Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein

To bring insights into neurofibroma biochemistry, a comprehensive secretome analysis was performed on cultured human primary Schwann cells isolated from surgically resected plexiform neurofibroma and from normal nerve tissue. Using a combination of SDS-PAGE and high precision LC-MS/MS, 907 proteins were confidently identified in the conditioned media of Schwann cell cultures combined. Label free proteome profiling revealed consistent release of high levels of 22 proteins by the four biological replicates of NF1 Schwann cell cultures relative to the two normal Schwann cell cultures. Inversely, 9 proteins displayed decreased levels in the conditioned media of NF1 relative to normal Schwann cells. The proteins with increased levels included proteins involved in cell growth, angiogenesis and complement pathway while proteins with decreased levels included those involved in cell adhesion, plasminogen pathway and extracellular matrix remodeling. Retinoic acid receptor responder protein-1 (RARRES1), previously described as an integral membrane tumor suppressor, was found exclusively secreted by NF1 Schwann cells but not by normal Schwann cells. All-trans retinoic acid modulated secretion of RARRES1 in a dose dependent manner. This study shows altered secretion of key proteins in NF1 derived Schwann cells. The potential implication of these proteins in neurofibroma biology is discussed.     

Biosurfactants from Urban Wastes for Detergent Formulation: Surface Activity and Washing Performance

To promote biobased products for industry, six biosurfactants (BS) isolated from green and food urban residues aged under aerobic digestion for 0–60 days were investigated for their chemical composition, surface activity properties and detergent performance in fabric washing in comparison with commercial anionic and nonionic surfactants (CS). The BS exhibited a range of chemical composition and surface activity properties presumably related to their different biomass sources. Surface tension data for these substances correlated meaningfully with performance data in fabric washing. It was found that BS have similar performances as CS when used neat, but the 1:1 w/w BS–CS mixes are characterized by significant synergy. High sensitivity to water hardness and fabric yellowing were found to be the main deficiencies for the BS. However, both effects are minimized or are not critically evident when the BS are used together with CS and/or in common detergents formulations. The results indicate that when used above critical micellar concentration, no significant or critical performance differences are evident within the whole group of BS or between BS and CS. These facts encourage expectations for industrial production and real commercialization of BS as components of detergents formulations.     

Evaluation of 4-(4-Fluorobenzyl)piperazin-1-yl]-Based Compounds as Competitive Tyrosinase Inhibitors Endowed with Antimelanogenic Effects

There is a considerable attention for the development of inhibitors of tyrosinase (TYR) as therapeutic strategy for the treatment of hyperpigmentation disorders in humans. Continuing in our efforts to identify TYR inhibitors, we describe the design, synthesis and pharmacophore exploration of new small molecules structurally characterized by the presence of the 4-fluorobenzylpiperazine moiety as key pharmacophoric feature for the inhibition of TYR from Agaricus bisporus (AbTYR). Our investigations resulted in the discovery of the competitive inhibitor [4-(4-fluorobenzyl)piperazin-1-yl]-(3-chloro-2-nitro-phenyl)methanone 26 (IC₅₀=0.18 μM) that proved to be ∼100-fold more active than reference compound kojic acid (IC₅₀=17.76 μM). Notably, compound 26 exerted antimelanogenic effect on B16F10 cells in absence of cytotoxicity. Docking analysis suggested its binding mode into AbTYR and into modelled human TYR.     

Structural and Functional Characterization of the ABCC6 Transporter in Hepatic Cells: Role on PXE,Cancer Therapy and Drug Resistance

Pseudoxanthoma elasticum (PXE) is a complex autosomal recessive disease caused by mutations of ABCC6 transporter and characterized by ectopic mineralization of soft connective tissues. Compared to the other ABC transporters, very few studies are available to explain the structural components and working of a full ABCC6 transporter, which may provide some idea about its physiological role in humans. Some studies suggest that mutations of ABCC6 in the liver lead to a decrease in some circulating factor and indicate that PXE is a metabolic disease. It has been reported that ABCC6 mediates the efflux of ATP, which is hydrolyzed in PPi and AMP; in the extracellular milieu, PPi gives potent anti-mineralization effect, whereas AMP is hydrolyzed to Pi and adenosine which affects some cellular properties by modulating the purinergic pathway. Structural and functional studies have demonstrated that silencing or inhibition of ABCC6 with probenecid changed the expression of several genes and proteins such as NT5E and TNAP, as well as Lamin, and CDK1, which are involved in cell motility and cell cycle. Furthermore, a change in cytoskeleton rearrangement and decreased motility of HepG2 cells makes ABCC6 a potential target for anti-cancer therapy. Collectively, these findings suggested that ABCC6 transporter performs functions that modify both the external and internal compartments of the cells.     

