"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

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

Cancer mortality trend in central Italy. focus on a “low rate of land use” area from 1982 to 2011

The aim of the present study was to estimate total cancer mortality trends from 1982 to 2011 in a “low rate of land use” province of the Latium region (Rieti, central Italy) characterized by a low degree of urbanization, a high prevalence of elderly, and a low number of births. Mortality data of the studied period, provided by the Italian National Institute of Statistics, were used for calculating standardized cancer mortality rates. Trends in mortality were analyzed using Joinpoint regression analysis. Results showed that total standardized cancer mortality rates decreased in the monitored area over the study period. A comparison with other provinces of the same region evidenced that the studied province presented the lowest cancer mortality. The three systems/apparatuses affected by cancer that mainly influenced cancer mortality in the monitored province were the trachea-bronchus-lung, colorectal-anus, and stomach. These findings could be attributed to the implement of preventive initiatives performed in the early 2000s, to healthier environmental scenario, and to lower levels of carcinogenic pollutants in air, water, and soil matrices. Thus, our results indicate that the studied area could be considered a “healthy” benchmark for studies in oncological diseases

Opening of the Neo-Tethys Ocean and the Pangea B to Pangea A transformation during the Permian

We studied the stratigraphy, composition, and paleomagnetic properties of lateritic weathering profiles of Permian age from northern Iran and western Karakoram, Pakistan. A limited set of samples deemed representative yielded stable low-inclination paleomagnetic components carried essentially by hematite of chemical origin isolated in massive, fine-grained, and homogeneous ferricrete facies. These laterites originated at equatorial paleolatitudes characterized by intense weathering processes under warm and humid climatic conditions. Paleomagnetic estimates of paleolatitude from Iran, Karakoram, and north Tibet from this study and the literature, albeit sparse, provide testable constraints on the motion of the Cimmerian terranes as the result of the opening of the Neo-Tethys Ocean along the eastern margin of Gondwana during the Permian. We confirm and help refine previous suggestions that the Cimmerian terranes migrated from southern Gondwanan paleolatitudes in the Early Permian to subequatorial paleolatitudes by the Middle Permian – Early Triassic. As a novel conclusion, we find that timing, rates, and geometry of Cimmerian tectonics are broadly compatible with the transformation of Pangea from an Irvingian B to a Wegenerian A-type configuration with Neo-Tethyan opening taking place contemporaneously essentially in the Permian

Cancer-driven dynamics of immune cells in a microfluidic environment

Scope of the present work is to frame into a rigorous, quantitative scaffold - stemmed from stochastic process theory - two sets of experiments designed to infer the spontaneous organization of leukocytes against cancer cells, namely mice splenocytes vs. B16 mouse tumor cells, and embedded in an "ad hoc" microfluidic environment developed on a LabOnChip technology. In the former, splenocytes from knocked out (KO) mice engineered to silence the transcription factor IRF-8, crucial for the development and function of several immune populations, were used. In this case lymphocytes and cancer cells exhibited a poor reciprocal exchange, resulting in the inability of coordinating or mounting an effective immune response against melanoma. In the second class of tests, wild type (WT) splenocytes were able to interact with and to coordinate a response against the tumor cells through physical interaction. The environment where cells moved was built of by two different chambers, containing respectively melanoma cells and splenocytes, connected by capillary migration channels allowing leucocytes to migrate from their chamber toward the melanoma one. We collected and analyzed data on the motility of the cells and found that the first ensemble of IRF-8 KO cells performed pure uncorrelated random walks, while WT splenocytes were able to make singular drifted random walks, that, averaged over the ensemble of cells, collapsed on a straight ballistic motion for the system as a whole. At a finer level of investigation, we found that IRF-8 KO splenocytes moved rather uniformly since their step lengths were exponentially distributed, while WT counterpart displayed a qualitatively broader motion as their step lengths along the direction of the melanoma were log-normally distributed

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

Traffic-related NO2 affects expression of Cupressus sempervirens L. pollen allergens

Traffic pollution has been recognized as directly worsening respiratory symptoms of allergic subjects, although whether urban air pollutants can also directly increase the allergenic potential of pollen has not yet been definitely proven. Therefore, the hypothesis that intra-urban air NO2 variation influences allergens expression in Cupressus sempervirens (Cs) L. pollen was tested.Mature microsporophylls were cut from Cs trees of similar age and height (14-17 m) present in three different sites of Florence (Italy) and processed in the laboratory. Cs pollen allergens amount was determined by a semi-quantitative analysis of electrophoretically separated pollen extracts fractions. NO2 air concentrations were recorded by air monitoring stations located at a distance not exceeding 50 m from each pollen collection site, and the relative annual mean values were acquired by a publicly available database (Tuscan Regional Agency for Environment Protection).Expression of three major Cs pollen allergens was non-linearly correlated with mean annual NO2 concentrations. Expression peak of all major allergens considered was reached at NO2 air concentration (67μg/m3), far below the value at risk for direct effect on the respiratory health (European Union Directive 2008/50/EC).The findings suggest that intra-urban NO2 variations do affect the expression of Cs pollen major allergens, and an apparent low risk NO2 concentration should be regarded as indirectly harmful for increasing the allergenic potential of pollen