"Dentro le mura": le presenze di artisti lucchesi negli inventari cittadini tra Sei e Settecento.

In questo lavoro, che si articola in tra distinte sezioni, mi sono occupato di alcune questioni relative al collezionismo lucchese tra Seicento e, soprattutto, Settecento. Nella prima sezione, ho cercato di ricostruire le testimonianze storiche riguardanti la conoscenza delle quadrerie nobiliari lucchesi, basandomi in primis sulle numerose testimonianze dei viaggiatori e grand-tourists stranieri (Nicolas Audebert, Michel Eyquem de Montaigne, Montesquieu, Georg Christoph Martini ed altri) giunti in Italia dal Cinquecento in poi allo scopo di conoscere e studiare le bellezze dei luoghi e dell’arte, che scelsero Lucca come una delle tappe del loro percorso, sia sulle notizie offerte dalle guide della città pubblicate tra l’Ottocento (Tommaso Trenta, Antonio Mazzarosa, Enrico Ridolfi) e il secolo scorso (Isa Belli Barsali). Ho poi allargato il quadro sviluppando alcune considerazioni relative alle motivazioni ed agli orientamenti di gusto che stanno alla base della formazione di una quadreria, ponendo attenzione alla scelta dei dipinti e alla loro distribuzione nelle pareti. Questi due aspetti possono essere ricostruiti attraverso la consultazione degli inventari, visto che la maggior parte delle collezioni è stata alienata tra Otto e Novecento a seguito dell’abolizione dell’istituzione fedecommissaria e del declino economico delle antiche famiglie nobiliari. Molti degli inventari che ho consultato sono stati redatti dai Pubblici Banditori e Stimatori della Repubblica nell’occasione di divisioni ereditarie, vendite all’incanto e fallimenti. Per questo motivo ho ritenuto opportuno fornire alcune indicazioni sull’origine e la funzione di questo specifica magistratura dai cui atti, conservati presso l’Archivio di Stato di Lucca, si ricavano indicazioni fondamentali sul collezionismo lucchese in età moderna. Riguardo quest’ultimo, mi è parso utile illustrare le origini e le fasi di costituzione di tre delle più importanti raccolte esistenti a Lucca, quelle dei Buonvisi, dei Mansi e dei Conti. In questa sezione, la seconda del lavoro, ho potuto utilizzare i risultati degli studi che, a partire dai contributi di Haskell, sono stati via via compiuti. Così facendo ho cercato di fornire di un contenuto più specifico le indicazioni, a carattere più generale, che ho formulato nella parte precedente. Nella terza sezione ho raccolto le indicazioni ricavate dalla lettura di un numero consistente di inventari, in parte pubblicati (anche se non sempre integralmente), in parte inediti. Riguardo a questi ultimi, li ho rintracciati effettuando una ricerca a largo raggio nel fondo archivistico dei Pubblici Banditori, al quale ho fatto cenno più sopra. Ho compiuto questo lavoro nell’intenzione di redigere una sorta di censimento dei nomi degli artisti lucchesi, attivi tra il Cinquecento e il Settecento, citati nella documentazione. Mi interessava difatti quantificare le presenze di ciascuno di essi allo scopo di intendere in che modo i lucchesi pensavano alla loro specifica tradizione figurativa. Ho raccolto i risultati di questa indagine dedicando a ciascun artista un singolo capitolo nel quale, dopo aver fornito una veloce rassegna delle indicazioni che si ricavano dalle fonti e dall’antica letteratura artistica, ho inserito in ordine cronologico le informazioni che ho recuperato consultando gli inventari. Questo lavoro di verifica e di confronto si è esteso coinvolgendo naturalmente la bibliografia più recente ad essi relativa. Così facendo mi è stato possibile avanzare, in alcuni casi, ipotesi di identificazione delle opere oppure introdurre precisazioni sulle loro vicende collezionistiche

Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo

Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies

Organs on chip approach: A tool to evaluate cancer-immune cells interactions

In this paper we discuss the applicability of numerical descriptors and statistical physics concepts to characterize complex biological systems observed at microscopic level through organ on chip approach. To this end, we employ data collected on a micro uidic platform in which leukocytes can move through suitably built channels toward their target. Leukocyte behavior is recorded by standard time lapse imaging. In particular, we analyze three groups of human peripheral blood mononuclear cells (PBMC): heterozygous mutants (in which only one copy of the FPR1 gene is normal), homozygous mutants (in which both alleles encoding FPR1 are loss-of-function variants) and cells from ‘wild type’ donors (with normal expression of FPR1). We characterize the migration of these cells providing a quantitative con rmation of the essential role of FPR1 in cancer chemotherapy response. Indeed wild type PBMC perform biased random walks toward chemotherapy-treated cancer cells establishing persistent interactions with them. Conversely, heterozygous mutants present a weaker bias in their motion and homozygous mutants perform rather uncorrelated random walks, both failing to engage with their targets. We next focus on wild type cells and study the interactions of leukocytes with cancerous cells developing a novel heuristic procedure, inspired by Lyapunov stability in dynamical systems

