period

Parents and children during the COVID-19 lockdown: the influence of parenting distress and parenting self-efficacy on children’s emotional well-being

On March 10, 2020, Italy went into lockdown due to the Coronavirus Disease-19 (COVID-19) pandemic. The World Health Organization highlighted how the lockdown had negative consequences on psychological well-being, especially for children. The present study aimed to investigate parental correlates of children’s emotion regulation during the COVID-19 lockdown. Within the Social Cognitive Theory framework, a path model in which parenting self-efficacy and parental regulatory emotional self-efficacy mediated the relationship between parents’ psychological distress and both children’s emotional regulation, and children’s lability/negativity, was investigated. A total of 277 parents of children aged from 6 to 13 years completed an online survey that assessed their psychological distress, regulatory emotional self-efficacy, and parenting self-efficacy. Parents reported also children’s emotional regulation and lability/negativity. A structural equation model (SEM) using MPLUS 8.3 was tested. Results showed that the hypothesized model exhibited excellent fit, chi-square (83) = 140.40, p < 0.01, RMSEA = 0.05, CFI = 0.97, TLI = 0.96, SRMR = 0.04. The influences of parents’ psychological distress and parents’ regulatory emotional self-efficacy on children’s emotional regulation and lability/negativity were mediated by parenting self-efficacy. The mediation model was invariant across children’s biological sex and age, and geographical residence area (high risk vs. low risk for COVID-19). Results suggested how parents’ beliefs to be competent in managing parental tasks might be a protective factor for their children’s emotional well-being. Implications for intervention programs are discussed