Digitale d'autore. Macchine, archivi, letterature

Il volume parte da una ricognizione introduttiva sul rapporto tra scrittori e computer; dà una definizione degli archivi letterari nati digitalmente, fornisce alcuni esempi nel panorama internazionale e delinea una prima mappatura delle esperienze italiane, soffermandosi in particolare sul caso dell’archivio di Franco Fortini conservato all’Università degli Studi di Siena. Offre una sintesi del primo progetto italiano dedicato al born-digital letterario, PAD – Pavia Archivi Digitali, analizzando i processi di acquisizione e gestione dei fondi, oggi conservati presso il Centro Manoscritti di Pavia. Propone infine un’analisi critica delle prime tre opere di Francesco Pecoraro alla luce dell’archivio digitale conservato a Pavia

ELA: fasi del progetto, bilanci e prospettive

Il contributo ripercorre le fasi di un progetto di start-up (marzo 2018-febbraio 2020) nato per la realizzazione di ELA-Eurasian Latin Archive, una piattaforma digitale di testi latini e multilingua dei secoli XII-XVIII riguardanti l’Estremo Oriente. Il bilancio qui proposto comprende una valutazione generale del lavoro a partire dall’avvio e dalla pianificazione del progetto fino alle “lezioni apprese”, con alcune riflessioni sugli sviluppi attesi in termini di sostenibilità e implementazioni future

Hold it All Together: a Case Study in Quality Control for Born-Digital Archiving

Policies, standards, procedures and software implemented at PAD-Pavia Archivi Digitali (Università di Pavia, Italy) to ensure correct ingest and sustainable long term preservation of digital-native literary papers of Italian writers

Heparan sulfate expression in the neural crest is essential for mouse cardiogenesis

Impaired heparan sulfate (HS) synthesis in vertebrate development causes complex malformations due to the functional disruption of multiple HS-binding growth factors and morphogens. Here, we report developmental heart defects in mice bearing a targeted disruption of the HS-generating enzyme GlcNAc N-deacetylase/GlcN N-sulfotransferase 1 (NDST1), including ventricular septal defects (VSD), persistent truncus arteriosus (PTA), double outlet right ventricle (DORV), and retroesophageal right subclavian artery (RERSC). These defects closely resemble cardiac anomalies observed in mice made deficient in the cardiogenic regulator fibroblast growth factor 8 (FGF8). Consistent with this, we show that HS-dependent FGF8/FGF-receptor2C assembly and FGF8-dependent ERK-phosphorylation are strongly reduced in NDST1(-/-) embryonic cells and tissues. Moreover, WNT1-Cre/LoxP-mediated conditional targeting of NDST function in neural crest cells (NCCs) revealed that their impaired HS-dependent development contributes strongly to the observed cardiac defects. These findings raise the possibility that defects in HS biosynthesis may contribute to congenital heart defects in humans that represent the most common type of birth defect

Gi/o-protein coupled receptors in the aging brain

Cells translate extracellular signals to regulate processes such as differentiation, metabolism and proliferation, via transmembranar receptors. G protein-coupled receptors (GPCRs) belong to the largest family of transmembrane receptors, with over 800 members in the human species. Given the variety of key physiological functions regulated by GPCRs, these are main targets of existing drugs. During normal aging, alterations in the expression and activity of GPCRs have been observed. The central nervous system (CNS) is particularly affected by these alterations, which results in decreased brain functions, impaired neuroregeneration, and increased vulnerability to neuropathologies, such as Alzheimer's and Parkinson diseases. GPCRs signal via heterotrimeric G proteins, such as Go, the most abundant heterotrimeric G protein in CNS. We here review age-induced effects of GPCR signaling via the Gi/o subfamily at the CNS. During the aging process, a reduction in protein density is observed for almost half of the Gi/o-coupled GPCRs, particularly in age-vulnerable regions such as the frontal cortex, hippocampus, substantia nigra and striatum. Gi/o levels also tend to decrease with aging, particularly in regions such as the frontal cortex. Alterations in the expression and activity of GPCRs and coupled G proteins result from altered proteostasis, peroxidation of membranar lipids and age-associated neuronal degeneration and death, and have impact on aging hallmarks and age-related neuropathologies. Further, due to oligomerization of GPCRs at the membrane and their cooperative signaling, down-regulation of a specific Gi/o-coupled GPCR may affect signaling and drug targeting of other types/subtypes of GPCRs with which it dimerizes. Gi/o-coupled GPCRs receptorsomes are thus the focus of more effective therapeutic drugs aiming to prevent or revert the decline in brain functions and increased risk of neuropathologies at advanced ages.This work was supported by Fundação para a Ciência e Tecnologia, Centro 2020 and Portugal 2020, the COMPETE program, QREN, and the European Union (FEDER program) via the GoBack project (PTDC/CVT-CVT/32261/2017), the pAGE program (Centro-01-0145-FEDER-000003), and Institute for Biomedicine iBiMED (UID/BIM/04501/2013; UID/BIM/04501/2019).publishe