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

Effect of electrode distance in grid electrode: Numerical models and in vitro tests

Electrochemotherapy is an emerging local treatment for the management of superficial tumors and, among these, also chest wall recurrences from breast cancer. Generally, the treatment of this peculiar type of tumor requires the coverage of large skin areas. In these cases, electrochemotherapy treatment by means of standard small size needle electrodes (an array of 0.73 cm spaced needles, which covers an area of 1.5 cm2) is time-consuming and can allow an inhomogeneous coverage of the target area. We have previously designed grid devices suitable for treating an area ranging from 12 to 200 cm2. In this study, we propose different approaches to study advantages and drawbacks of a grid device with needles positioned 2 cm apart. The described approach includes a numerical evaluation to estimate electric field intensity, followed by an experimental quantification of electroporation on a cell culture. The electric field generated in a conductive medium has been studied by means of 3-dimensional numerical models with varying needle pair distance from 1 to 2 cm. In particular, the electric field evaluation shows that the electric field intensity with varying needle distance is comparable in the area in the middle of the 2 electrodes. Differently, near needles, the electric field intensity increases with the increasing electrode distance and supply voltage. The computational results have been correlated with experimental ones obtained in vitro on cell culture. In particular, electroporation effect has been assessed on human breast cancer cell line MCF7, cultured in monolayer. The use of 2-cm distant needles, supplied by 2000 V, produced an electroporation effect in the whole area comprised between the electrodes. Areas of cell culture where reversible and irreversible electroporation occurred were identified under microscope by using fluorescent dyes. The coupling of computation and experimental results could be helpful to evaluate the effect of the needle distance on the electric field intensity in cell cultures in terms of reversible or irreversible electroporation

Earthquake characteristics and structural properties of the Southern Tyrrhenian basin from full seismic wave simulations

Modelling the response of seismic wavefields to sharp lateral variations in crustal discontinuities is essential for seismic tomography application and path effects correction in earthquake source characterization. This is particularly relevant when wavefields cross back-arc oceanic basins, i.e. mixed continental-oceanic settings. High-frequency (>0.05 Hz) seismic waves resonate and get absorbed across these settings due to a shallow Moho, crustal heterogeneities, and energy leakage. Here, we provide the first high-frequency wave-equation model of full seismograms propagating through realistic 3D back-arc basins. Inversion by parameters trial based on correlation analyses identifies P-, S- and coda-wave as attributes able to estimate jointly 3D Moho variations, sediment thickness, and earthquake source characteristics using data from a single regional earthquake. We use as data waveforms produced by the Accumoli earthquake (Central Italy, 2016), propagating across the Southern Tyrrhenian basin and recorded across Southern Italy. The best model comprises a deep Moho (∼ 18 km) in the middle of the basin and a crustal pinch with the continental crust in Sicily. The deep Moho corresponds to the Issel Bridge, a portion of continental crust trapped between the Vavilov and Marsili volcanic centres. The Accumoli earthquake is optimally described at a depth of 7.3 km using a boxcar with rise time of 6 s. Our results show that the early S-wave coda comprises trapped and reverberating phases sensitive to crustal interfaces. Forward modelling these waves is computationally expensive; however, adding these attributes to tomographic procedures allows modelling both source and structural parameters across oceanic basins

Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules

Background: Microenvironment cues involved in melanoma progression are largely unknown. Melanoma is highly influenced in its aggressive phenotype by the changes it determinates in its microenvironment, such as pH decrease, in turn influencing cancer cell invasiveness, progression and tissue remodelling through an abundant secretion of exosomes, dictating cancer strategy to the whole host. A role of exosomes in driving melanoma progression under microenvironmental acidity was never described. Methods: We studied four differently staged human melanoma lines, reflecting melanoma progression, under microenvironmental acidic pHs pressure ranging between pH 6.0-6.7. To estimate exosome secretion as a function of tumor stage and environmental pH, we applied a technique to generate native fluorescent exosomes characterized by vesicles integrity, size, density, markers expression, and quantifiable by direct FACS analysis. Functional roles of exosomes were tested in migration and invasion tests. Then we performed a comparative proteomic analysis of acid versus control exosomes to elucidate a specific signature involved in melanoma progression. Results: We found that metastatic melanoma secretes a higher exosome amount than primary melanoma, and that acidic pH increases exosome secretion when melanoma is in an intermediate stage, i.e. metastatic non-invasive. We were thus able to show that acidic pH influences the intercellular cross-talk mediated by exosomes. In fact when exposed to exosomes produced in an acidic medium, pH naïve melanoma cells acquire migratory and invasive capacities likely due to transfer of metastatic exosomal proteins, favoring cell motility and angiogenesis. A Prognoscan-based meta-analysis study of proteins enriched in acidic exosomes, identified 11 genes (HRAS, GANAB, CFL2, HSP90B1, HSP90AB1, GSN, HSPA1L, NRAS, HSPA5, TIMP3, HYOU1), significantly correlating with poor prognosis, whose high expression was in part confirmed in bioptic samples of lymph node metastases. Conclusions: A crucial step of melanoma progression does occur at melanoma intermediate -stage, when extracellular acidic pH induces an abundant release and intra-tumoral uptake of exosomes. Such exosomes are endowed with pro-invasive molecules of clinical relevance, which may provide a signature of melanoma advancement

