Eicosanoids and cancer: Focus on melanoma

Inflammation plays a key role in tumor promotion and development. Indeed, high levels of cyclooxygenase-2 (COX-2) expression are associated with worse prognosis in several types of cancer including melanoma. The aim of our project, divided in three sections, has been to investigate on the role of COX-2 in melanoma development and progression. In the first phase of the project, we evaluated the expression of both COX-1 and COX-2 in a large panel of human melanoma cells and assessed the effect of COX-2 ablation on cancer cell proliferation and invasiveness by the mean of siRNA technology and by selective inhibition of COX-2 activity. Translation of in vitro data to in vivo models of cutaneous melanoma showed that in COX-2-/- mice tumor development was almost blunted as compared to littermate control C57Bl/6J. Finally, we performed a retrospective clinical study on 45 human lymph node melanoma metastases and correlated COX-2 expression to progression free survival (PFS). Our results show an inverse correlation between PFS and COX-2 expression suggesting that COX-2 is a negative prognostic factor in metastatic melanoma. In addition to COX enzymes, also hydrogen sulfide (H2S), an endogenous gasotransmitter, has been recently demonstrated to be involved in human melanoma. Thus, the second phase of the project was focused on the evaluation of the efficacy of a new H2S-releasing nonsteroidal anti-inflammatory drugs (H2S-NSAIDs) named ATB-346, developed by combining naproxen with a chemical moiety that donates hydrogen sulfide. In particular, we used cell culture and a murine melanoma model to evaluate the effect of ATB-346 on: i) proliferation of human melanoma cells; ii) melanoma development in mice. Cell culture studies demonstrated that ATB-346 reduced the proliferation of human melanoma cells and this effect was associated to induction of apoptosis and inhibition of NF-κB activation. Moreover in vivo data showed that ATB-346 significantly reduced melanoma development. In conclusion, by using this dual approach we propose that COXs and H2S pathway could be innovative therapeutic targets to generate new treatment options based on “combination therapy” for melanoma. Finally, in the third and last phase of the project, we decided to better define the role of COX-2 in melanoma development. The aim was to establish if this enzyme acts predominantly in the microenvironment rather than in tumor cells. For this purpose we deleted COX-2 in B16/F10 murine melanoma cells by the mean of CRISPR/Cas9 technology. We firstly investigated on the effect of COX-2 knockdown on proliferation, migration, invasion and colonie formation of B16/F10 murine melanoma cells. In vitro studies demonstrated that CRISPR/Cas9-mediated COX-2 knockdown decreased proliferation of B16/F10 cells and inhibited some features of metastatic melanoma such as motility, invasiveness and focus formation. Finally, subcutaneously injection of B16/F10 cells knocked down for COX-2 showed slightly reduced melanoma growth and reduced the CXCL1 chemokine plasma levels. In addition, we also investigated on the expression and role of miR-143-3p in human malignant melanoma that has been shown to be dysregulated in many cancers. Our results showed that the expression of miR-143-3p was lower in human melanoma cells, as well as human tumor biopsy specimens, when compared to normal human melanocytes. Ectopic expression of miR-143-3p in human melanoma cells inhibited proliferation, migration, invasion and promoted apoptosis acting through a molecular mechanism that, at least in part, is dependent on inhibition of the COX-2 gene. Collectively, our findings show that COX-2 has a critical role in modulating melanoma development and progression. Nonetheless, significant challenges still lie ahead for blocking the interactions between the microenvironment and tumors

Exploring Convergence in some OECD Public Social Expenditure Trends

Triggered by the phenomenon of globalisation, during recent years there has been a process of State policy rationalisation in the social expenditure domain; hence the debate over the present role and dimension of welfare state has intensified. Following on the extensive multidisciplinary literature on this issue, the purpose of this paper is two-fold 1) to apply a more traditional analysis of convergence (sigma and beta convergence) in public social expenditures and 2) to analyse public social expenditure allocation expressed as a % of GDP and derive a possible classification of the countries by means of a multivariate approach. We conclude by explaining some similarities in the expenditure behaviour of certain countries in terms of the policy transfer process. Our results can be interpreted as a further contribution to the literature on contemporary public policy evaluation in the welfare domain.Policy Making, Welfare Programme, Public social Expenditures, Policy Transfer, principal component analysis, cluster analysis

Exploring public social expenditure trends in the globalization era

Triggered by the phenomenon of globalisation, during recent years there has been a process of State policy rationalisation in the social expenditure domain; hence the debate over the present role and dimension of welfare state has intensified. Following on the extensive multidisciplinary literature on this issue, the purpose of this paper is two-fold 1) to apply a traditional analysis of convergence (sigma and beta convergence) in public social expenditures and 2) to analyse public social expenditure allocation expressed as a % of GDP and derive a possible classification of the countries by means of a multivariate approach. Our results, revealing that some convergence in the expenditure domain occurred for certain Southern and Northern European countries, can be interpreted as a further contribution to the literature on contemporary public policy evaluation in the welfare domain.peer-reviewe

