Recognition mechanism of p63 by the E3 ligase Itch Novel strategy in the study and inhibition of this interaction.

The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer’s or Huntington’s diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly 13C-15N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534–551 residue of p63, encompassing the PP xY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PP xY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase

Allyl sulfur compounds and cellular detoxification system: effects and perspectives in cancer therapy

Natural organosulfur compounds (OSCs) have been shown to have chemopreventive effects and to suppress the proliferation of tumor cells in vitro through the induction of apoptosis. The biochemical mechanisms underlying the antitumorigenic and anti-proliferative effects of garlic-derived OSCs are not fully understood. Several modes of action of these compounds have been proposed, and it seems likely that the rate of clearance of allyl sulfur groups from cells is a determinant of the overall response. The aim of this review is to focus attention on the effects of natural allyl sulfur compounds on the cell detoxification system in normal and tumor cells. It has been already reported that several natural allyl sulfur compounds induce chemopreventive effects by affecting xenobiotic metabolizing enzymes and inducing their down-activation. Moreover, different effects of water- and oil-soluble allyl sulfur compounds on enzymes involved in the detoxification system of rat tissues have been observed. A direct interaction of the garlic allyl sulfur compounds with proteins involved in the detoxification system was studied in order to support the hypothesis that proteins possessing reactive thiol groups and that are involved in the detoxification system and in the cellular redox homeostasis, are likely the preferential targets of these compounds. The biochemical transformation of the OSCs in the cell and their adducts with thiol functional groups of these proteins, could be considered relevant events to uncover the anticancer properties of the allyl sulfur compounds. Although additional studies, using proteomic approaches and transgenic models, are needed to identify the molecular targets and modes of action of these natural compounds, the allyl sulfur compounds can represent potential ideal agents in anticancer therapy, either alone or in association with other antitumor drugs

Photo-polymerization damage protection by hydrogen sulfide donors for 3d-cell culture systems optimization

Photo-polymerized hydrogels are ideally suited for stem-cell based tissue regeneration and three dimensional (3D) bioprinting because they can be highly biocompatible, injectable, easy to use, and their mechanical and physical properties can be controlled. However, photo-polymerization involves the use of potentially toxic photo-initiators, exposure to ultraviolet light radiation, formation of free radicals that trigger the cross-linking reaction, and other events whose effects on cells are not yet fully understood. The purpose of this study was to examine the effects of hydrogen sulfide (H2S) in mitigating cellular toxicity of photo-polymerization caused to resident cells during the process of hydrogel formation. H2S, which is the latest discovered member of the gasotransmitter family of gaseous signalling molecules, has a number of established beneficial properties, including cell protection from oxidative damage both directly (by acting as a scavenger molecule) and indirectly (by inducing the expression of anti-oxidant proteins in the cell). Cells were exposed to slow release H2S treatment using pre-conditioning with glutathione-conjugated-garlic extract in order to mitigate toxicity during the photo-polymerization process of hydrogel formation. The protective effects of the H2S treatment were evaluated in both an enzymatic model and a 3D cell culture system using cell viability as a quantitative indicator. The protective effect of H2S treatment of cells is a promising approach to enhance cell survival in tissue engineering applications requiring photo-polymerized hydrogel scaffolds

Overview and Status of Thermophotovoltaic Systems

Abstract In the last decade thermophotovoltaic (TPV) generator has gained an increasing attention as cogeneration system for the distributed generation sector. Nevertheless, these systems are not fully developed and studied: several aspects need to be further investigated and completely understood. The aim of this study is to give a complete overview and the status of the art of thermophotovoltaic generation considering both the research developments and the experiences field. More in details, in this study, the characteristics of a TPV generator are analyzed with a particular attention to the physical relationships which govern the behavior of its main components. Moreover, the current technologies regarding the combustor, the emitter, the optical filter and the photovoltaic cells are investigated by taking into account both the role of each component and also their integration in the whole system. Finally, a critical review of the realized prototypes is presented and discussed

