DENDRITIC CELL DIFFERENTIATION BLOCKED BY PRIMARY EFFUSION LYMPHOMA-RELEASED FACTORS IS PARTIALLY RESTORED BY INHIBITION OF P38 MAPK

To better understand the molecular mechanisms underlying the dendritic cell (DC) defects in cancer, we analyzed which signaling pathway is implicated in the abnormal monocyte differentiation into DC determined by the presence of Primary effusion lymphoma (PEL) released factors. Our results indicate that the DC, obtained in this condition, together with phenotypic abnormalities and reduced allostimulatory function, showed hyperphosphorylation of signal transducer and activator of transcription 3 (STAT3) and p38 mitogen-activated protein kinase (MAPK) molecules, in comparison to the DC differentiated in the absence of PEL-released factors. The inhibition of p38 MAPK but not of STAT3 phosphorylation, with specific inhibitors, was able to revert the effect of the PEL-released factors on the DC phenotype. This study suggests that p38 MAPK signaling pathway is an important contributor to the abnormal differentiation of DC in PEL

Chloroquine supplementation increases the cytotoxic effect of curcumin against Her2/neu overexpressing breast cancer cells in vitro and in vivo in nude mice while counteracts it in immune competent mice

Autophagy is usually a pro-survival mechanism in cancer cells, especially in the course of chemotherapy, thus autophagy inhibition may enhance the chemotherapy-mediated anti-cancer effect. However, since autophagy is strongly involved in the immunogenicity of cell death by promoting ATP release, its inhibition may reduce the immune response against tumors, negatively influencing the overall outcome of chemotherapy. In this study, we evaluated the in vitro and in vivo anti-cancer effect of curcumin (CUR) against Her2/neu overexpressing breast cancer cells (TUBO) in the presence or in the absence of the autophagy inhibitor chloroquine (CQ). We found that TUBO cell death induced by CUR was increased in vitro by CQ and slightly in vivo in nude mice. Conversely, CQ counteracted the Cur cytotoxic effect in immune competent mice, as demonstrated by the lack of in vivo tumor regression and the reduction of overall mice survival as compared with CUR-treated mice. Immunohistochemistry analysis revealed the presence of a remarkable FoxP3 T cell infiltrate within the tumors in CUR/CQ treated mice and a reduction of T cytotoxic cells, as compared with single CUR treatment. These findings suggest that autophagy is important to elicit anti-tumor immune response and that autophagy inhibition by CQ reduces such response also by recruiting T regulatory (Treg) cells in the tumor microenvironment that may be pro-tumorigenic and might counteract CUR-mediated anti-cancer effects

Harbour water managment for port structures and sea bottom design, coast proximity navigation managment, water quality control.

Tide is a sea level up-down water motion basically depending on three different phenomena: the Earth-Moon-Sun gravitational relationship, the water surface fluid reaction to atmospheric meteorological dynamic action and the Newtonian vertical adjustment of the sea surface due to atmospheric pressure variations. The first tide component (astro-tide) is periodic and well known in all points of the Earth surface; the second one is directly related to the meteorological phenomenon and then it is foreseeable; the Newtonian component, on the contrary, is not readily predictable by a general hydrostatic law, because the factor “J” that represents the Newtonian transfer (from the atmospheric weight to the consequent sea level) is variable in each harbour area. A statistical study and the related numerical data interpretation of the measurements performed in the Ports of Genoa, La Spezia, Marina di Carrara, Livorno, Piombino, Civitavecchia and Ravenna (belonging to the Italian Newtonian Meteotide Network) show port values of Jph (from 1.4-1.6 cm/hPa to > 2 cm/hPa, on the contrary of the off-shore areas where Jph is about 1 cm/hPa). This phenomenon (hydrobarometric tide wave) produces even double values of harbour sea level fluctuations amplitude in comparison to astronomic tide sea level oscillations, and is characterized by a wavelength from 8-12 h to same days and a 10-25 days/year as mean temporal occurrence in the Northern Tyrrhenian Sea. This is the most relevant ordinary risk factor for our ports activity and structures design. The present note shows a quantitative method to define the values of Jph factor for ports and its use in the Harbour WaterSide Management (HWSM) based on the joined use of barometers, hydrometers and clocks, the preliminary results related to the use of the gravimeters as hydrobarometric predictor in La Spezia Port and two examples of use of Jph factor in the port management: refloating of a landing ship and optimisation of a dock performance as pleasure boats mooring

Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes

BACKGROUND: Monocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc. METHODS: Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells. RESULTS: Infectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes. CONCLUSION: This study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells

Targeting COX-2/PGE(2) pathway in HIPK2 knockdown cancer cells: impact on dendritic cell maturation.