Exploring public social expenditure trends in the globalization era

Triggered by the phenomenon of globalisation, during recent years there has been a process of State policy rationalisation in the social expenditure domain; hence the debate over the present role and dimension of welfare state has intensified. Following on the extensive multidisciplinary literature on this issue, the purpose of this paper is two-fold 1) to apply a traditional analysis of convergence (sigma and beta convergence) in public social expenditures and 2) to analyse public social expenditure allocation expressed as a % of GDP and derive a possible classification of the countries by means of a multivariate approach. Our results, revealing that some convergence in the expenditure domain occurred for certain Southern and Northern European countries, can be interpreted as a further contribution to the literature on contemporary public policy evaluation in the welfare domain.peer-reviewe

Multilevel evolution shapes the function of NB-LRR encoding genes in plant innate immunity

A sophisticated innate immune system based on diverse pathogen receptor genes (PRGs) evolved in the history of plant life. To reconstruct the direction and magnitude of evolutionary trajectories of a given gene family, it is critical to detect the ancestral signatures. The rearrangement of functional domains made up the diversification found in PRG repertoires. Structural rearrangement of ancient domains mediated the NB-LRR evolutionary path from an initial set of modular proteins. Events such as domain acquisition, sequence modification and temporary or stable associations are prominent among rapidly evolving innate immune receptors. Over time PRGs are continuously shaped by different forces to find their optimal arrangement along the genome. The immune system is controlled by a robust regulatory system that works at different scales. It is important to understand how the PRG interaction network can be adjusted to meet specific needs. The high plasticity of the innate immune system is based on a sophisticated functional architecture and multi-level control. Due to the complexity of interacting with diverse pathogens, multiple defense lines have been organized into interconnected groups. Genomic architecture, gene expression regulation and functional arrangement of PRGs allow the deployment of an appropriate innate immunity response

Una Prima Stima del Residuo Fiscale e del suo Effetto sulla Localizzazione delle Imprese in Cina

In the present work we analyze fiscal differences among Chinese provinces using indexes built on the concept of fiscal residuum. Our analysis help us to verify the role of public transfers in promoting both fiscal equalization and competition among provinces. We further study the impact of the fiscal residua on the localization of foreign enterprises. Our first results show that enterprises are conditioned, in their localization choices, by the general welfare conditions of each jurisdiction. Our results underscore the role of local and central institutions in affecting the productive structures.Public Finance, Fiscal Policy, Revenue, Subsidies, Fiscal residuum

Genome-wide identification and analysis of candidate genes for disease resistance in tomato

Tomato (Solanum lycopersicum L.) has served as an important model system for studying the genetics and molecular basis of resistance mecha- nisms in plants. An unprecedented challenge is now to capitalize on the genetic and genomic achievements obtained in this species. In this study, we show that information on the tomato genome can be used predictively to link resistance function with specific sequences. An integrated genomic approach for identifying new resistance (R) gene candidates was developed. An R gene functional map was created by co-localization of candidate pathogen recognition genes and anchoring molecular markers associated with resistance phenotypes. In-depth characterization of the identified pathogen recognition genes was performed. Finally, in order to highlight expressed pathogen recognition genes and to provide a first step in validation, the tomato transcriptome was explored and basic molecular analyses were conducted. Such methodology can help to better direct positional cloning, reducing the amount of effort required to identify a functional gene. The resulting candidate loci selected are available for exploiting their specific function

Environmental fiscal reform and willingness to pay for the environment: an empirical analysis on European micro data

This paper empirically investigates the determinants of willingness to pay (WTP) for the environment, employing micro data from the European Value Survey (EVS) over 2008-2010 in 27 European countries. Using ordered logit, logit and partially constrained generalized ordered logit models, we explore a wide set of individual and country level determinants. Our particular focus is on whether WTP is influenced by the Environmental Fiscal Reforms (EFR), carried out only in some countries of our sample. Our results show that WTP for the environment is lower in countries where an Environmental Fiscal Reform has been introduced. Moreover, analyses conducted on the role of information highlight that being presumably aware of the environmental fiscal reform does not affect positively the marginal willingness to pay for the environment

Environmental fiscal reform and willingness to pay for the environment: an empirical analysis on European micro data

This paper empirically investigates the determinants of willingness to pay (WTP) for the environment, employing micro data from the European Value Survey (EVS) over 2008-2010 in 27 European countries. Using ordered logit, logit and partially constrained generalized ordered logit models, we explore a wide set of individual and country level determinants. Our particular focus is on whether WTP is influenced by the Environmental Fiscal Reforms (EFR), carried out only in some countries of our sample. Our results show that WTP for the environment is lower in countries where an Environmental Fiscal Reform has been introduced. Moreover, analyses conducted on the role of information highlight that being presumably aware of the environmental fiscal reform does not affect positively the marginal willingness to pay for the environment

Exploring Convergence in some OECD Public Social Expenditure Trends

Triggered by the phenomenon of globalisation, during recent years there has been a process of State policy rationalisation in the social expenditure domain; hence the debate over the present role and dimension of welfare state has intensified. Following on the extensive multidisciplinary literature on this issue, the purpose of this paper is two-fold 1) to apply a more traditional analysis of convergence (sigma and beta convergence) in public social expenditures and 2) to analyse public social expenditure allocation expressed as a % of GDP and derive a possible classification of the countries by means of a multivariate approach. We conclude by explaining some similarities in the expenditure behaviour of certain countries in terms of the policy transfer process. Our results can be interpreted as a further contribution to the literature on contemporary public policy evaluation in the welfare domain