Machine-Learning for Prescription Patterns: Random Forest in the Prediction of Dose and Number of Antipsychotics Prescribed to People with Schizophrenia

Objective: We aimed to predict antipsychotic prescription patterns for people with schizophrenia using machine learning (ML) algorithms.Methods: In a cross-sectional design, a sample of community mental health service users (SUs; n = 368) with a primary diagnosis of schizophrenia was randomly selected. Socio-demographic and clinical features, including the number, total dose, and route of administration of the antipsychotic treatment were recorded. Information about the number and the length of psychiatric hospitalization was retrieved. Ordinary Least Square (OLS) regression and ML algorithms (i.e., random forest [RF], supported vector machine, K-nearest neighborhood, and Naive Bayes) were used to estimate the predictors of total antipsychotic dosage and prescription of antipsychotic polytherapy (APP).Results: The strongest predictor of the total dose was APP. The number of Community Mental Health Centers (CMHC) contacts was the most important predictor of APP and, with APP omitted, of dosage. Treatment with anticholinergics predicted APP, emphasizing the strong correlation between APP and higher antipsychotic dose. RF performed better than OLS regression and the other ML algorithms in predicting both antipsychotic dose (root square mean error = 0.70, R-2 = 0.31) and APP (area under the receiving operator curve = 0.66, true positive rate = 0.41, and true negative rate = 0.78).Conclusion: APP is associated with the prescription of higher total doses of antipsychotics. Frequent attenders at CMHCs, and SUs recently hospitalized are often treated with APP and higher doses of antipsychotics. Future prospective studies incorporating standardized clinical assessments for both psychopathological severity and treatment efficacy are needed to confirm these findings

ICSBP Is Essential for the Development of Mouse Type I Interferon-producing Cells and for the Generation and Activation of CD8α+ Dendritic Cells

Interferon (IFN) consensus sequence-binding protein (ICSBP) is a transcription factor playing a critical role in the regulation of lineage commitment, especially in myeloid cell differentiation. In this study, we have characterized the phenotype and activation pattern of subsets of dendritic cells (DCs) in ICSBP−/− mice. Remarkably, the recently identified mouse IFN-producing cells (mIPCs) were absent in all lymphoid organs from ICSBP−/− mice, as revealed by lack of CD11clowB220+Ly6C+CD11b− cells. In parallel, CD11c+ cells isolated from ICSBP−/− spleens were unable to produce type I IFNs in response to viral stimulation. ICSBP−/− mice also displayed a marked reduction of the DC subset expressing the CD8α marker (CD8α+ DCs) in spleen, lymph nodes, and thymus. Moreover, ICSBP−/− CD8α+ DCs exhibited a markedly impaired phenotype when compared with WT DCs. They expressed very low levels of costimulatory molecules (intercellular adhesion molecule [ICAM]-1, CD40, CD80, CD86) and of the T cell area-homing chemokine receptor CCR7, whereas they showed higher levels of CCR2 and CCR6, as revealed by reverse transcription PCR. In addition, these cells were unable to undergo full phenotypic activation upon in vitro culture in presence of maturation stimuli such as lipopolysaccharide or poly (I:C), which paralleled with lack of Toll-like receptor (TLR)3 mRNA expression. Finally, cytokine expression pattern was also altered in ICSBP−/− DCs, as they did not express interleukin (IL)-12p40 or IL-15, but they displayed detectable IL-4 mRNA levels. On the whole, these results indicate that ICSBP is a crucial factor in the regulation of two possibly linked processes: (a) the development and activity of mIPCs, whose lack in ICSBP−/− mice may explain their high susceptibility to virus infections; (b) the generation and activation of CD8α+ DCs, whose impairment in ICSBP−/− mice can be responsible for the defective generation of a Th1 type of immune response

Trogocytosis in innate immunity to cancer is an intimate relationship with unexpected outcomes

Trogocytosis is a cellular process whereby a cell acquires a membrane fragment from a donor cell in a contact-dependent manner allowing for the transfer of surface proteins with functional integrity. It is involved in various biological processes, including cell-cell communication, immune regulation, and response to pathogens and cancer cells, with poorly defined molecular mechanisms. With the exception of eosinophils, trogocytosis has been reported in most immune cells and plays diverse roles in the modulation of anti-tumor immune responses. Here, we report that eosinophils acquire membrane fragments from tumor cells early after contact through the CD11b/CD18 integrin complex. We discuss the impact of trogocytosis in innate immune cells on cancer progression in the context of the evidence that eosinophils can engage in trogocytosis with tumor cells. We also discuss shared and cell-specific mechanisms underlying this process based on in silico modeling and provide a hypothetical molecular model for the stabilization of the immunological synapse operating in granulocytes and possibly other innate immune cells that enables trogocytosis