Regulation of Cardiomyocyte Proliferation by microRNAs and Small Molecules

Understanding the molecular mechanisms regulating cardiac cell proliferation during the embryonic, fetal and adult life holds a paramount importance in view of developing innovative strategies aimed at inducing myocardial regeneration after cardiac damage. Previous high throughput screening studies in our laboratory identified a series of microRNAs able to trigger cardiomyocyte proliferation and stimulate cardiac regeneration after myocardial infarction. In the first part of this project, we investigated the mechanism of action of the top ten most effective of these miRNAs, revealing an involvement of the Hippo-YAP pathway in their action. We found that all the investigated miRNAs activated YAP-mediated transcription, nuclear localization of active YAP and increased expression of YAP responsive genes. Of notice, miR-199a-3p, one of the most effective miRNAs exerted its direct effect on two mRNA targets impinging on the Hippo pathway, the inhibitory kinase TAOK1 and the E3 ubiquitin ligase, β−TrCP. Most of the miRNAs inducing proliferation (including miR-199a-3p) also modulated the dynamics of the actin cytoskeleton in the treated cardiomyocytes, which displayed a rounded shape and gross bundles of actin fibers at the cytoplasm periphery. Consistent with these observations, we found that the Cofilin2 mRNA was a direct target of four of the investigated miRNAs and that downregulation of Cofilin2 itself was sufficient to promote cardiomyocyte proliferation, activate nuclear translocation of YAP and stimulate transcription of TEAD-responsive genes. The second part of the project was aimed at identifying small molecules exerting a mitogenic effect on neonatal cardiomyocytes through an unbiased high-throughput screening (HTS) of a library of 780 FDA-registered drugs. The neuroactive alkaloid harmine was identified as the most powerful molecule at inducing cardiomyocyte proliferation in vitro and heart regeneration after myocardial infarction in vivo. Harmine exerted its activity through the inhibition of the dual specificity phosphorylation-regulated tyrosine kinase, Dyrk1a and, again, the activation of YAP nuclear translocation. Collectively, these results identify both YAP activation and actin cytoskeleton remodelling as major determinants of cardiomyocyte proliferation and establish the molecular basis for the development of pharmacological therapies to promote heart regeneration through the stimulation of the endogenous capacity of cardiomyocytes to proliferate

Edna Manley\u27s The Diaries : Cultural Politics and the Discourse of Self

A critic of imperialism, race and class privilege, sculptor Edna Manley contributed to the ascendancy of a West Indian cultural aesthetic. Her productivity in the creative arts and her promotion of indigenous cultural organizations were vital to the growth of a post-colonial identity expressing Jamaican national unity and cultural plurality. The wife of Premier Norman W. Manley and the mother of Michael Manley, Jamaica\u27s former Prime Minister, she drew strength from her cross-cultural heritage as a British-trained artist seeking to express the collective unconsciousness of her people. Her creative work finds its symbols in the subaltern currents of Caribbean life in the ongoing processes of community-making that forge a national identity out of peoples displaced from many lands. Her art is integrative: Afro-Caribbean and European themes merge in a symbolic universe suggesting wholeness. Her self-reflections, in diary form, also illustrate her determination to link opposing metaphors of the self into a central, organizing image

Participatory Modeling for Sustainable Development in Water and Agrarian Systems: Potential and Limits of Stakeholder Involvement

Resource /Energy Economics and Policy,

How can I learn more when I collaborate in a virtual group?

Learning in virtual groups has been a process studied and analysed long from multiple perspectives. However, the literature is scarce when we look for models to explain information problem solving skills in online collaboration. A descriptive model of cognitive skills involved in individual information problem solving while using internet information can be found in recent research. The purpose of this study was to find out what information problem solving skills (IPS) students apply when working collaboratively online, and secondly, to analyse what differentiates students who do well on their knowledge tests after collaboration, in relation to these IPS skills. We conducted a research with more than 40 students in 10 virtual groups to analyse the correlation between learning and IPS skills applied by students during an online task that lasted more than 4 weeks. Students completed a weekly self-report with actions related to IPS skills and time devoted to the collaborative task. Findings show that students applied more frequently the skill to check the communication (30%), secondly, read de information (22%), in the third place exchange information (20%), followed by write the information (15%), analyze the information (8%), and finally, search for information (5%). However, only three skills correlate with learning: information exchange, analysis of information and checking communication. Two of them (exchange and check) are collaborative skills and one of them (analysis) is an information problem-solving skill. The conclusions of this study may provide guidelines for instructors and students on ways to improve learning in online collaborative group work