BRAF Gene and Melanoma: Back to the Future

As widely acknowledged, 40–50% of all melanoma patients harbour an activating BRAF mutation (mostly BRAF V600E). The identification of the RAS–RAF–MEK–ERK (MAP kinase) signalling pathway and its targeting has represented a valuable milestone for the advanced and, more recently, for the completely resected stage III and IV melanoma therapy management. However, despite progress in BRAF-mutant melanoma treatment, the two different approaches approved so far for metastatic disease, immunotherapy and BRAF+MEK inhibitors, allow a 5-year survival of no more than 60%, and most patients relapse during treatment due to acquired mechanisms of resistance. Deep insight into BRAF gene biology is fundamental to describe the acquired resistance mechanisms (primary and secondary) and to understand the molecular pathways that are now being investigated in preclinical and clinical studies with the aim of improving outcomes in BRAF-mutant patients.     

On road experimental tests of hydrogen/natural gas blends on transit buses

The promise of reducing harmful and CO₂ emissions by focusing on hydrogen-methane blends (HCNG) have recently attracted the interest of vehicle manufacturers and transport operators. Several experiments have been conducted in laboratory facilities to assess the potential of HCNG blends in order to decrease the exhaust emissions. This paper reports the results of experimental tests performed at the ENEA Casaccia Research Center aiming to evaluate the energy and environmental performances of a CNG vehicle when fuelled with a hydrogen-methane blend. Two buses for urban transit service were fuelled with HCNG blends with different percentage of hydrogen (5%, 10%, 15%, 20% and 25% of hydrogen by volume). A 100% methane gas was used as reference to compare the advantages and disadvantages that can be derived from the use of HCNG blends. Road tests have been carried out by running fixed tracks, which are representative of urban and suburban driving cycles. Vehicles were powered with a lean burn engine whose setup - based on ignition advance angle, has been tuned for controlling the NO_x emissions. CO₂ emissions have been investigated to evaluate the leverage effect based on an increased CO₂ reduction resulting from an increased engine efficiency.     

Evaluation of Reliability Indicators for WDNs with Demand-Driven and Pressure-Driven Models

Reliability of water distribution networks (WDNs) has received much attention in recent years due to progressive aging of infrastructures and climate change. Several reliability indicators, focusing on hydraulic aspects rather than water quality, have been proposed in literature. Reliability is generally assessed resorting to well established methods coupling hydraulic simulations and stochastic techniques that describe the WDNs hydraulic performance and component availability respectively. Two main algorithms are employed to simulate WDNs: the demand driven approach (DDA) that disregards the physical relationship between actual water demand and nodal pressure, and the pressure driven approach (PDA) that explicitly incorporates it. In this paper, we show how the choice of hydraulic solver may affect reliability indicators. We modify existing quantitative indicators at nodal and network level, and define novel indicators to consider water quality aspects. These indicators are evaluated for three example WDNs; discrepancies between results obtained with the two approaches depend on network size, feeding scheme and skeletonization. Results suggest to use with caution the DDA for reliability assessment at both local and global level.     

Manufacturing of polypropylene laminates and related structural reorganization in the crystalline phase

The conditions for obtaining recrystallization in more ordered modifications are described for an uniaxially oriented sample of isotactic polypropylene, annealed with fixed ends. These recrystallization conditions are related to the conditions of a lamination process.     

Hydrogen sorption sites in the gallium containing hybrid catalysts used for the aromatization of light alkanes

Gallium species which were incorporated initially in the oxide form, were all in the (+3) oxidation state in the hybrid catalyst and exhibited two types of hydrogen chemisorption sites, s_hw and s_hs. The stronger sorption sites shs which predominated at higher gallium dispersion, corresponded probably to the most effective surface configuration for gallium in the aromatization ofn-butane.     

Reduced graphene oxide-ZnO hybrid composites as photocatalysts: The role of nature of the molecular target in catalytic performance

Spurred by controversial literature findings, we enwrapped reduced graphene oxide (rGO) in ZnO hierarchical microstructures (rGO loadings spanning from 0.01 to 2 wt%) using an in situ synthetic procedure. The obtained hybrid composites were carefully characterized, aiming at shining light on the possible role of rGO on the claimed increased performance as photocatalysts. Several characterization tools were exploited to unveil the effect exerted by rGO, including steady state and time resolved photoluminescence, electron microscopies and electrochemical techniques, in order to evaluate the physical, optical and electrical features involved in determining the catalytic degradation of rhodamine B and phenol in water.Several properties of native ZnO structures were found changed upon the rGO enwrapping (including optical absorbance, concentration of native defects in the ZnO matrix and double-layer capacitance), which are all involved in determining the photocatalytic performance of the hybrid composites. The findings discussed in the present work highlight the high complexity of the field of application of graphene-derivatives as supporters of semiconducting metal oxides functionality, which has to be analyzed through a multi-parametric approach.