Characterization of the Caspr2 and NLGN2 ligands: a proteomic and biochemical approach

Autism Spectrum Disorder (ASD) is a range of early-onset conditions classified as neurodevelopmental disorders, characterized by deficits in social interactions and communication, as well as by restricted interest and repetitive behaviors. Among the proteins associated with this spectrum of disease there are Caspr2, α-NRXN1, NLGN1-4. Caspr2 is involved in the clustering of K+ channels at the juxtaparanodes, where it is proposed to bind TAG-1. Recent works reported a synaptic localization of Caspr2, but little is know on its role in this compartment. NRXNs and their ligand NLGNs, instead, have a well-defined role in the formation and maintenance of synapses. Among the neuroligins, NLGN2 binds NRXNs with the lowest affinity, suggesting that it could have other not yet characterized ligands. The aim of this work was to better characterize the binding of Caspr2 to TAG-1 and to identify new potential binding partner for Caspr2 and NLGN2. Unexpectedly, using Isothermal Titration Calorimetry and co-immunoprecipitation experiments the direct association of the first two proteins could not be verified and the results indicate that the first evidences reporting it were biased by false-positive artifacts. These findings, together with the uncharacterized synaptic localization of Caspr2, made the identification of new potential binding partners for this protein necessary. To find new proteins that associate with Caspr2 and NLGN2, affinity chromatography in tandem with mass spectrometry experiments were performed. Interestingly, about 25 new potential partners were found for these two proteins and NLGN1, that was originally included as a control: 5 of those, namely SFRP1, CLU, APOE, CNTN1 and TNR, were selected for further investigations. Only the association of CLU to NLGN2 was confirmed. In the future, screenings of the remaining candidates have to be carried out and the functional role for the proposed NLGN2-CLU complex has to be studied.

Envy: A Psychometric Refinement of the Construct

The noticeable differences in the theoretical and operative definitions of envy across studies and approaches have produced a fragmentary representation and understanding of the envious emotion. The present dissertation aimed to clarify the inherent nature of the construct of envy through the integration of findings from three independent studies. We focused on malicious envy, and investigated it from both a dispositional and an episodic perspective. Studies 1 and 2 investigated the dimensionality of envy as a stable individual characteristic and an episodic emotional state, respectively. In order to elicit episodic envy, a scenario-based experiment was conducted. Results indicated that, in both its dispositional and episodic facets, envy is a bidimensional construct composed by an inner-directed dimension of inferiority and helplessness, and an outer-directed dimension of feelings of anger and ill will. Moreover, findings from Study 1 allowed to establish boundaries between envy and competing constructs that have often been included in conceptualizations of envy. The psychometrically validated definition of envy provided by Studies 1 and 2 represents a valuable contribution to empirical research. Implications for envy research concern the promotion of a shared operationalization of envy in future studies, which will arguably facilitate the comparison of findings between studies and between approaches. Study 3 examined the mechanisms through which dispositional envy affects individuals’ social adjustment and psychological wellbeing. Findings revealed that the detrimental effects of envy on perceived social support and subjective well-being are mostly mediated by other personal characteristics, such as neuroticism and self-esteem. By reducing global self-esteem, the envious disposition may damage supportive social networks via antisocial direct and indirect behaviors that may arise from envy and that are likely to drive others away. On the other hand, by damaging both emotional stability and self-worth, dispositional envy leads to reduced subjective well-being. Implications for clinical practice are discussed.

Fighting corruption with pyramids: A Law and Economics approach to combating corruption in post-socialist countries

