A collaborative approach to forecasting product–service systems (PSS)

Copyright @ Springer-Verlag London Limited 2010. The final version of this article may be viewed at the link below.This paper examines the forecasting implications for product–service systems (PSS) applications in manufacturing firms. The approach taken is to identify the scope of operations for PSS applications by identifying all the activities associated with the service deployment in the telecom sector. The paper then develops a revenue model for manufacturing firms providing PSS applications. The revenue model identifies three generic revenue streams that provide the basis for discussion on the differences in forecasting approaches, including collaborative approaches based on PSS staff being geographically co-located

LEM-3 – A LEM Domain Containing Nuclease Involved in the DNA Damage Response in C. elegans

The small nematode Caenorhabditis elegans displays a spectrum of DNA damage responses similar to humans. In order to identify new DNA damage response genes, we isolated in a forward genetic screen 14 new mutations conferring hypersensitivity to ionizing radiation. We present here our characterization of lem-3, one of the genes identified in this screen. LEM-3 contains a LEM domain and a GIY nuclease domain. We confirm that LEM-3 has DNase activity in vitro. lem-3(lf) mutants are hypersensitive to various types of DNA damage, including ionizing radiation, UV-C light and crosslinking agents. Embryos from irradiated lem-3 hermaphrodites displayed severe defects during cell division, including chromosome mis-segregation and anaphase bridges. The mitotic defects observed in irradiated lem-3 mutant embryos are similar to those found in baf-1 (barrier-to-autointegration factor) mutants. The baf-1 gene codes for an essential and highly conserved protein known to interact with the other two C. elegans LEM domain proteins, LEM-2 and EMR-1. We show that baf-1, lem-2, and emr-1 mutants are also hypersensitive to DNA damage and that loss of lem-3 sensitizes baf-1 mutants even in the absence of DNA damage. Our data suggest that BAF-1, together with the LEM domain proteins, plays an important role following DNA damage – possibly by promoting the reorganization of damaged chromatin

Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?

[EN] Academic spin-offs (ASOs) help universities transfer knowledge or technology through business projects developed by academic staff. This investigation aims at analyzing the critical factors for spin-off creation at universities operating in crisis-raven, entrepreneurship-unfriendly environments. Such factors revolve around four types of resources: environmental, institutional, organizational, and personal. Focusing on a Southern European context, as an example of an unfriendly environment affected by economic crisis, an entrepreneurial university (the Technical University of Valencia in Spain, UPV) is our research setting. Through a case study approach, we examine the potential of UPV as a springboard for ASOs. Our results show an adverse local environment, a rather favorable influence of institutional and organizational drivers, and a mixed role of personal factors. Our findings illustrate that UPV consistently supports spin-off creation due to a greater (rather positive) reflexivity from its institutional, organizational and personal resources than the (negative) imprinting of the unfriendly environment. This helps counter-balance the structural unfriendliness for academic entrepreneurship, and trigger a crisis-led risk-taking attitude by academic staff. Hence, UPV should continue with its current strategy of supporting academic entrepreneurship, and might transfer best practices to other universities also affected by unfavorable environmental conditions. Generally speaking, we would advise universities facing adverse circumstances to develop rules and mechanisms for academic entrepreneurship, carefully revise and improve malfunctions, and become involved throughout the whole process of spin-off development. All in all, our study advances understanding of how the different drivers for ASO creation