Barriers to innovation and subsidy effectiveness

We explore the effects of subsidies by means of a model of firms' decisions about performing R&D when some government support can be expected. We estimate it with data on about 2,000 performinga nd nonperformingS panishm anufacturingfi rms. Wec omputet he subsidies required to induce R&D spending, we detect the firms that would cease to perform R&D without subsidies, and assess the change in the privately financed effort. Results suggest that subsidies stimulate R&D and some firms would stop performing in their absence, but most actual subsidies go to firms that would have performed R&D otherwise. We find no crowding out of private funds.Publicad

Corporate Environmental Disclosure Practices in Different National Contexts: The Influence of Cultural Dimensions

The influence of different national contexts, including the effects of cultural environments, on corporate environmental disclosure practices has yet to be properly addressed in the literature. The purpose of this research is, therefore, to analyse how cultural factors affect the environmental disclosure practices of companies in different countries. This research is supported by the diversity of cultures across countries. Given that a cultural framework prompts different organisational actions and strategies, the question to be answered through this research is as follows: How do cultural aspects affect corporate environmental disclosure? Cultural factors are precisely those that can explain similarities and differences between stakeholders’ actions and preferences. The sample used in this research comprises companies in 28 countries and 9 economic sectors for the period 2004 to 2015. Our main findings show that companies operating in countries with individualist, masculine and indulgent cultures are less likely to disclose environmental information. Contrary to our predictions, cultures with a longterm orientation also discourage the reporting of environmental information, while uncertainty avoidance contexts tend to promote more environmental reporting

Satellite imagery fusion with an equalized trade-off between spectral and spatial quality

En este trabajo se propone una estrategia para obtener imágenes fusionadas con calidad espacial y espectral equilibradas. Esta estrategia está basada en una representación conjunta MultiDirección-MultiRresolución (MDMR), definida a partir de un banco de filtros direccional de paso bajo, complementada con una metodología de búsqueda orientada de los valores de los parámetros de diseño de este banco de filtros. La metodología de búsqueda es de carácter estocástico y optimiza una función objetivo asociada a la medida de la calidad espacial y espectral de la imagen fusionada. Los resultados obtenidos, muestran que un número pequeño de iteraciones del algoritmo de búsqueda propuesto, proporciona valores de los parámetros del banco de filtro que permiten obtener imágenes fusionadas con una calidad espectral superior a la de otros métodos investigados, manteniendo su calidad espacial

AN ECONOMIC MODELLING APPROACH FOR VULNERABILITY ASSESMENT IN IRRIGATION FARMS IN SPAIN

Farm Management,

THE MEASUREMENT OF COMPLIANCE WITH INTERNATIONAL ISA700: THE CASE OF AUDIT REPORTS PUBLISHED BY THE BIG ACCOUNTING FIRMS IN TUNISIA

This article examines the form and content of auditor¿s report published by Tunisian auditors who represent international auditing firms. It measures the compliance of these reports with elements enumerated by International standard on auditing (ISA700). To reach this objective, an empirical study has been conducted based on an analysis of 42 audit reports published in the Tunisian context. The results show that in Tunisia audit reports issued by the international auditing firms are not equally compliant with five of the twenty-six elements enumerated by International Federation of Accountants (IFAC). This difference of conformity to ISA700 can be explained by characteristics of the Tunisian environment (inefficient stock market and a weak number of large holding corporations, among others), which may induce auditors to disregard some elements followed by the same ISA.compliance, form of auditor’s report, content of auditor’s report, auditing in Tunisia