Corruption is, in the last two decades, considered as one of the biggest problems within the international community, which harms not only a particular state or society but the whole world. The discussion on corruption in law and economics approach is mainly run under the veil of Public choice theory and principal-agent model. Based on this approach the strong international initiatives taken by the UN, the OECD and the Council of Europe, provided various measures and tools in order to support and guide countries in their combat against corruption. These anti-corruption policies created a repression -prevention-transparency model for corruption combat. Applying this model, countries around the world adopted anti-corruption strategies as part of their legal rules. Nevertheless, the recent researches on the effects of this move show non impressive results. Critics argue that “one size does not fit all” because the institutional setting of countries around the world varies. Among the countries which experience problems of corruption, even though they follow the dominant anti-corruption trends, are transitional, post-socialist countries. To this group belong the countries which are emerging from centrally planned to an open market economy. The socialist past left traces on institutional setting, mentality of the individuals and their interrelation, particularly in the domain of public administration. If the idiosyncrasy of these countries is taken into account the suggestion in this thesis is that in public administration in post-socialist countries, instead of dominant anti-corruption scheme repression-prevention-transparency, corruption combat should be improved through the implementation of a new one, structure-conduct-performance. The implementation of this model is based on three regulatory pyramids: anti-corruption, disciplinary anti-corruption and criminal anti-corruption pyramid. This approach asks public administration itself to engage in corruption combat, leaving criminal justice system as the ultimate weapon, used only for the very harmful misdeeds.

Tecniche investigative ed aspetti criminologici nelle indagini giudiziarie relative ai suicidi ed alle morti equivoche. L'autopsia psicologica

La ricerca è strutturata in due sezioni: nella prima, dopo una premessa storica sul suicidio ed una lettura dei relativi dati statistici italiani integrata dall’analisi delle principali teorie sociologiche e dei principali aspetti psicopatologici e di psicologia clinica, vengono esaminati i risultati forniti da numerosi studi scientifici sul tema complementare delle morti equivoche, con particolare riferimento alle categorie a rischio rappresentate da anziani, carcerati, piloti di aerei, soggetti dediti a pratiche di asfissia autoerotica o roulette russa, istigatori delle forze di polizia e suicida stradali. Successivamente sono esaminati gli aspetti investigativi e medico-legali in tema di suicidi e morti equivoche con particolare riferimento alla tecnica dell’autopsia psicologica analizzandone le origini ed evoluzioni, il suo ambito di utilizzo ed i relativi aspetti metodologici. Nella seconda sezione del lavoro il tema dei suicidi e delle morti equivoche viene approfondito grazie all’apporto di professionisti di discipline diverse esperti in materia di autopsia psicologica ed indagini giudiziarie. A questi è stata presentata, con l’utilizzo della tecnica qualitativa “Dephi, una iniziale ipotesi di protocollo di autopsia psicologica, con le relative modalità applicative, al fine di procedere ad una sua revisione ed adattamento alle esigenze operative italiane grazie alle specifiche esperienze professionali e multidisciplinari maturate dagli esperti. I dati raccolti hanno permesso di giungere alla formulazione di un protocollo di autopsia psicologica, basato sulla elaborazione di domande generali, specifiche e conclusive, a risposta aperta, che possono esser formulate, secondo le modalità previste, alle persone affettivamente significative per la vittima nei confronti della quale si intende procedere con tale strumento investigativo.

The market manipulation regime in the European Union

Market manipulation is an illegal practice that enables a person can profit from practices that artificially raise or lower the prices of an instrument in the financial markets. Its prohibition is based on the 2003 Market Abuse Directive in the EU. The current market manipulation regime was broadly considered as a big success except for enforcement and supervisory inconsistencies in the Member States at the initial. A review of the market manipulation regime began at the end of 2007, which became quickly incorporated into the wider EU crisis-era reform program. A number of weaknesses of current regime have been identified, which include regulatory gaps caused by the development of trading venues and financial products, regulatory gaps concerning cross-border and cross-markets manipulation (particular commodity markets), legal uncertainty as a result of various implementation, and inefficient supervision and enforcement. On 12 June 2014, a new regulatory package of market abuse, Market Abuse Regulation and Directive on criminal sanctions for market abuse, has been adopted. And several changes will be made concerning the EU market manipulation regime. A wider scope of the regime and a new prohibition of attempted market manipulation will ensure the prevention of market manipulation at large. The AMPs will be subject to strict scrutiny of ESMA to reduce divergences in implementation. In order to enhance efficiency of supervision and enforcement, powers of national competent authorities will be strengthened, ESMA is imposed more power to settle disagreement between national regulators, and the administrative and criminal sanctioning regimes are both further harmonized. In addition, the protection of fundamental rights is stressed by the new market manipulation regime, and some measures are provided to guarantee its realization. Further, the success EU market manipulation regime could be of significant reference to China, helping China to refine its immature regime.