Protein Kinase CK2α′ Is Induced by Serum as a Delayed Early Gene and Cooperates with Ha-ras in Fibroblast Transformation

Protein kinase CK2 is an ubiquitous and pleiotropic Ser/Thr protein kinase composed of two catalytic (alpha and/or alpha') and two noncatalytic (beta) subunits forming a heterotetrameric holoenzyme involved in cell growth and differentiation. Here we report the identification, cloning, and oncogenic activity of the murine CK2alpha' subunit. Serum treatment of quiescent mouse fibroblasts induces CK2alpha' mRNA expression, which peaks at 4 h. The kinetics of CK2alpha' expression correlate with increased kinase activity toward a specific CK2 holoenzyme peptide substrate. The ectopic expression of CK2alpha' (or CK2alpha) cooperates with Ha-ras in foci formation of rat primary embryo fibroblasts. Moreover, we observed that BALB/c 3T3 fibroblasts transformed with Ha-ras and CK2alpha' show a faster growth rate than cells transformed with Ha-ras alone. In these cells the higher growth rate correlates with an increase in calmodulin phosphorylation, a protein substrate specifically affected by isolated CK2 catalytic subunits but not by CK2 holoenzyme, suggesting that unbalanced expression of a CK2 catalytic subunit synergizes with Ha-ras in cell transformation

Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose

N.R.J. was supported by a Diabetes UK RW and JM Collins Studentship (12/0004601). J.B. was supported by a European Foundation for the Study of Diabetes (EFSD) Albert Renold Young Scientist Fellowship and a Studienstiftung des deutschen Volkes PhD Studentship. D.T. was supported by an Advanced Grant from the European Research Commission (268795). G.A.R. was supported by Wellcome Trust Senior Investigator (WT098424AIA) and Royal Society Wolfson Research Merit Awards, and by MRC Programme (MR/J0003042/1), Biological and Biotechnology Research Council (BB/J015873/1), and Diabetes UK Project (11/0004210) grants. G.A.R. and M.W. acknowledge COST Action TD1304 Zinc-Net. D.J.H. was supported by Diabetes UK R.D. Lawrence (12/0004431), EFSD/Novo Nordisk Rising Star and Birmingham Fellowships, a Wellcome Trust Institutional Support Award, and an MRC Project Grant (MR/N00275X/1) with G.A.R. D.J.H and G.A.R. were supported by Imperial Confidence in Concept (ICiC) Grants. J.F. was supported by an MRC Programme grant (MR/L02036X/1). L.P. provided human islets through collaboration with the Diabetes Research Institute, IRCCS San Raffaele Scientific Institute (Milan), within the European islet distribution program for basic research supported by JDRF (1-RSC-2014-90-I-X). P.M. and M.B. were supported by the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 155005 (IMIDIA), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution, and by the Italian Ministry of University and Research (PRIN 2010-2012). D.B. and E.B. provided human islets through the European Consortium for Islet Transplantation sponsored by JDRF (1-RSC-2014-100-I-X)

ADCY5 couples glucose to insulin secretion in human islets

Single nucleotide polymorphisms (SNPs) within the ADCY5 gene, encoding adenylate cyclase 5, are associated with elevated fasting glucose and increased type 2 diabetes (T2D) risk. Despite this, the mechanisms underlying the effects of these polymorphic variants at the level of pancreatic β-cells remain unclear. Here, we show firstly that ADCY5 mRNA expression in islets is lowered by the possession of risk alleles at rs11708067. Next, we demonstrate that ADCY5 is indispensable for coupling glucose, but not GLP-1, to insulin secretion in human islets. Assessed by in situ imaging of recombinant probes, ADCY5 silencing impaired glucose-induced cAMP increases and blocked glucose metabolism toward ATP at concentrations of the sugar >8 mmol/L. However, calcium transient generation and functional connectivity between individual human β-cells were sharply inhibited at all glucose concentrations tested, implying additional, metabolism-independent roles for ADCY5. In contrast, calcium rises were unaffected in ADCY5-depleted islets exposed to GLP-1. Alterations in β-cell ADCY5 expression and impaired glucose signaling thus provide a likely route through which ADCY5 gene polymorphisms influence fasting glucose levels and T2D risk, while exerting more minor effects on incretin action

Going Deeper into the S of ESG: A Relational Approach to the Definition of Social Responsibility

ESG frameworks have progressively become central in economic and policy choices. This is why it is of utmost importance to build a shared and accepted framework to define what we really mean by ESG overcoming the “minimalist” Do Not Significantly Harm (DNSH) principle and moving toward the full achievement of the more ambitious substantial contribution (SC) principle, oriented to the maximization of the social and environmental impact of value creation. To move forward in this direction, our work proposes a relational approach for the assessment of ESG factors focusing in particular on the social pillar. Our conceptual and theoretical proposal argues that, in order to increase the value of that pillar, it is necessary to assess both the internal and external relationships of the firm from an impact perspective, improving at the same time the multidimensional well-being of workers and the capacity to create sustainable development in the local community. The main factors companies should consider to achieve these goals are related to the domains of sense of community, empowerment, good practices of mutual aid and degree of participation at individual, team, organization, and territorial levels that can trigger gift giving, reciprocity and trust, overcoming standard social dilemmas and producing superadditive outcomes together with high social and environmental impact. Starting from these elements, this work proposes a set of indicators and metrics, based on an original methodology to measure and assess the commitment of a firm to increasing social factors. This methodology is particularly suitable for SMEs and start-up companies