Storage Solutions for Renewable Production in Household Sector

Abstract The penetration of renewable sources, particularly wind and solar, into the grid has been increasing in recent years. As a consequence, there have been serious concerns over reliable and safety operation of power systems. One possible solution, to improve grid stability, is to integrate energy storage devices into power system network: storing energy produced in periods of low demand to later use, ensuring full exploitation of intermittent available sources. Focusing on stand-alone photovoltaic (PV) energy system, energy storage is needed with the purpose of ensuring continuous power flow, to minimize or, if anything, to neglect electrical grid supply. A comprehensive study on a hybrid stand-alone photovoltaic power system using two different energy storage technologies has been performed. This study examines the feasibility of replacing electricity provided by the grid with hybrid system to meet household demand. This paper is a part of an experimental and a theoretical study which is currently under development at University of Bologna. A test facility is under construction, at the University of Bologna, for the experimental characterization of the cogenerative performance of small scale hybrid power systems, composed of micro-CHP systems of different technologies : a Micro Rankine Cycles (MRC), a Proton Exchange Membrane Fuel Cells (PEM-FC), a battery, an electrolyzer and a heat recovery subsystem. The test set-up is also integrated with an external load simulator, in order to generate variable load profiles. This paper presents the theoretical results of the performance simulations developed considering an hybrid system consisting on a photovoltaic array (PV), electrochemical batteries (B) and electrolyzer (HY) with a H2 tank and a Proton Exchange Membrane Fuel Cell (PEM-FC) stack, in case of a household electrical demand. The performance of this system have been evaluated by the use of a calculation code, in-house developed by University of Bologna; future activities will be the tuning of the software with the experimental results, in order to realize a code able to define the correct size of each sub-system, ones the load profile of the utility is known or estimated

Ascorbate metabolism and the developmental demand for tartaric and oxalic acids in ripening grape berries

Background. Fresh fruits are well accepted as a good source of the dietary antioxidant ascorbic acid (Asc, Vitamin C). However, fruits such as grapes do not accumulate exceptionally high quantities of Asc. Grapes, unlike most other cultivated fruits do however use Asc as a precursor for the synthesis of both oxalic (OA) and tartaric acids (TA). TA is a commercially important product in the wine industry and due to its acidifying effect on crushed juice it can influence the organoleptic properties of the wine. Despite the interest in Asc accumulation in fruits, little is known about the mechanisms whereby Asc concentration is regulated. The purpose of this study was to gain insights into Asc metabolism in wine grapes (Vitis vinifera c.v. Shiraz.) and thus ascertain whether the developmental demand for TA and OA synthesis influences Asc accumulation in the berry. Results. We provide evidence for developmentally differentiated up-regulation of Asc biosynthetic pathways and subsequent fluctuations in Asc, TA and OA accumulation. Rapid accumulation of Asc and a low Asc to dehydroascorbate (DHA) ratio in young berries was co-ordinated with up-regulation of three of the primary Asc biosynthetic (Smirnoff-Wheeler) pathway genes. Immature berries synthesised Asc in-situ from the primary pathway precursors D-mannose and L-galactose. Immature berries also accumulated TA in early berry development in co-ordination with up-regulation of a TA biosynthetic gene. In contrast, ripe berries have up-regulated expression of the alternative Asc biosynthetic pathway gene D-galacturonic acid reductase with only residual expression of Smirnoff-Wheeler Asc biosynthetic pathway genes and of the TA biosynthetic gene. The ripening phase was further associated with up-regulation of Asc recycling genes, a secondary phase of increased accumulation of Asc and an increase in the Asc to DHA ratio. Conclusion. We demonstrate strong developmental regulation of Asc biosynthetic, recycling and catabolic genes in grape berries. Integration of the transcript, radiotracer and metabolite data demonstrates that Asc and TA metabolism are developmentally regulated in grapevines; resulting in low accumulated levels of the biosynthetic intermediate Asc, and high accumulated levels of the metabolic end-product TA

