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Background A cross-talk between certain oncogenic signaling pathways and PD-L1 expression is emerging. Oncogenic signals often promote cell proliferation, an aggressive cancer hallmark, thus we hypothesized that tumor proliferation rates can influence the levels of PD-L1. Methods We used U251MG and SF767MG glioma cell lines that constitutively express PD-L1 and analyzed the expression level of PD-L1 in condition of serum deprivation and during the phases of cell culture growth. Also, we investigated whether tumor proliferative rates influenced the subcellular distribution of FKBP51s cochaperone, that regulates PD-L1 expression at translational level. Result Our findings suggested that PD-L1 upregulation was associated with DNA synthesis. FKBP51s was detected in ER during DNA replication, but in the nucleus during cell division. A chromatin immunoprecipitation assay using A375-FKBP51 KO melanoma cell line showed that both FKBP51 isoforms can bind the promoter of cyclin D. However, an open chromatin status was found in FKBP51, but FKBP51s enriched chromatin. Conclusion Our study suggests that cell proliferation is an additional factor that drives PD-L1 expression and uncovers an unknown role for its cochaperone that, after assisting PD-L1 production, becomes nuclear in concomitance with the decline of DNA replication and PD-L1 expression.

Melanoma often exploits Treg to avoid immune attack. Treg is a heterogeneous population with respect to immunosuppressive capability. Lymphocytes are particularly rich in FKBP51 (encoded by FKBP5 gene), known as the receptor for FK506. Melanoma aberrantly expresses this protein, which sustains resistance and invasion. Melanoma/immune cell interaction, through PD-L1/PD1, bidirectionally generates FKBP5 splicing inducing a lower molecular weight form termed FKBP51s. In 64 advanced melanoma patient PBMCs, we found that FKBP51s marked a Treg subset that correlated to anti-CTLA4 response. More precisely, a Treg FKBP51s+ count 1.2 and 0.04 and

The present research deals with a preliminary study on two Alexis Harding canvas. The two artworks, belonging to a private collection, consist in glossy paints on aluminum and MDF panel, respectively. In both artworks, the glossy paint is poured on the support, producing a fluid movement on the paint itself. The two artworks, produced in 2003 and in 2008, were exposed in a private house and kept in proper conditions. The first one, Quartet, consist in a yellow and black glossy paint in a flowing movement from the top to the bottom of the canvas. The fluidity is highlighted by a gliding of the paint layer outside the bottom of the canvas itself. Quartet shows a evident alteration, consisting in substantial collapse of the paint layer on the bottom of the canvas. The second canvas, Broken Line, is also painted in yellow and black, but with a different modus operandi. The movement is more fluid, the surface' sagging is less evident and the canvas does not show any evident alterations. The preliminary results here presented concern the study of the materials used by the artist and on the identification of the alteration phenomena. Both the paints were firstly investigated by means of external reflection infrared spectroscopy (ER-FTIR), in order to identify the materials and highlight, where present, possible chemical modifications induced by alteration processes. ER-FTIR has shown the presence of intense and complex C=O signals, suggesting the presence of alkyd paints probably mixed with a lipidic medium, and an inorganic (CO3=) filler. Concerning the Quartet, no evident differences in chemical features were detected between the non-altered and the altered surface. That being so, a micro-sampling campaign was performed to study in detail the nature of the alteration and to describe the alteration processes. ?-ATR confirms the presence of an alkyd paint (alkyd yellow paint by W&N). Further ?-ATR investigations on the cross-section will be presented, in order to understand the sequence of the material used by Harding. The absence of evident chemical modifications of the polymeric paint allow to hypothesize a physical transformation induced by the environmental conditions. In order to investigate on these possible transformations, thermal analysis was also performed

Introduction: In the last years children with chronic hepatitis C (CHC) have been treated with Pegylated Interferon α (PEGIFNα) and ribavirin (RBV). Treatment can cause several side effects that require reduction or interruption of therapy. The relationship between dose of PEG-IFNα and response to therapy has not been clearly evaluated. Aim of this study was to evaluate the impact of the dose of PEG-IFNα2b and RBV on the efficacy of therapy. Patients and method: All children with CHC treated with PEGIFNα2b and RBV, observed at the Paediatric Liver Unit of University Federico II of Naples from 1996 to 2006 were evaluated. Results: Sixteen children with CHC treated with combined therapy were enrolled. Seven out of 16 patients (43.7%) achieved rapid virological response; 13/16 patients (81.2%) achieved early virological response; 5/16 patients (31.25%) relapsed; 1 patient resulted non responder. According to percentage of expected dose, our patients were divided into two groups: the first group included 7 patients that performed an overall dosage of PEG-IFNα2b ≥ 75% of the scheduled full dose; the second group included 9 patients that performedm PEG-IFNα2b dose < 75% of scheduled full dose. No difference was noted in terms of sustained virological response. Conclusion: Modifications of therapy due to PEG-IFNα-related adverse events are frequent in children with CHC, but dose adjustments do not seem to impair efficacy of therapy.