production after HIPK2 depletion and how to modulate it./VEGF production. At translational level, while conditioned media of both siRNA control and HIPK2 depleted cells inhibited DCs maturation, conditioned media of only zinc-treated HIPK2 depleted cells efficiently restored DCs maturation, seen as the expression of co-stimulatory molecules CD80 and CD86, cytokine IL-10 release, and STAT3 phosphorylation./VEGF production; and 3) zinc treatment of HIPK2 depleted cells restored DCs maturation

The newtonian approach in the meteorological tide waves forecasting: preliminary observations in the East Ligurian harbours

Sea level oscillations are the superposition of many contributions, among which the main are astronomic and meteorological low-frequency tides. In Ligurian Sea meteo-tide components, being most ample than astronomic fluctuations, drive water exchange in harbours. The present note shows first results about port of Genoa concerning a coherency study between atmospheric variation and corresponding sea level adjustment (meteorological tide). The newtonian forecasting method of meteorological tides is based on measurements of time elapsing between barometric sea level unbalance (Δg) and its meteorological tide compensation (inverse barometer component). Meteorological tide component is independent on the Earth-Moon-Sun gravitational relationships, moreover parameters related to the shifted water mass are too many to describe the phenomenon analytically (basin topography, barometric strength position and time, chemical water quality, off-shore sea circulation, etc.); then, meteorological tide can’t be accurately foreseen by atmospheric pressure measurements only. A gravimeter can detect the geodetic unbalance starting time and a tide-gauge can detect the newtonian compensation (tide wave) coming time. The difference between these two times is the meteorological tide delay. An opportune statistic of this delay provides an experimental law typical for each harbour to forecast the meteo-tide compensation wave delay. This paper describes the methodological procedure adopted and first evidences of the phenomenon in Genoa harbour

Sistema per l'acquisizione e la trasmissione dei dati della stazione mareografica MENFOR

Il presente documento descrive i componenti e le funzionalità del sistema realizzato per l’acquisizione e la trasmissione dei dati della stazione mareografica MENFOR sviluppata nell’ambito del progetto “Sviluppo di una stazione portuale per la previsione dei flussi di marea meteorologica, finalizzata a costituire un servizio per la sicurezza della navigazione e per la protezione dei natanti nel Golfo della Spezia” supportato dal programma PRAI-FESR della Regione Liguria. Il sistema qui descritto è stato realizzato con il contributo di tutti gli Enti coinvolti

Multislice computed tomography SYNTAX score for coronary artery disease evaluation prior to transcatheter aortic valve implantation

Background: Coronary computed tomography angiography (CCTA) is a useful tool for the evaluation of coronary anatomy prior to both surgical and transcatheter aortic valve implantation (TAVI). Multislice Computed Tomography (MSCT) SYNTAX score (SXscore) strongly correlates with the traditional angiographic SXscore, and the latter has proven to predict cardiovascular events in patients with coronary artery disease (CAD) referred to TAVI. Purpose: The aim of the study is to evaluate the feasibility and accuracy of the calculation of MSCT SXscore in TAVI patients, compared to the gold standard angiographic SXscore. Materials and methods: We evaluated 65 patients eligible for TAVI who underwent both CCTA and invasive coronary angiography (ICA) prior to valve replacement. CCTA was compared to ICA in terms of sensitivity, specificity, and positive and negative predictive values. CCTA performance was evaluated at 3 levels: patient level, vessellevel and segmentlevel. MSCT SXscore was calculated, when possible (i.e. only in fullyevaluable scans), and compared to the angiographic SXscore. Results: Overall CCTA diagnostic performance was good, with high sensitivity and negative predictive values (97.2% and 96.0%, respectively) and good agreement with ICA (k=0.81). As expected, specificity and positive predictive values were lower (82.8% and 87.5%, respectively). At vessellevel, the circumflex artery (CA) was more often misdiagnosed than the other arteries. We were able to calculate MSCT SXscore in 50/65 scans (76.9%). The correlation between MSCT and angiographic SXscore was excellent (Pearson's R=0.965, P<0.001). Conclusions: MSCT SXscore emerges as an interesting tool with strong agreement with angiographic SXscore, providing a noninvasive ambulatory alternative to assess CAD severity in TAVI patients

SCAI-r: an algorithm for obtaining synoptic and spatial atmospheric parameters.

Abstract: The highest performance of multiband optical data (Visible - VIS ? Shortwave Infrared - SWIR ? (400-2500 nm) (e.g. imaging spectroscopy approaches) can be reached mainly through atmospheric correction effects; the conversion of the image values to surface reflectance, allowing, for instance, to estimate the amount of biochemical compounds in the target. This work aims to present an algorithm dedicated to atmospheric parameters obtaining from MODIS and related sensors, encapsulated in a user-friendly interface through Software to Collect Atmospheric Information (SCAI-r), applied to the correction of atmosphere effects on Rapideye image. The results show that SCAI-r generates information needed to perform atmospheric correction and that it has a greater influence over water-related objects, when compared to parameters randomly inserted as input data in atmospheric correction algorithms