can be revamped by universities located in unfriendly environments, having in mind the key role that universities play in fostering social and economic development through academic entrepreneurship in such environments.The authors would like to thank the Universitat Politecnica de Valencia (grant PAID-06-12-0916), and the Spanish Ministry of Economy and Competitiveness (grant ECO2011-29863), for their financial support for this research.Seguí-Mas, E.; Oltra, V.; Tormo-Carbó, G.; Sarrión Viñes, F. (2017). Rowing against the wind: how do times of austerity shape academic entrepreneurship in unfriendly environments?. International Entrepreneurship and Management Journal. 1-42. doi:10.1007/s11365-017-0478-zS142Acs, Z. J., Audretsch, D. B., & Lehmann, E. E. (2013). The knowledge spillover theory of entrepreneurship. Small Business Economics, 41, 757–774.Alemany, L. (2011). Libro blanco de la iniciativa emprendedora en España. Resource document. ISEAD. http://idl.isead.edu.es:8080/jspui/bitstream/123456789/859/1/658ALElib.pdf . Accessed 31 October 2015.Algieri, B., Aquino, A., & Succurro, M. (2013). Technology transfer offices and academic spin-off creation: the case of Italy. Journal of Technology Transfer, 38(4), 382–400.ARWU (2017). Academic Ranking of World Universities 2017. Resource document. http://www.shanghairanking.com/ARWU2017.html . Accesed 15 August 2017.Ashcroft, B., Holden, D., & Low, K. (2004). Potential entrepreneurs and the self employment choice decision. In Strathclyde Discussion papers in Economics, 4–16. Glasglow: University of Strathclyde.Autio, E., & Kauranen, I. (1994). Technologist-entrepreneurs versus nonentrepreneurial technologists: Analysis of motivational triggering factors. Entrepreneurship & Regional Development, 6, 315–328.Autio, E., Kenney, M., Mustar, P., Siegel, D., & Wright, M. (2014). Entrepreneurial innovation: The importance of context. Research Policy, 43, 1097–1108.Bonnacorsi, A., Colombo, M. G., Guerini, M., & Rossi-Lamastra, C. (2013). University specialization and new firm creation across industries. Small Business Economics, 41, 837–863.Bruneel, J., Van de Velde, E., & Clarysse, B. (2013). Impact of the type of corporate spin-off on growth. Entrepreneurship Theory and Practice, 37, 943–959.CampusHabitat5U (2017). International Campus of Excellence. Resource document. UPV. http://campushabitat5u.es/?lang=en . Accessed 5 October 2017.Chiesa, V., & Piccaluga, A. (2000). Exploitation and diffusion of public research: The chase of academic spin-offs companies in Italy. R&D Management, 30, 329–339.Clark, B. R. (1998). Creating entrepreneurial universities: Organizational pathways of transformation. New York: IAU Press.Clarysse, B., & Moray, N. (2004). A process study of entrepreneurial team formation: The case of research-based spin-off. Journal of Business Venturing, 19, 55–79.Cohen, M., Nelson, R., & Walsh, J. (2002). Links and impacts: The influence of public research on industrial R&D. Management Science, 48, 1–23.Creswell, J.W. & Clark, V. (2011). Designing and Conducting Mixed Methods Research. SAGE Publications.De Cleyn, S. H., Braet, J., & Klofsten, M. (2015). How human capital interacts with the early development of academic spin-offs. International Entrepreneurship and Management Journal, 11(3), 599–621.Doutriaux, J., & Peterman, D. (1982). Technology transfer and academic entrepreneurship. Babson Park: Frontiers of Entrepreneurship Research, Babson College Entrepreneurship Research Conference (BCERC).Eisenhardt, K. M. (1989). Building Theories from Case Study Research. Academy of Management Review, 14(4), 532–550.European Commission (2017). Erasmus 2013–14. Top 500 higher education institutions receiving Erasmus students. Resource document. EC. http://ec.europa.eu/dgs/education_culture/repository/education/library/statistics/2014/erasmus-receiving-institutions_en.pdf Accessed 5 October 2017.Eurovoc (2017). Mutilingual Thesaurus of the European Union. Resource document. http://eurovoc.europa.eu Accessed 03 February 2017.Franzoni, C. & Lissoni, F. (2006). Academic entrepreneurship, patents and spinoffs: Critical issues and lessons for Europe. CESPRI, Università