69 research outputs found

    “One, none, and a hundred thousand” recipes for a robust response to turbulence

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    Turbulence appears to be a “new normal” in current societies, and public organizations need to learn how to react and adapt to it. Scholars agree on the need for robust actions to respond to turbulence. Through a qualitative comparative analysis performed on the vaccination campaigns of all 20 Italian regions, our paper explores whether different and alternative models of robustness may exist to cope with turbulence. Results shed light on three alternative models featuring static, hybrid, and dynamic robustness. They also highlight that robust governance appears to involve a capacity to learn, and to employ this learning as circumstances demand

    HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter

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    Background: Intracellular defense proteins, also referred to as restriction factors, are capable of interfering with different steps of the viral life cycle. Among these, we have shown that Tripartite motif 22 (TRIM22) suppresses basal as well as phorbol ester-induced HIV-1 long terminal repeat (LTR)-mediated transcription, independently of its E3 ubiquitin ligase activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) binding to the U3 region and Tat interaction with the TAR region of the HIV-1 LTR. As basal HIV-1 transcription is driven by the transcription factor specificity protein 1 (Sp1), we have investigated whether TRIM22 could interfere with Sp1-driven transcriptional activation of the HIV-1 LTR. Findings: 293T cells, devoid of endogenous TRIM22 expression, were transfected with a TRIM22-expressing plasmid together with reporter plasmids driven by the HIV-1 LTR promoter either containing or lacking Sp1 binding sites or with reporter plasmids driven by non-viral promoter sequences either containing or lacking the three Sp1 binding sites from the HIV-1 LTR. These reporter assays showed that TRIM22 efficiently inhibited Sp1-driven transcription. Knocking down TRIM22 expression in the CD4+ SupT1 T cell line increased the replication of Sp1-dependent HIV-1 variants. TRIM22 did not interact with Sp1, but prevented binding of Sp1 to the HIV-1 promoter, as demonstrated in protein-DNA pull down and chromatin immunoprecipitation assays. Conclusion: TRIM22 acts as a suppressor of basal HIV-1 LTR-driven transcription by preventing Sp1 binding to the HIV-1 promoter

    Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

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    OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

    Measuring audience addiction to the arts: the case of an Italian theatre

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    Given the importance of addressing national and local public policies towards the creation of a sort of “habituation” or “addiction” to fine arts consumption, relatively few studies have encountered this phenomenon and, above all, few empirical research have been done in order to replicate repeated audience participation in the arts. This paper employs Markov’s theory to describe the audience of an Italian theatre in their path towards “habituation” to fine arts consumption. It also proposes a methodology that can be useful for policy analysts and administrators in evaluating arts institutions’ strategies and policies with respect to existing audiences

    Reti culturali e creazione di capitale sociale

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    Obiettivo del capitolo è investigare la relazione fra creazione di reti culturali e distretti e formazione di capitale sociale interno ed esterno. Ampio spazio è dato al ruolo del management nel costruire e alimentare tale capitale social

    The Managerial Work of Italian City Managers: an Empirical Study

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    Among the measures taken to reform local government in Italy, one of the most significant is the introduction of the post of city manager. In this paper we outline the personal and professional traits of city managers in today’s Italy. The study provides a snapshot of a situation marked by increasing dynamism, but still with a certain degree of conservatism. A picture emerges of a manager with multiple roles, spending most time within the organisation and whose work seems typically orientated towards internal stakeholders rather than external constituencies. However, the changing role of municipalities in the Italian context poses new challenges and these will probably influence the evolution of the content of the managers’ work

    Leader si nasce o si diventa?

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    Il capitolo illustra una rassegna dei principali approcci alla leadership nelle scienze sociali con particolare riferimento alla psicologia sociale e alla scienzaa della politic
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