La firma dell’artista nel contesto dello happening. Joseph Pascali fecit anno in Requiescat in Pace Corradinus di Pino Pascali alla Mostra a soggetto della galleria La Salita.

Pino Pascali’s Requiescat in Pace Corradinus is a happening that took place on 22nd July 1965 in the castle of Torre Astura, in the frame of an exhibition promoted by La Salita gallery (Rome). The artist performed a funeral rite in a crypt, in front of a ‘fake’ monument – that he made– in memoriam of Conradin of Swabia. Here his own signature is present as an inscription: Joseph Pascali fecit anno. This happening – one of the first example in Italy – constitutes a significant case study that consents us to focus on what happen to the signature during a phase of radical mutation of the artistic media.Pino Pascali’s Requiescat in Pace Corradinus is a happening that took place on 22nd July 1965 in the castle of Torre Astura, in the frame of an exhibition promoted by La Salita gallery (Rome). The artist performed a funeral rite in a crypt, in front of a ‘fake’ monument – that he made– in memoriam of Conradin of Swabia. Here his own signature is present as an inscription: Joseph Pascali fecit anno. This happening – one of the first example in Italy – constitutes a significant case study that consents us to focus on what happen to the signature during a phase of radical mutation of the artistic media

RT-QuIC analysis of peripheral tissues and body fluids collected from patients with primary and secondary tauopathies

Neurodegenerative diseases(NDs)are fatal and incurable conditionscharacterized bythe progressive accumulation in specific brain regions of abnormally folded(misfolded)proteins, which are considered disease-specific biomarkers (DSB).These misfoldedproteins are able to spread through neuroanatomical connected regions and to accelerate the conformational conversion of native monomers (seeding), thus progressively amplifying the pathological process. Primary tauopathies are NDs associated withthe accumulation of misfolded tau and include Corticobasal degeneration (CBD), Progressive supranuclear palsy (PSP), Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and other cases of Frontotemporal dementia (FTD). Alzheimer\u2019s disease (AD) can be considered a secondary tauopathy as it is characterized by tau misfolding in addition to amyloid-\u3b2 (A\u3b2) protein deposition. Synucleinopathies comprise a group of NDsassociated with the accumulation of misfolded \u3b1-synuclein (\u3b1S), including Parkinson\u2019s disease (PD) and other atypical parkinsonisms known as Multiple system atrophy (MSA) and Dementia with Lewy bodies (DLB).Given the overlap between clinical symptoms amongNDsand the lackofsensitive and specificdiagnostic tests, the definite diagnosis of NDs lay on neuropathological detectionof these misfolded proteinsin post-mortembrain tissues. However, recent findings have raised the possibility that trace-amount of DSBmight circulate in peripheral tissues and body fluids of affected individuals, thus constituting easily accessiblebiomarkers. For this reason, in my PhD projectweevaluated the ability of an extremely sensitivetechnique, named Real-Time Quaking Induced Conversion (RT-QuIC), to detect seeding activity of misfolded tau eventually present in peripheral tissues, such as olfactory mucosa (OM), and body fluids(urine and cerebrospinal fluid)collected from patients with clinical diagnosis of primary (FTDP-17, FTD, PSP, CBD) and secondary (AD) tauopathies.RT-QuIC assaywas optimized using a recombinant tau protein fragment named tauK18 (4R-tau)as substrate, whose aggregation was efficiently triggered(seeded) by the addition of minute amount (attograms) of tauK18 pre-formed fibrils (PFFs)previouslygenerated in vitro.We demonstrated that tauK18 RT-QuIC assay wasable to detect seeding activity of misfolded tau contained in brain samples of neuropathologically confirmed cases of FTDP-17, PSP,and AD. Thus, we performed RT-QuIC analysis of (i) OM, (ii) CSF and (iii) exosomes extracted from urine samples collected from patients with different primary and secondary tauopathies. As a comparison,we included in theanalysis samples belonging topatients with different synucleinopathies (PD,MSA,and DLB), Multiple sclerosis (MS), Non-demented patients (NDP) and healthy controls (HC). Results showed that tauK18 RT-QuIC assay was able to detect tau seeding activity in CBD and PSP OM samples, but also in some PD, MSA, DLB and MS cases. Similarly, RT-QuIC analysis of CSF samples displayed smalldifferences in tauseeding activity between AD and NDP cases. On the other hand, RT-QuIC analysis of urinary exosomes revealed that AD, FTD and CBD samples triggered tauK18 aggregation with higher efficiency if compared to HC, thus potentially discriminating between tauopathies and healthy subjects. We investigated the ability of PFFs generated in vitrofrom other NDs-associated proteins (3R-tau fragment named tauK19, \u3b1S, A\u3b21-40,and A\u3b21-42) to influence tauK18 aggregation (cross-seeding) and we found that some conformational variants of \u3b1S PFFs were able to cross-seed tauK18 aggregation, thus representing a potential issue for our assayand possibly explaining results obtained with theanalysis of OM samples. Moreover, preliminary structural analysis showed that final reaction productswere characterized by different morphologies when seeded by different (i) OM samples or by (ii) PFFs generated in vitrofrom tauK19, \u3b1S, A\u3b21-40,and A\u3b21-42, suggesting that biophysical assessments might help in discriminating between different seeding-competent samples. Although further retrospective analysis isrequired to confirm results obtained with ourtauK18 RT-QuIC assay, this preliminary study might lay the basis for the development of a new diagnostic approachwhich combines RT-QuIC and biophysical techniques to detect tau seeding activity in peripheral tissues and body fluids of patients with tauopathiesand to discriminatebetween different pathological conditions

