Editorial: Emerging Mechanisms in Purinergic Signaling: From Cell Biology to Therapeutic Perspectives

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Emerging roles of purinergic signaling in anti-cancer therapy resistance

Cancer is a complex disease with a rapid growing incidence and often characterized by a poor prognosis. Although impressive advances have been made in cancer treatments, resistance to therapy remains a critical obstacle for the improvement of patients outcome. Current treatment approaches as chemo-, radio-, and immuno-therapy deeply affect the tumor microenvironment (TME), inducing an extensive selective pressure on cancer cells through the activation of the immune system, the induction of cell death and the release of inflammatory and damage-associated molecular patterns (DAMPS), including nucleosides (adenosine) and nucleotides (ATP and ADP). To survive in this hostile environment, resistant cells engage a variety of mitigation pathways related to metabolism, DNA repair, stemness, inflammation and resistance to apoptosis. In this context, purinergic signaling exerts a pivotal role being involved in mitochondrial function, stemness, inflammation and cancer development. The activity of ATP and adenosine released in the TME depend upon the repertoire of purinergic P2 and adenosine receptors engaged, as well as, by the expression of ectonucleotidases (CD39 and CD73) on tumor, immune and stromal cells. Besides its well established role in the pathogenesis of several tumors and in host–tumor interaction, purinergic signaling has been recently shown to be profoundly involved in the development of therapy resistance. In this review we summarize the current advances on the role of purinergic signaling in response and resistance to anti-cancer therapies, also describing the translational applications of combining conventional anticancer interventions with therapies targeting purinergic signaling

Photovoltaics in Net Zero Energy Buildings and Clusters: Enabling the Smart City Operation☆

Abstract From 2012 to comply with the ED 2010/31/EU and its recasts, all new buildings will perform as Nearly Zero Energy Buildings (NearlyZEBs). Buildings are going to be transformed through a careful design into energy generation systems, and the conventional, centralized system of energy generation is going to be replaced by a "web" of energy generation systems. Photovoltaics (PV) seems to be one of the most suitable energy generation technologies for enabling this change, thanks to its "fair" cost, technical features, and multifunctional use in the building's envelope, as well as in the urban environment. PV will be an indispensable technology for Net Zero Energy Buildings (NetZEBs), with the consequence of being a kind of "ubiquitous" technology, also suitable for added uses than the traditional ones. For example: in addition to the multifunctional use in the building's envelope, it might offer advanced services for improving the efficiency and participation in the city processes. A multidisciplinary investigation on possible ways for PV and NetZEBs to change the future urban scenario is proposed, focusing on design, energy management and technological issues to support a Smart City (SC) vision

Ultrasound in the diagnosis of calcium pyrophosphate dihydrate deposition disease. A systematic literature review and a meta-analysis

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New results from an extensive aging test on bakelite Resistive Plate Chambers

We present recent results of an extensive aging test, performed at the CERN Gamma Irradiation Facility on two single--gap RPC prototypes, developed for the LHCb Muon System. With a method based on a model describing the behaviour of an RPC under high particle flux conditions, we have periodically measured the electrode resistance R of the two RPC prototypes over three years: we observe a large spontaneous increase of R with time, from the initial value of about 2 MOhm to more than 250 MOhm. A corresponding degradation of the RPC rate capabilities, from more than 3 kHz/cm2 to less than 0.15 kHz/cm2 is also found.Comment: 6 pages, 7 figures, presented at Siena 2002, 8th Topical Seminar on Innovative Particle and Radiation Detectors 21-24 October 2002, Siena, Ital

A cross-sectional study in Mediterranean European countries to support stakeholders in addressing future market demands: Consumption of farmed fish products

Aquaculture is now a viable alternative to help depleted wild fish stocks and encourage the production of alternative animal protein sources. However, studies have shown that farmed fish has a less positive image in consumers than wild fish. The present study investigates the aspects that most influence the consumption choices of some of the most farmed species in the Mediterranean, sea bass and sea bream. The objective is to analyse the habits and preferences of consumers of these products in Mediterranean countries to identify homogeneous and transversal behaviours in the four countries under analysis in order to recognise common marketing actions and levers. To achieve it, a direct survey was conducted on a representative sample of 6117 consumers from France, Spain, Greece and Italy. The cluster analysis carried out for the four countries revealed 11 well-defined consumer profiles. They showed that different socio-economic characteristics, purchasing habits and product attributes explain a significant part of consumption choices and offer key information for exploring food consumer attitudes. In addition, the role of labelling in consumer behaviour is important to understand which aspects consumers pay more attention to when making their choices, representing a discriminating factor in segmenting respondents' profiles. Understanding these preferences, and the importance of certain information, can be useful to intercept and respond to market demands and to improve consumer confidence in farmed fish products