Map of the natural and semi-natural environments and forest types map for the Latium region (Italy). The paper presents the main methodological aspects and the most important results achieved in the implementation of the “Map of natural and semi-natural environments” and of the “Forest types map” in Lazio region at a scale of 1:10.000. The project was carried out for the Agenzia dei Parchi and for the Area Foreste of Regione Lazio through a collaboration between e-GEOS , the University of Rome "La Sapienza", the University of Tuscia and Forestlab Centre , a spin- off of the University of Molise . The project is based on the integrated use of high-resolution satellite imagery and ADS40 false-color infrared digital orthophotos and led to the creation of two maps geometrically and thematically consistent with each other. The “Map of natural and semi-natural environments” is integrated with the pre-existing land use map of the Lazio region deepening the thematic detail up to the 6th Corine level. The “Forest types map” is based on a typological system organized in 17 categories and 36 forest types. L'articolo è disponibile sul sito dell'editore http://www.sisef.it/ forest@/contents/?id=efor1204-011

Early detection and accurate diagnosis of cholestatic jaundice (CJ) are important for successful treatment and favourable prognosis but the rapid and effective recognition of the causes of cholestasis in infants is still challenging also for paediatric gastroenterologist. Here is reported the case of a female infant with CJ who during the observation showed features suggestive of many diseases such as Alagille syndrome, cystic fibrosis, neonatal hemocromatosis, α1-anti-trypsin deficiency (α1-ATD) and biliary atresia. A definite diagnosis was not obtained with a first liver biopsy performed at the age of 58 days which revealed severe lobular hepatitis and signs of cholangitis. An intraoperative cholangiography, performed to exclude biliary atresia, showed signs of sclerosing cholangitis. A second liver biopsy supported diagnosis of sclerosing cholangitis, but also showed signs of α1-ATD. The analysis of phenotype/genotype of α1-ATD excluded this diagnosis. At the end of a challenging diagnostic process, at the age of 75 days, the final diagnosis was of neonatal sclerosing cholangitis, but many doubts persisted. This case confirms that neonatal cholestasis remains a very challenging matter.

Summary Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory effects on cancer cell growth and anti-angiogenetic activity. In the present investigation, we analyzed the inhibitory effects of artemisinin on migratory ability of melanoma cell lines (A375P and A375M, low and medium metastatic properties, respectively). We demonstrate that artemisinin induces cell growth arrest in A375M, and affects A375P cells viability with cytotoxic and growth inhibitory effects, while it was not effective in contrasting proliferation of other tumor cell lines (MCF7 and MKN). In addition, artemisinin affected the migratory ability of A375M cells by reducing metalloproteinase 2 (MMP-2) production and down-regulating αvβ3 integrin expression. These findings introduce a potential of artemisinin as a chemotherapeutic agent in melanoma treatment.

We present a case of a 6 year-old boy with chronic hypertransaminasemia referred to our observation at the age of 17 months, with ALT levels of 2,147 IU/L without signs of cholestasis. Main causes of hypertransaminasemia were excluded and liver biopsy showed chronic hepatitis with minimal activity and moderate portal fibrosis. Therapy with ursodeoxycholic acid (UDCA) was started with a rapid normalization of transaminases. UDCA was suspended in 3 circumstances and in all cases a rapid increase in transaminases was observed. The prompt reinstitution of UDCA was always followed by a rapid normalization of liver enzymes. A defect of bile acid synthesis or conjugation was suspected. Evaluation of urinary biliary acid pattern showed a normal profile on UDCA therapy. Although conjugated biliary acids serum levels were in the normal range, the levels were very low in absence of UDCA therapy and increased in UDCA when transaminases were normal. Therefore, a familial hypercholanemia, with associated defect of the Bile Acid CoA: amino acid N-acyltransferase (BAAT) was suspected. At present this hypothesis is under investigation. Even if the diagnosis is not still confirmed, this case suggests the disorder as possible cause of hypertransaminasemia not associated with signs of cholestasis.