Long Noncoding RNA \u201cEPR\u201d controls epithelial cell proliferation by coordinating CDKN1A transcription and mRNA decay in response to TGF-\u3b2

Long noncoding RNAs (lncRNAs) are emerging as regulators of fundamental biological processes. Here we report on the functional characterization of an intergenic lncRNA (lincRNA) expressed in epithelial tissues which we termed EPR (Epithelial cell Program Regulator). EPR is rapidly downregulated by TGF-\u3b2 and its sustained expression largely reshapes the transcriptome, favors the acquisition of epithelial traits, and reduces cell proliferation in cultured mammary gland cells as well as in an animal model of orthotopic transplantation. EPR generates a small peptide that localizes at epithelial cell junctions but the RNA molecule per se accounts for the vast majority of EPR-induced gene expression changes. Mechanistically, EPR interacts with chromatin and regulates Cdkn1a gene expression by affecting both its transcription and mRNA decay through its association with the transcription factor SMAD3 and the mRNA decay promoting factor KHSRP, respectively. We propose that EPR enables epithelial cells to control proliferation by modulating waves of gene expression in response to stimuli

Universal Design for Learning and Inclusive Teaching: Future Perspectives

This contribution aims to reflect on the didactic and methodological changes brought about by Distance Learning, with particular regard to the concept of Inclusive Teaching. During the last year, in fact, the epidemiological emergency dictated by Covid-19 has led to the emergence of new needs, imposing a redesign of tools and resources in use. All this has had a strong impact on students with disabilities and Specific Learning Disorders (SLD), who, in addition to having fewer digital skills than their European peers, were suddenly forced to follow lessons at home without the physical support of the teacher. It was necessary, in fact, to think and re-think about the design of inclusive educational interventions. From a methodological and conceptual point of view, Inclusive Teaching is linked to the concept of Universal Design for Learning (UDL), an inclusive psycho-pedagogical approach that aims to break down the barriers that exist in learning processes. During the pandemic period, one of the major challenges that scholars have begun to consider is applying the UDL approach, generally used in in-person classes, lectures and online courses

A Compass to Drive Collaborative Design Practices within Private Organisations

Collaboration has currently become a must within design practices. Ranging from public to private sector, from social to business, the design activity is no longer commissioned ‘for’ the client, but is carried out ‘with’ the client and with all the stakeholders involved. This tendency introduces a reflection on the shift in design practice and the role of the designer within the community with which she is designing.This article focuses on collaborative design practices within the private sector, providing a set of case studies analysed through variables that define the main qualities of such activities.Those variables become lenses through which it is possible to zoom in on the peculiarity of the session and ultimately draw an evaluation. The correlations of the variables represent a first draft of a compass aimed at building awareness and providing guidelines for future practices.