Commerciale “Luigi Bocconi”. Working Paper No. 80.Fritsch, M., & Aamoucke, R. (2013). Regional public research, higher education, and innovative start-ups: An empirical investigation. Small Business Economics, 41, 865–885.Gartner, W. B. (1985). A conceptual framework for describing the phenomenon of new venture creation. The Academy of Management Review, 10, 696–706.Gartner, W. B. (1988). Who is an entrepreneur? is the wrong question. American Journal of Small Business, 12, 11–32.Geuna, A., & Nesta, L. J. J. (2006). University Patenting and its Effects on Academic Research: The merging European Evidence. Research Policy, 35, 790–807.Gibbert, M., & Ruigrok, W. (2010). The “What” and “How” of the case Study Rigor: Three Strategies based on Published Work. Organizational Research Methods, 13(4), 710–737.Gómez Gras, J. M., Galiana Lapera, D. R., Mira Solves, I., Verdú Jover, A. J., & Sancho Azuar, J. (2008). An empirical approach to the organisational determinants of spin-off creation in European universities. International Entrepreneurship and Management Journal, 4(2), 187–198.Grandi, A., & Grimaldi, R. (2005). Academics' organizational characteristics and the generation of successful business ideas. Journal of Business Venturing, 20(6), 821–845.Güemes, J.J. (2011), “Global Entrepreneurship Monitor. Informe GEM España 2010”. Resource document. GEM España. http://www.gemconsortium.org/docs/download/616. Accessed 15 January 2015 .Guerrero, M., & Urbano, D. (2012). The development of an entrepreneurial university. Journal of Technology Transfer, 37(1), 43–74.Guerrero, M., Urbano, D., Cunningham, J., & Organ, D. (2014). Entrepreneurial universities in two European regions: a case study comparison. Journal of Technology Transfer, 39(3), 415–434.Hoang, H., & Antoncic, B. (2003). Network-based research in entrepreneurship: A critical review. Journal of Business Venturing, 18(2), 165–187.Hofstede, G. (1980). Culture’s Consequences. International differences in work-related values. Beverly Hills: Sage.Hofstede, G. (2001). Culture’s consequences: Comparing values, behaviours, institutions, and organizations across nations (2nd ed.). Thousand Oaks: Sage.Hülsbeck, M., & Pickavé, E. N. (2014). Regional knowledge production as determinant of high-technology entrepreneurship: Empirical evidence for Germany. International Entrepreneurship and Management Journal, 10, 121–138.INE (2016). INEbase: Operaciones estadísticas. Instituto Nacional de Estadística (National [Spanish] Statistical Institute). Resource document. INE. http://www.ine.es/inebmenu/indice.htm . Accessed 2 July 2016.Kalar, B., & Antoncic, B. (2015). The entrepreneurial university, academic activities and technology and knowledge transfer in four European countries. Technovation, 36-37, 1–11.Kroll, H. (2009). Demonstrating the instrumentality of motivation oriented approaches for the explanation of academic spin-off formation—an application based on the Chinese case. International Entrepreneurship and Management Journal, 5, 97–116.LAEI (2013). Ley 14/2013, de 27 de septiembre, de Apoyo a Emprendedores y su Internacionalización (‘Act of Support to Entrepreneurs and their Internationalization’). Government of Spain, 27 September. Resource document: http://www.boe.es/boe/dias/2013/09/28/pdfs/BOE-A-2013-10074.pdf . Accessed 10 March 2016.Lam, A., & De Campos, A. (2015). Content to be sad’ or ‘runaway apprentice’? The psychological contract and career agency of young scientists in the entrepreneurial university. Human Relations, 68(5), 811–841.LCTI (2011). Ley 14/2011, de 1 de junio, de la Ciencia, la Tecnología y la Innovación (‘Science, Technology and Innovation Act’). Government of Spain, 1 June. Resource document: http://www.boe.es/boe/dias/2011/06/02/pdfs/BOE-A-2011-9617.pdf . Accessed 10 March 2016.León-Darder, F. (2016). La internacionalització de l’empresa valenciana. In E. Seguí-Mas (Ed.), Una nova via per a l’empresa valenciana (pp. 61–80). Catarroja: Editorial Afers & Fundació Nexe.LES (2011). Ley 2/2011, de 4 de marzo, de Economía Sostenible (‘Sustainable Economy Act’). Government of Spain, 4 March, Resource