The frontier of social impact finance in the public sector: Theory and two case studies

Social impact bonds (SIBs) are a novel and innovative form of public-private partnership financing social services performed by a best-practice selected non-governmental third entity. In our paper we outline a SIB theoretical model identifying government and private investors' participation constraints and we discuss the conflicts of interests that may arise among the different actors involved in presence of asymmetric information. We apply our theoretical model to two investment cases concerning contrast to jail recidivism and health budget project. We show conditions for viability of the SIB scheme in both cases under reasonable parametric conditions, provide sensitivity analysis on crucial parameters, and calculate participants' payoffs under different assumptions

Going Deeper into the S of ESG: A Relational Approach to the Definition of Social Responsibility

ESG frameworks have progressively become central in economic and policy choices. This is why it is of utmost importance to build a shared and accepted framework to define what we really mean by ESG overcoming the “minimalist” Do Not Significantly Harm (DNSH) principle and moving toward the full achievement of the more ambitious substantial contribution (SC) principle, oriented to the maximization of the social and environmental impact of value creation. To move forward in this direction, our work proposes a relational approach for the assessment of ESG factors focusing in particular on the social pillar. Our conceptual and theoretical proposal argues that, in order to increase the value of that pillar, it is necessary to assess both the internal and external relationships of the firm from an impact perspective, improving at the same time the multidimensional well-being of workers and the capacity to create sustainable development in the local community. The main factors companies should consider to achieve these goals are related to the domains of sense of community, empowerment, good practices of mutual aid and degree of participation at individual, team, organization, and territorial levels that can trigger gift giving, reciprocity and trust, overcoming standard social dilemmas and producing superadditive outcomes together with high social and environmental impact. Starting from these elements, this work proposes a set of indicators and metrics, based on an original methodology to measure and assess the commitment of a firm to increasing social factors. This methodology is particularly suitable for SMEs and start-up companies

Modelos financieros para el desarrollo sostenible de la Administración Pública

Las Administraciones Públicas están cada vez más llamadas a convertirse en protagonistas de la transición hacia el desarrollo sostenible. En esta perspectiva, es necesario pensar en modelos financieros capaces de catalizar recursos públicos y orientarse intencionalmente hacia la implementación de políticas y proyectos funcionales a la transición. Para implementar las políticas públicas de sostenibilidad de manera óptima, no basta la simple referencia a los Objetivos de Desarrollo Sostenible (ODS), que también son una referencia útil y reconocida. Es importante definir estrategias que también definan los métodos de asociación públicoprivada y los de financiamiento de los proyectos de impacto ambiental y social seleccionados. Con esto en mente, el artículo propone un mapeo de las experiencias de finanzas sostenibles en España y en los países de América Latina, clasificándolas según los ODS y las estructuras financieras adoptadas

Un Modello di Impact Finance per i Comuni: il Piano Strategico di Mandato BES-Oriented

Il presente lavoro propone un modello di Impact Finance per i Comuni italiani, utile a coniugare le politiche di bilancio delle amministrazioni locali con gli obiettivi sociali ed ambientali riconducibili agli indicatori di Benessere Equo e Sostenibile. Nello specifico, il Piano Strategico di Mandato BES-Oriented prevede: (i) un’analisi di contesto utile a definire il posizionamento BES del Comune, (ii) un’analisi di bi- lancio pubblico BES-Oriented, utile a definire l’impatto diretto delle politiche di bilancio sui temi sociali ed ambientali (iii) una matrice che consente una lettura com- binata del posizionamento e del bilancio, (iv) l’utilizzo delle interazioni fra domini BES per valutare gli impatti indiretti delle politiche di bilancio sugli aspetti sociali ed ambientali. Il modello proposto consente alle Amministrazioni locali di definire priorità strategiche ed obiettivi di impatto ed in particolare di: adottare delle strategie di welfare in relazione ad un benchmark; collegare l’attivazione di specifiche progettualità in maniera sinergica, riferendole ad una o più voci di spesa pubblica ed al relativo dominio BES che ad esse viene associato; valutare l’impatto diretto che la pianificazione comunale ed i singoli progetti hanno sui conti pubblici; individuare ulteriori dimensioni di benessere sulle quali un investimento impatterà indiretta- mente, offrendo un quadro complessivo dell’impatto in termini di miglioramento delle condizioni di vita dei cittadini; calcolare gli impatti diretti ed indiretti sulla spesa pubblica (effetto moltiplicatore)

Multi-Stakeholder Impact Environmental Indexes: The Case of NeXt

The design of proper environmental and social indicators is one of the most critical challenges when monitoring and implementing corporate and government policy measures toward ecological transitions and sustainable development. In our paper we outline and discuss the characteristics of a new vintage of “living” multi-stakeholder community-based indicators based on the principles of self-evaluation, dialogue and simplification with a specific focus on the NeXt index. We explain the main differences between them and the opposite extreme of static expert-based indicators, how they integrate firm-level scores with compliance with macro multidimensional wellbeing indicators (such as the UN Sustainable Development Goals) and how they complement with ongoing regulatory standards currently under development. As well, we discuss caveats, policy implications and impact in terms of subjective wellbeing