The Low Energy Tagger for the KLOE-2 experiment

The KLOE experiment at the upgraded DAFNE e+e- collider in Frascati (KLOE-2) is going to start a new data taking at the beginning of 2010 with its detector upgraded with a tagging system for the identification of gamma-gamma interactions. The tagging stations for low-energy e+e- will consist in two calorimeters The calorimeter used to detect low-energy e+e- will be placed between the beam-pipe outer support structure and the inner wall of the KLOE drift chamber. This calorimeter will be made of LYSO crystals readout by Silicon Photomultipliers, to achieve an energy resolution better than 8% at 200 MeV.Comment: 4 pages, 5 figures, in the proceedings of "Frontier detectors for frontier physics", isola d'Elba, Italy, May 200

The P2X7 Receptor 489C>T Gain of Function Polymorphism Favors HHV-6A Infection and Associates With Female Idiopathic Infertility

The P2X7 receptor (P2X7R) is an ATP-gated ion channel known for its proinflammatory activity. Despite its participation in host defense against pathogens, the role played in viral infections, notably those caused by herpes viruses, has been seldom studied. Here we investigated the effect of P2X7R expression on human herpes virus 6 A (HHV-6A) infection of P2X7R-expressing HEK293 cells. We show that functional P2X7R increases while its blockade decreases viral load. Interestingly, HHV-6A infection was enhanced in HEK293 cells transfected with P2X7R cDNA bearing the gain of function 489C>T SNP (rs208294, replacing a histidine for tyrosine at position 155). The P2X7R 489C>T polymorphism correlated with HHV-6A infection also in a cohort of 50 women affected with idiopathic infertility, a condition previously shown to correlate with HHV-6A infection. None of the infertile women infected by HHV-6A was homozygote for 489CC genotype, while on the contrary HHV-6A infection significantly associated with the presence of the rs208294 allele. Levels of soluble human leukocyte antigen G (sHLA-G), a factor promoting embryo implant, measured in uterine flushings negatively correlated with the 489TT genotype and HHV-6A infection, while proinflammatory cytokines interleukins 1α (IL-1α), 1β (IL-1β), and 8 (IL-8) positively correlated with both the 489T allele presence and viral infection. Taken together these data point to the P2X7R as a new therapeutic target to prevent HHV-6A infection and the associated infertility

Probabilistic assessment of Net Transfer Capacity considering forecast uncertainties

In transmission system planning, researchers propose methods to assess the effect of uncertainties of power system operating condition due to forecasting errors of intermittent generation and loads. In particular probabilistic power flow methods are used to calculate the probability distributions of the voltages and the branch currents, starting from the distributions of power injections/absorptions. These uncertainties play a key role in the operational planning of power systems, as certain configurations of load and intermittent generation can cause security problems. This paper aims to propose a probabilistic methodology to assess Net Transfer Capacity (NTC) among network areas, which quantifies forecast error uncertainties by applying the Point Estimate Method (PEM) combined with Third Order Polynomial Normal (TPN) Transformation. This approach is compared with a conventional NTC assessment technique and has been tested on an IEEE test system

P2X7 receptor isoform B is a key drug resistance mediator for neuroblastoma

Drug resistance is a major challenge for all oncological treatments that involve the use of cytotoxic agents. Recent therapeutic alternatives cannot circumvent the ability of cancer cells to adapt or alter the natural selection of resistant cells, so the problem persists. In neuroblastoma, recurrence can occur in up to 50% of high-risk patients. Therefore, the identification of novel therapeutic targets capable of modulating survival or death following classical antitumor interventions is crucial to address this problem. In this study, we investigated the role of the P2X7 receptor in chemoresistance. Here, we elucidated the contributions of P2X7 receptor A and B isoforms to neuroblastoma chemoresistance, demonstrating that the B isoform favors resistance through a combination of mechanisms involving drug efflux via MRP-type transporters, resistance to retinoids, retaining cells in a stem-like phenotype, suppression of autophagy, and EMT induction, while the A isoform has opposite and complementary roles