document. http://www.boe.es/boe/dias/2011/03/05/pdfs/BOE-A-2011-4117.pdf. Accessed 10 March 2016 .Leyden, D. P., & Link, A. N. (2013). Knowledge spillovers, collective entrepreneurship, and economic growth: The role of universities. Small Business Economics, 41, 797–817.Lindelöf, P., & Löfsten, H. (2006). Environmental hostility and firm behavior – An empirical examination of new technology-based firms on science parks. Journal of Small Business Management, 44(3), 386–406.Link, N., & Scott, T. (2005). Opening the ivory’s tower door: An analysis of the determinants of the formation of US university spin-off companies. Research Policy, 34, 1106–1112.Lockett, A., & Wright, M. (2005). Resources, capabilities, risk capital and the creation of university spin-out companies. Research Policy, 34, 1043–1057.LOMLOU (2007). Ley Orgánica 4/2007, de 12 de abril, por la que se modifica la Ley Orgánica 6/2011, de 21 de diciembre, de Universidades (‘Act of Modification of the University Act’). Government of Spain, 12 April. Resource document. https://www.boe.es/boe/dias/2007/04/13/pdfs/A16241-16260.pdf (accessed 11 March 2016).LOU (2001). Ley Orgánica 6/2001, de Universidades (‘University Act’). Government of Spain, 21 December. Resource document: https://www.boe.es/boe/dias/2001/12/24/pdfs/A49400-49425.pdf . Accessed 11 March 2016.Martinelli, A., Meyer, M., & Von Tunzelmann, N. (2008). Becoming an entrepreneurial university? A case study of knowledge exchange relationships and faculty attitudes in a medium-sized, research-oriented university. Journal of Technology Transfer, 33, 259–283.Martínez Carrascal, C. & Mulino Ríos, M. (2014). La evolución del crédito bancario a las empresas españolas según su tamaño. Un análisis basado en la explotación conjunta de la información de la CIR y de la CBI, Boletín Económico - Banco de España, Enero (January), pp. 117–125.Mathias, B. D., Williams, D. W., & Smith, A. R. (2015). Entrepreneurial inception: The role of imprinting in entrepreneurial action. Journal of Business Venturing, 30(1), 11–28.MIET (Spanish Ministry of Industry, Energy and Tourism) (2012). Estadísticas Pyme. Evolución e indicadores. No. 10″, Resource document. http://www.ipyme.org/Publicaciones/ESTADISTICAS_PYME_N10_2011.pdf. Accessed 2 May 2016 .Miles, M.B. & Huberman, A.M. (2008). Qualitative Data Analysis: an expanded sourcebook. Sage Publications.Morales-Gualdrón, S. Y., Gutiérrez-Gracias, & Roig Dobón, S. (2009). The entrepreneurial motivation in academia: A multidimensional construct. International Entrepreneurship and Management Journal, 6, 301–317.Mosey, S., & Wright, M. (2007). From human capital to social capital: A longitudinal study of technology-based academic entrepreneurs. Entrepreneur, 31, 909–936.Mosey, S., Lockett, A., & Westhead, P. (2006). Creating network bridges for university technology transfer: The Medici fellowship programme. Technology Analysis and Strategic Management, 18, 71–91.Mosey, S., Wright, M., & Clarysse, B. (2012a). Transforming traditional university structures for the knowledge economy through multidisciplinary institutes. Cambridge Journal of Economics, 36, 587–607.Mosey, S., Noke, H., & Binks, M. (2012b). The influence of human and social capital upon the entrepreneurial intentions and destinations of academics. Technology Analysis and Strategic Management, 24, 893–910.Moutinho, R., Au-Yong-Oliveira, M., Coelho, A., & Manso, J. P. (2016). Determinants of knowledge-based entrepreneurship: an exploratory approach. International Entrepreneurship and Management Journal, 12(1), 171–197.Mowery, D. C., Nelson, R. R., Sampat, B. N., & Ziedonis, A. A. (2001a). The growth of patenting and licensing by US universities: an assessment of the effects of Bayle-Dole Act of 1980. Research Policy, 30(1), 99–119.Mowery, D. C., Sampat, B. N., & Ziedonis, A. A. (2001b). Learning to patent: institutional experience, learning, and the characyeristics of US university Patents after the Bayle-Dole Act, 1981-1992. Management Science, 48(1), 73–89.O’Shea, R., Allen, J., Chevalier, A., & Roche, F. (2005). Entrepreneurial orientation, technology transfer and spinoff performance of US universities. Research Policy, 34, 