Performance Increase of a Small-scale Liquefied Natural Gas Production Process by Means of Turbo-expander☆

Abstract In the last years, the growing demand of the energy market has led to the increasing penetration of renewable energy sources in order to achieve the primary energy supply. However, in the next years fossil fuels are expected to remain the dominant energy source, due to the forecasted increase of global energy consumption. In particular, the natural gas is predicted to still play a key role in the energy market, on account of its lower environmental impact than other fossil fuels. Natural gas is currently employed mainly as gaseous fuel for stationary energy generation, but also as liquefied fuel, as an alternative to the diesel fuel, in vehicular applications. Liquefied Natural Gas (LNG) is currently produced in large plants directly located at the extraction sites. The aim of the study is the definition of an optimal small-scale production process for LNG, to be realized – in opposition to the current habit – directly at filling stations. With this purpose, two different LNG production layouts have been proposed and investigated within a thermodynamic analysis: starting from a Joule-Thompson LNG expansion process, a new layout with a turbo-expander has been proposed for the natural gas liquefaction. The carried-out simulations show that the new proposed solution allow to optimize the LNG production process and to minimize the process' energy consumption

Hydrogen sulfide as potential regulatory gasotransmitter in arthritic diseases

The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H2S) were recently demonstrated in the context of different inflammatory diseases. In particular, H2S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H2S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H2S, more evidence is needed to understand the pathophysiology and the potential of H2S as a therapeutic agent. Within this review, we provide an overview on H2S biological effects, on its role in immune-mediated inflammatory diseases, on H2S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases

energetic and economic analysis of a new concept of solar concentrator for residential application

Abstract Renewable energy penetration is increasing in last years, covering a more and more important role in both electrical and thermal supply. Nowadays, the photovoltaic conversion is a consolidated technology and can be efficiently combined with solar concentration. In this study, a new concept of photovoltaic solar concentrator based on non-conventional mirrors coupled with high efficiency triple-junctions cells is described and discussed. More in details, as for the optical design, deformations are applied to classical spherical mirrors to control solar aberrations and boost efficiency of a receiver consisting in a dense array of cells. The efficiency enhance is obtained by high matching between the collected solar irradiance and the receiver electrical features. The concentrator is able to produce both electrical and thermal energy: the system requires in fact an active cooling circuit to maintain the cells performance. This behavior makes the system suitable for combined heat and power applications with particular reference to high direct irradiance environments. An analytical study, considering a residential utility has been performed in order to understand the energetic and economic performance of the system. In particular, a simulation has been carried out by the use of an in-house-developed calculation code considering a whole year of operation

Optimum sizing of cogeneration plants by means of a genetic algorithm optimization: A case study

In the context of increasing energy consumption, multi-generation systems such as combined heat and power generation (CHP) are attractive to meet the increasingly stringent requirements regarding energy saving in buildings. Hospitals are great consumers of energy, both electrical and thermal: the use of heating and cooling equipment for maintaining satisfactory comfort and indoor air quality for the patients as well as the adoption of several electrical health equipment result in the highest energy consumption per unit floor area of the entire building sector. In the present study, co/tri-generation systems\u2019 optimal set-up, size and operation are investigated for small/medium size hospital facilities. More specifically, after the presentation of the energy consumption profiles for a medium size hospital with 600 beds, set as reference case for this study, a parametric analysis has been carried out varying the peak loads of the user. For each of the proposed scenarios, the optimal plant configuration (sizing of all the energy production systems) has been outlined by means of a numerical code (Trigen 3.0) in-house developed. Afterwards, in order to optimize the load distribution in a smart grid characterized by electrical, thermal, cooling and fuel energy fluxes, an ulterior numerical investigation has been performed. The software, named EGO (Energy Grids Optimizer) consists of a genetic algorithm procedure: it defines the optimal load distribution of a number of energy systems operating into a smart grid based on the minimization of an objective function which expresses the total cost of energy production. Finally, an economic analysis has been carried out in order to evaluate the profitability of the proposed CHP-heat pump scenario