661 research outputs found

    Strategies for the selective targeting of specific G-quadruplex structures

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    Mounting evidence suggests that nucleic acids able to fold into G-quadruplex structures play pivotal roles in the regulation of various and relevant biological processes. However, ligands that are selective for specific G4 structures are currently lacking. This is due to the high structural similarity of G4s, making specific targeting extremely challenging. Despite this, there is an urgent need of such tools as a mean to better understand G4 biological activity and to investigate their potential as therapeutic targets. In order to bridge this gap, three strategies are proposed in this work, that is the structural optimization of pre-existing ligands, the reduction of non-specific interactions, the recognition of sequences proximal to the G4 of interest, in a crescendo of specificity.Un numero crescente di evidenze indica che gli acidi nucleici capaci di ripiegarsi a G-quadruplex regolano vari e rilevanti processi biologici. Tuttavia, non sono ad ora disponibili leganti selettivi per specifici G4, data la loro elevata somiglianza strutturale. Nonostante ciò, tali strumenti sono necessari per poter meglio comprendere il ruolo biologico dei G-quadruplex e ai fini di valutarne le potenzialità come bersagli terapeutici. Per colmare tale lacuna, in questa tesi proponiamo tre strategie, l’ottimizzazione strutturale dei leganti, la riduzione delle interazioni aspecifiche, il riconoscimento di sequenze vicine al G4 stesso, in un crescendo di specificità

    Apolipoprotein E in Alzheimer’s Disease

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    The pathophysiology of Alzheimer’s disease (AD) is related with the ongoing deterioration of brain lipid homeostasis, in which the cholesterol transporter apolipoprotein E (APOE) plays a key role. Plasma protein APOE might be additionally associated with AD due to its capability to bind the amyloid protein. There are three principal isoforms: APOE2, APOE3 and APOE4, encoded by three different alleles (ε2, ε3, ε4). Among them, APOE4 is recognized as the toxic form involved in AD development and progression. In fact, the presence of the ε4 allele correlates to an increase of about three times in the risk of developing the disease in late onset forms, both familiar and sporadic. For this reason, APOE4 has been often highlighted as a promising therapeutic target. Nevertheless, recent studies also suggest that the reduction of APOE protein levels, regardless of the isoform present, might be beneficial to deal with AD progression. Herein we report a brief overview of the proposed roles of APOE and in particular of ApoE4 in the insurgence and development of AD. In particular, its intervention in amyloid-β dependent and independent processes are examined. New therapeutic approaches for AD exploiting APOE as a target are finally discussed

    Celebrity Endorsement and congruence: an Experimental Study

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    Celebrity endorsement is a more and more used tool within the domain of psychology of marketing and advertising. Beside the fact of showing famous and, generally, beautiful people, it is not at all clear if such a marketing device works and, if so, under which conditions. The present study aims at verifying at which level the power of influence of celebrity endorsement works. In particular, we hypothesize that celebrity endorsement effect is stronger when the star promotes something which can be seen by the audience as belonging to the world of the star him/herself, what is known in literature as congruence. In other words, we hypothesize that a sport star, for example, will be more effective when promoting some product related to the sport world, like, for example, sport equipment, rather than when promoting something which does not make direct reference to her/his world, like food, in this case. In the preliminary study we have tested the supposed over-use of celebrity endorsement by an analysis of 1801 tv ads and, in addition, we have recorded which type of products celebrities are used to promote. In the core study we have tested the effectiveness of celebrity endorsement in relation to the congruence between endorser and product. According to our manipulation checks, we have prepared 4 different printed advertisements; 2 of them involving, as celebrity, ex-Miss Italy, Martina Colombari, who now is a popular Italian actress and 2 of them involving a common person. For each of the above mentioned conditions (celebrity vs non-celebrity) we have prepared 2 different advertisements, one promotes a perfume and the other one a tomato-sauce, which is the way by which we have operazionalized the variable “congruence”. The paper presents the main results according to which celebrity endorsement is very effective, without significant differences in terms of product type

    Photoresponsive molecular devices targeting nucleic acid secondary structures

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    Non B-DNA structures are non-canonical nucleic acid conformations adopted by single strands fulfilling specific sequence requirements. Numerous experimental evidences support their roles as regulators of biological processes, involving genetic information transfer. However, direct visualization of the folding and unfolding of such structures in live cells still remains elusive, as well as a detailed understanding of their mechanisms of action and functions. Fluorescent light-up probes are excellent tools to address these pending questions. This review aims at classifying the multitude of dyes available to date in terms of operating mechanism (conformational restriction, TICT, aggregation related phenomena, conjugation, etc.) and targeted structures. The most promising results are presented for each conformational class, contextually highlighting the main criticalities and the remaining gaps

    Students' academic performance and employability: A study on Italian undergraduates

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    Nowadays, a very high level of unemployment constitutes the normal structure of individuals’ work life in Italy. Organizational changes (i.e. m&a, layoffs or downsizing) lead individuals to job insecurity (Sverke & Hellgren, 2002) and thus to a natural decline in job performance and self-perceived employability. This paper analysed the differences in academic performance in comparison to ambition, self-perceived employability and university commitment (Rothwell et al. 2008) and the psychometric properties of the above mentioned scales. We assumed that students will be more motivated to perform well in education if they believe that their efforts will lead to the “right job” – rather than the “secure one” (Ortiz, 2008). An initial Italian validation of Rothwell’s et al. (2008) scales has been done and differences in ambition, self-perceived employability and high performance among students was verified in a sample of 115 senior-year students. Results and practical implications are then described

    Student Cynicism: An Initial Italian Validation of C.A.T.C.S. (Cynical Attitudes Toward College Scale)

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    AbstractStudent cynicism is an attitude characterized by a sense of frustration and negative beliefs mainly due to disillusion of expectations about students’ own course of studies. It could be directed towards academic experience in general, or towards specific aspects of the academic environment. It consists of emotional, cognitive and behavioral dimensions and could be used as an indicator of distress, insecurity and disinvestment towards the academic environment. Brockway et al. (2002) produced an 18- item self-report questionnaire to measure student cynicism, named Cynical Attitudes Toward College Scale (CATCS)

    Red/NIR G-Quadruplex Sensing, Harvesting Blue Light by a Coumarin-Naphthalene Diimide Dyad

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    A conceptually new light-up nucleic acid fluorescent probe resulting from the conjugation of a coumarin to a naphthalene diimide exhibits a single wavelength emission at 498 nm when free in solution and an additional red/NIR emission when bound to G-quadruplex DNA. The light-up response centred at 666 nm is highly specific for quadruplex DNA when compared to duplex DNA or to RNA quadruplexes
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