994–1009.O’Shea, R., Allen, T., Morse, K., O’Gorman, C., & Roche, F. (2007). Delineating the anatomy of an entrepreneurial university: the Massachusetts Institute of Technology Experience. R&D Management, 37(1), 1–16.O’Shea, R., Chugh, H., & Allen, T. (2008). Determinants and consequences of university spinoff activity: A conceptual framework. Journal of Technology Transfer, 33, 653–666.Ortín, P., Salas, V., Trujillo, M.V., & Vendrell, F. (2007). El spin-off universitario en España como modelo de creación de empresas intensivas en tecnología. Ministerio de Industria, Turismo y Comercio. Secretaría General de Industria. Dirección General de Política de la Pyme. Resource document. http://www.ipyme.org/Publicaciones/Informe spinnoff.pdf . Accessed 2 October 2016.Papaoikonomou, E., Segarra, P., & Li, X. (2012). Entrepreneurship in the context of crisis: Identifying barriers and proposing strategies. International Advances in Economic Research, 18, 111–119.Piperopoulos, P., & Piperopoulos, G. (2010). Is Greece finally on the right path toward entrepreneurship, innovation, and business clusters? International Journal of Public Administration, 33(1), 55–59.Powers, B., & McDougall, P. (2005). University startup formation and technology licensing with firms that go public: A resource-based view of academic entrepreneurship. Journal of Business Venturing, 20, 291–311.Red OTRI (2016). Informe de la Encuesta de Investigación y Transferencia 2014 de las universidades españolas. Resource document. http://www.redotriuniversidades.net/index.php/informa-encuesta/6-encuesta-redotri/informa-encuesta-2014/download . Accessed 22 June 2016.Redero San-Román, M. (2002). Origen y desarrollo de la universidad franquista. Studia Zamorensia, 6, 337–352.Rodríguez-Gulías, M. J., Rodeiro-Pazos, D., & Fernández-López, S. (2017). The effect of university and regional knowledge spillovers on firms’ performance: an analysis of the Spanish USOs. International Entrepreneurship and Management Journal, 13(1), 191–209.Rodríguez-San Pedro, L.E. (2014). Las universidades españolas en su contexto historic. Resource document. Universia. http://universidades.universia.es/universidades-de-pais/historia-de-universidades/historia-universidad-espanola/pasado-reciente/pasado-reciente-multiplicidad-regimen-autonomico.html . Accessed 28 July 2015.Samsom, K., & Gurdon, M. (1990). Entrepreneurial scientist: Organizational performance in scientist-started high technology firms. Forest Park: Frontiers of Entrepreneurship Research, Babson College Entrepreneurship Research Conference (BCERC).Schmitz, A., Urbano, D., Dandolini, G. A., de Souza, J. A., & Guerrero, M. (2017). Innovation and entrepreneurship in the academic setting: A systematic literature review. International Entrepreneurship and Management Journal, 13(2), 369–395.Shane, S., & Khurana, R. (2003). Bringing individuals back in: The effects of career experience on new firm founding. Industrial and Corporate Change, 12, 519–543.Shapero, A., & Sokol, L. (1982). The social dimensions of entrepreneurship. In C. A. Kent, D. L. Sexton, & K. H. Vesper (Eds.), Encyclopaedia of entrepreneurship (pp. 72–90). Englewood Cliffs: Prentice Hall.Smilor, R. W., Gibson, D. V., & Dietrich, G. B. (1990). University spin-out companies: technology start-ups from UT-Austin. Journal of Business Venturing, 5(1), 63–76.Soler i Marco, V. (2009). Creixement i canvi estructural. In V. Soler (Ed.), Economia espanyola i del País Valencià. Valencia: Publicacions de la Universitat de València.Suddaby, R., Bruton, G. D., & Si, S. X. (2015). Entrepreneurship through a qualitative lens: Insights on the construction and/or discovery of entrepreneurial opportunity. Journal of Business Venturing, 30(1), 1–10.Tech Transfer UPV FCR (2016). Air Nostrum, Caixa Popular e IVI entran en el fondo de la UPV. Resource document. TTUPV FCR. http://www.techtransferupv.com/noticias/air-nostrum-caixa-popular-e-ivi-entran-en-el-fondo-de-la-upv/ (4 April) Accessed 10 July 2016.The Times Higher Education (2017). 100 Under 50 Ranking 2017. Resource document. THE. https://www.timeshighereducation.com/world-university-rankings/2017/young-university-rankings#!