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

Can COVID-19 pandemic boost the epidemic of neurodegenerative diseases?

The pandemic of Coronavirus Disease 2019 (COVID-19) presents the world with the medical challenge associated with multifactorial nature of this pathology. Indeed COVID-19 affects several organs and systems and presents diversified clinical picture. COVID-19 affects the brain in many ways including direct infection of neural cells with SARS-CoV-2, severe systemic inflammation which floods the brain with pro-inflammatory agents thus damaging nervous cells, global brain ischaemia linked to a respiratory failure, thromboembolic strokes related to increased intravascular clotting and severe psychological stress. Often the COVID-19 is manifested by neurological and neuropsychiatric symptoms that include dizziness, disturbed sleep, cognitive deficits, delirium, hallucinations and depression. All these indicate the damage to the nervous tissue which may substantially increase the incidence of neurodegenerative diseases and promote dementia

Cell death in disease: from 2010 onwards

The strong interest in cell death, and the shift in emphasis from basic mechanisms to translational aspects fostered the launch last year of the new sister journal of Cell Death and Differentiation, named Cell Death and Disease, to reflect its stronger focus towards clinical applications. Here, we review that first year of activity, which reflects an enthusiastic response by the scientific community. On the basis of this, we now launch two novel initiatives, the start of a new section dedicated to cancer metabolism and the opening of a new editorial office in Shanghai

Cell death pathology: Cross-talk with autophagy and its clinical implications

AbstractAutophagy is a self-digesting mechanism that cells adopt to respond to stressful stimuli. Morphologically, cells dying by autophagy show multiple cytoplasmic double-membraned vacuoles, and, if prolonged, autophagy can lead to cell death, "autophagic cell death". Thus, autophagy can act both as a temporary protective mechanism during a brief stressful episode and be a mode of cell death in its own right. In this mini-review we focus on recent knowledge concerning the connection between autophagy and programmed cell death, evaluating their possible implications for therapy in pathologies like cancer and neurodegeneration

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

Smart District Heating: Distributed Generation Systems' Effects on the Network☆

Abstract The European strategy 20-20-20 – providing for energy efficiency increase, pollutant emissions reduction and fossil fuel consumption reduction – leads to an increasing attention on the concept of smart cities. In this scenario, it is important to consider a possible integration between networks and distributed generation systems – i.e. to realize a bidirectional energy flux at the utilities, giving rise to the so-called smart grid – not only for the electrical sector, but also for the thermal energy field. Therefore, the concept of smart grid could be extended to the heat sector in relation to District Heating Networks (DHNs) and considering thermal energy distributed generation systems, such as solar thermal panels or micro-Combined Heat and Power (micro-CHP) generators. In this study several different layouts for the utilities substations in smart DHNs will be presented and discussed. These layouts have been developed in order to allow the bidirectional exchange of thermal energy at the utilities, optimizing the thermal exchange as function of network design temperatures (for both the supply and the return), of utilities' thermal power requirement and depending on the characteristics of the production system. Further, in this paper the results obtained from the simulations, carried out with the software Intelligent Heat Energy Network Analysis (I.H.E.N.A.) considering the implementation of the elaborated layouts, will be analyzed

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

Thermodynamic Evaluation of Repowering Options for a Small-size Combined Cycle with Concentrating Solar Power Technology☆

Abstract The increasing penetration of low-carbon technologies and enhancements in fossil-fuelled power plants efficiency are some of the most important and up to date research topics. Renewable energy, in particular solar, has the potential of meeting the world energy needs while addressing environmental concerns, but technological advances in renewable energy electricity production are necessary to become competitive with conventional technologies. New opportunities to increase the penetration of renewables energies, smoothing out renewables variability and intermittency problems, come out from the hybridization concept. Hybrid renewable-fossil fuel systems join the advantages of both renewable energies and programmable devices. Among all the renewable technologies available for hybridization, Concentrating Solar Power (CSP) with parabolic trough is the most diffused because of its relatively conventional technology and ease of scale-up. CSP hybrids are well established worldwide, predominantly with natural gas: the hybridization options for CSP ranging from feed water heating, reheat steam, live steam to steam superheating. Based on a detailed thermodynamic cycle model of a reference small-size one pressure level Combined Cycle (CC) plant, the impact of CSP addition is thoroughly evaluated. Different hybrid schemes are evaluated and compared considering CC off-design operation. The goal of this study is to evaluate, from a thermodynamic point of view, three repowering options of a small-size CC with a CSP system in a hybrid system configuration and to quantify their potential benefits in terms of system's performance increase. In particular, the optimal size of CSP plant is shown for each investigated hybrid repowering options. The changes in CC steam cycle operating parameters are presented together with CC performance increase. It is shown that solar hybridization into an existing CC plant may give rise to a substantial benefit from a thermodynamic point of view

Complex energy networks: Energy-ecological efficiency based evaluations towards the sustainability in energy sector

In the last years, international programs in diverse sectors and national frameworks have been driven by the need of a sustainable growth, in a green economy perspective. In order to reduce the energy losses/dissipations, as well as the fossil fuels employment and related pollutant emissions, indeed, the spread of combined heat and power units and/or renewable sources generators is promoted into both the electrical grids and the thermal networks but are often in conflict with the economic aspects. In this context, the optimal management of complex energy networks - including, in particular, smart district heating - may lead to the achievement of important goals from the environmental and sustainability viewpoints. The aim of this paper is to develop a preliminary methodology for the complete evaluation of complex energy networks, considering energy, economic and environmental aspects. With this purpose, a case study consisting in a network for the fulfillment of electrical and thermal needs of the connected users will be analyzed, considering different scenarios in terms of energy generation mix and operation and applying different optimization software. In addition, the carried out evaluations will allow to set the basis for the discussion about the future of energy policies and possible incentives towards the sustainable development of the energy sector

Pump Hydro Storage and Gas Turbines Technologies Combined to Handle Wind Variability: Optimal Hydro Solution for an Italian Case Study☆

Abstract Load and wind energy profiles are totally uncorrelated, therein lies the problem of variable energy sources. Managing load with increasing wind penetration may call for operational ranges that conventional systems cannot readily access. Storage technologies could allow tolerating the unsteadiness of renewable sources with smaller fossil fuel plants capacity. Pumped Hydro Storage (PHS) is a crucial technology for balancing large steam power plants and may become increasingly important for storing renewable energies. Hence capacity ranges of PHS as well as its dynamic response to renewable power variability, will become progressively relevant. An integrated system made of a wind farm, a PHS plant and a set of gas turbines (GTs), as programmable fossil fuel devices, to handle renewable variability and maximize renewable energy exploitation, is studied in this paper. A specific case study is analyzed: a wind farm with a nameplate capacity equal to that installed in Sardinia is considered. To match the power output requested by the region with the integrated systems different configurations of PHS plant will be investigated. The impact of reversible or separate Francis machines with constant or variable speed will be analyzed in order to minimize electric power output overproduction and GTs fuel consumptions. Minimum and maximum capacity range for reversible or separate machines will be considered. The aim of the study is the optimum sizing and design of a PHS unit in a hybrid wind-hydro-gas turbine power plant to match the load request. Results in terms of PHS operation, water height behavior in upper and lower reservoirs, GT units power output, natural gas consumed and electric power output overproduction will be presented for each analyzed case