Multicellular Tumor Spheroids in Nanomedicine Research: A Perspective

Multicellular tumor spheroids are largely exploited in cancer research since they are more predictive than bi-dimensional cell cultures. Nanomedicine would benefit from the integration of this three-dimensional in vitro model in screening protocols. In this brief work, we discuss some of the issues that cancer nanomedicine will need to consider in the switch from bi-dimensional to three-dimensional multicellular tumor spheroid models

MASSIVE CODESIGN

This book focuses on “massive codesign”: the idea that multiple and/or numerous participants having different voices collaborate in a design pro- cess broken down into different steps and formats and resulting in a relevant and diversified amount of data. Services, strategies and scenarios are presented as the main field of ap- plication: these are complex items that demand complex processes be tac- kled, processes in which it is necessary to involve a variety of players who are largely interdependent and therefore who must collaborate in order to achieve any goal. The book essentially makes two main contributions: a “Collaborative De- sign Framework” to identify and structure codesign activities, methods and tools within massive creative processes; a “set of quick lessons learnt” to provide guidance to the conception and organisation of other massive crea- tive processes. The whole book is oriented at practice: it discusses codesign activities from the designer’s point of view, detailing issues such as process from beginning to end, activity flow, manipulability of tools, roles and rules for participants and many others. It is intended as a support for designers dealing in massive codesign processes and aims towards improved results

Accelerated aging in perinatally HIV-infected children: clinical manifestations and pathogenetic mechanisms

BACKGROUND: Premature aging and related diseases have been documented in HIV-infected adults. Data are now emerging also regarding accelerated aging process in HIV-infected children. METHODS: A narrative review was performed searching studies on PubMed published in English language in 2004-2017, using appropriate key words, including "aging", "children", "HIV", "AIDS", "immunosenescence", "pathogenesis", "clinical conditions". RESULTS: Premature immunosenescence phenotype of B and T cells in HIV-infected children is mediated through immune system activation and chronic inflammation. Ongoing inflammation processes have been documented by increased levels of pathogen-associated molecular patterns (PAMPS), increased mitochondrial damage, higher levels of pro-inflammatory cytokines, and a positive correlation between sCD14 levels and percentages of activated CD8+ cells. Other reported features of premature aging include cellular replicative senescence, linked to an accelerated telomeres shortening. Finally, acceleration of age-associated methylation pattern and other epigenetic modifications have been described in HIV-infected children. All these features may favor the clinical manifestations related to premature aging. Lipid and bone metabolism, cancers, cardiovascular, renal, and neurological systems should be carefully monitored, particularly in children with detectable viremia and/or with CD4/CD8 ratio inversion. CONCLUSION: Aging processes in children with HIV infection impact their quality and length of life. Further studies regarding the mechanisms involved in premature aging are needed to search for potential targets of treatment

IGF-I influences everolimus activity in medullary thyroid carcinoma

Context: Medullary thyroid carcinoma (MTC) is a rare tumor originating from thyroid parafollicular C cells. It has been previously demonstrated that insulin-like growth factor I (IGF-I) protects MTC from the effects of antiproliferative drugs. Everolimus, an mTOR inhibitor, has shown potent antiproliferative effects in a human MTC cell line, TT, and in two human MTC primary cultures. Objective: To verify whether IGF-I may influence the effects of everolimus in a group of human MTC primary cultures. Design: We collected 18 MTCs that were dispersed in primary cultures, treated without or with 10 nM-1 mu M everolimus and/or 50 nM IGF-I. Cell viability was evaluated after 48 h, and calcitonin (CT) secretion was assessed after a 6 h incubation. IGF-I receptor downstream signaling protein expression profile was also investigated. Results: Everolimus significantly reduced cell viability in eight MTC [by similar to 20%; P < 0.01 vs. control; everolimus-responders (E-R) MTCs], while cell viability did not change in 10 MTCs [everolimus-non-responders (E-NR) MTCs]. In E-R MTCs, IGF-I blocked the antiproliferative effects of everolimus that did not affect CT secretion, but blocked the stimulatory effects of IGF-I on this parameter. IGF-I receptor downstream signaling proteins were expressed at higher levels in E-NR MTC as compared to E-R MTCs. Conclusion: IGF-I protects a subset of MTC primary cultures from the antiproliferative effects of everolimus and stimulates CT secretion by an mTOR mediated pathway that, in turn, may represent a therapeutic target in the treatment of aggressive MTCs