Catasto, fiscalità e lotta politica nella Toscana nel XVIII secolo

L’articolo prende in esame i tentativi compiuti nella seconda metà del XvIII secolo dai Lorena – e segnatamente dal granduca riformatore, Pietro Leopoldo- di realizzare nel granducato di Toscana un moderno ed uniforme catasto parti- cellare: quel Granducato che costituisce, com’è noto, uno dei più interessanti e vivaci laboratori o politici di tutto il Settecento europeo. È parso utile tornare su un tema che è stato considerato da svariati autori semplicemente come un caso di ‘riforma fallita’, per cercare di mettere in luce, a seguito anche di nuovi scavi documentari, il ricco quadro delle discussioni e degli schieramenti politici che accompagnarono questo reale o supposto fallimento. Sostanzialmente assente dal dibattito politico negli anni della reggenza lorenese di Francesco Stefano (1737-1765), la questione del catasto emerge all’attenzione nel 1763, ma è con la successione al trono granducale di Pietro Leopoldo che essa diviene il centro di un animato e conflittuale dibattito politico. Sostenuta dalla volontà di riforma del granduca e da un gruppo di suoi collaboratori di orientamento filo-fisiocratico, l’opportunità di procedere ad un complessivo ed uniforme rinnovamento dei catasti pare affermarsi, ed ha inizio dopo molte vivaci discussioni un’intensa sperimentazione in varie parti dello stato. Tuttavia, nonostante i parziali successi ottenuti, l’idea di un nuovo generale catasto viene per molteplici motivi - tra cui primario l’opposizione della classe dei grandi proprietari terrieri fiorentini - abbandonata nel 1785. Ma la vicenda del piccolo laboratorio toscano riflette fedelmente anche il cambiamento di clima del tardo illuminismo europeo. Le difficoltà dell’ assolutismo illuminato, il superamento delle dottrine fisiocratiche ed il diffondersi delle nuove dottrine economiche inglesi concorrono a determinare l’abbandono del progetto di nuovo catasto, che agli occhi dei contempora- nei rappresentava il modello di una società fortemente diretta dallo stato

High-throughput analysis of the RNA-induced silencing complex in myotonic dystrophy type 1 patients identifies the dysregulation of miR-29c and its target ASB2

Myotonic dystrophy type 1 (DM1) is a multi-systemic disorder caused by abnormally expanded stretches of CTG DNA triplets in the DMPK gene, leading to mutated-transcript RNA-toxicity. MicroRNAs (miRNAs) are short non-coding RNAs that, after maturation, are loaded onto the RISC effector complex that destabilizes target mRNAs and represses their translation. In DM1 muscle biopsies not only the expression, but also the intracellular localization of specific miRNAs is disrupted, leading to the dysregulation of the relevant mRNA targets. To investigate the functional alterations of the miRNA/target interactions in DM1, we analyzed by RNA-sequencing the RISC-associated RNAs in skeletal muscle biopsies derived from DM1 patients and matched controls. The mRNAs found deregulated in DM1 biopsies were involved in pathways and functions relevant for the disease, such as energetic metabolism, calcium signaling, muscle contraction and p53-dependent apoptosis. Bioinformatic analysis of the miRNA/mRNA interactions based on the RISC enrichment profiles, identified 24 miRNA/mRNA correlations. Following validation in 21 independent samples, we focused on the couple miR-29c/ASB2 because of the role of miR-29c in fibrosis (a feature of late-stage DM1 patients) and of ASB2 in the regulation of muscle mass. Luciferase reporter assay confirmed the direct interaction between miR-29c and ASB2. Moreover, decreased miR-29c and increased ASB2 levels were verified also in immortalized myogenic cells and primary fibroblasts, derived from biopsies of DM1 patients and controls. CRISPR/Cas9-mediated deletion of CTG expansions rescued normal miR-29c and ASB2 levels, indicating a direct link between the mutant repeats and the miRNA/target expression. In conclusion, functionally relevant miRNA/mRNA interactions were identified in skeletal muscles of DM1 patients, highlighting the dysfunction of miR-29c and ASB2

Nature as a preferential habitat in growth and socialisation processes in autism. A structured intervention

Dysfunctionality in socialisation is undoubtedly the most crucial characteristic of autism. For a long time, social functioning and its improvement have been considered among the most important interventions in the literature. Individuals with autism are responsive to therapist-mediated and/or peer-mediated interventions that increase their social engagement. The present study examines the impact of outdoor integrated activities, such as music therapy, equine-assisted therapy, and art therapy, in autistic individuals (n=14). The analysis was carried out on the application of a questionnaire assessing three social skill domains: Joint Attention (JA), Imitation (IMI), and Turn-Taking (T-T) mediated by the therapists and by peers. The development and acquisition of these social behaviours were examined in a structured outdoor context (ASO). Data were collected by two independent observers by White's Scale questionnaire. The results revealed that the proposed interventions facilitated and led to an increase in social-behavioural experience

Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives

Targeting protein-protein interactions (PPIs) has been recently recognized as an emerging therapeutic approach for several diseases. Up today, more than half a million PPI dysregulations have been found to be involved in pathological events. The dynamic nature of these processes and the involvement of large protein surfaces discouraged anyway the scientific community in considering them promising therapeutic targets. More recently peptide drugs received renewed attention since drug discovery has offered a broad range of structural diverse sequences, moving from traditionally endogenous peptides to sequences possessing improved pharmaceutical profiles. About 70 peptides are currently on the marked but several others are in clinical development. In this review we want to report the update on these novel APIs, focusing our attention on the molecules in clinical development, representing the direct consequence of the drug discovery process of the last 10 years. The comprehensive collection will be classified in function of the structural characteristics (native, analogous, heterologous) and on the basis of the therapeutic targets. The mechanism of interference on PPI will also be reported to offer useful information for novel peptide desig