/page/0/length/-1/sort_by/rank/sort_order/asc/cols/stats . Accessed 15 august 2017.UPV (2007). Instituto IDEAS 15 aniversario (1992–2007). Resource document. UPV. http://www.upv.es/entidades/IDEAS/menu_urlv.html?http://www.upv.es/entidades/IDEAS/info/memoria15a%F1os.pdf . Accessed 10 April 2016.UPV (2011). Corporación empresarial. Resource document. UPV. http://www.upv.es/noticias-upv/noticia-4904-corporacion-emp-es.html . Accessed 10 April 2016.UPV (2014). Plan de emprendimiento global. Resource document. UPV. https://www.upv.es/noticias-upv/noticia-6846-plan-de-emprend-es.html . Accessed 10 April 2016.UPV (2015). Jornadas de Puertas Abiertas 2015–16. Resource document. UPV. www.upv.es/contenidos/ORIENTA/info/jpa_ciclos_2015-16.ppt . Accessed 10 April 2016.UPV (2017a). Spin-Off UPV. Resource document. UPV. http://www.upv.es/entidades/I2T/info/891434normalc.html . Accessed 5 October 2017.UPV (2017b). Ciudad Politécnica de la Innovación. Parque Científico en Red de la Universidad Politécnica de Valencia. Quienes Somos. Presentación. Resource document. UPV. http://cpi.upv.es/quienes-somos/presentacion . Accessed 5 October 2017.UPV (2017c). Servicio de Promoción y Apoyo a la Investigación, la Innovación y la Transferencia. Presentación. Resource document. UPV. http://i2t.webs.upv.es/i2t/presentacion.php. Accessed 5 October 2017 .UPV. (2017d). Tech Transfer UPV. UPV: Resource document http://www.upv.es/noticias-upv/noticia-8355-tech-transfer-u-es.html. Accessed 5 October 2017 .UPV (2017e). Mission statement, vision and values. Resource document. UPV. https://www.upv.es/organizacion/la-institucion/misionvisionvalores-plan-upv-en.html Accessed 17 October 2017.Vargas Vasserot, C. (2012). Las spin-offs académicas y su posible configuración como empresas de economía social. REVESCO. Revista de Estudios Cooperativos, 107, 186–205.VLC/Campus (2017). VLC/Campus. Valencia, International Campus of Excellence. Resource document. UPV. http://www.vlc-campus.com/en . Accessed 5 October 2017.Walter, A., Auer, M., & Ritter, T. (2006). The impact of network capabilities and entrepreneurial orientation on university spin-off performance. Journal of Business Venturing, 21(4), 541–567.Weatherston, J. (1995). Academic Entrepreneurs: Is a spin-off Company too risky. Proceedings of the 40th International Council on Small Business, Sydney, 18–21.Willoughby, M., Talon, J., Millet, J., & Ayats, C. (2013). University services for fostering creativity in hi-tech firms. The Service Industries Journal, 33, 1103–1116.Wright, M., & Mosey, S. (2012). Strategic entrepreneurship, resource orchestration and growing spin-offs from universities. Technology Analysis and Strategic Management, 24, 911–927.Wright, M., Clarysse, B., Mustar, P., & Lockett, A. (2007). Academic Entrepreneurship in Europe. Cheltenham: Edward Elgar.Yin, R. K. (1994). Case study research: Design and methods (2nd ed.). Sage: Thousand Oaks.Yusof, M., & Jain, K. J. (2010). Categories of university-level entrepreneurship: A literature survey. International Entrepreneurship and Management Journal, 6(1), 81–86

E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis

Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response

CDK19 is disrupted in a female patient with bilateral congenital retinal folds, microcephaly and mild mental retardation

Microcephaly, mental retardation and congenital retinal folds along with other systemic features have previously been reported as a separate clinical entity. The sporadic nature of the syndrome and lack of clear inheritance patterns pointed to a genetic heterogeneity. Here, we report a genetic analysis of a female patient with microcephaly, congenital bilateral falciform retinal folds, nystagmus, and mental retardation. Karyotyping revealed a de novo pericentric inversion in chromosome 6 with breakpoints in 6p12.1 and 6q21. Fluorescence in situ hybridization analysis narrowed down the region around the breakpoints, and the breakpoint at 6q21 was found to disrupt the CDK19 gene. CDK19 was found to be expressed in a diverse range of tissues including fetal eye and fetal brain. Quantitative PCR of the CDK19 transcript from Epstein–Barr virus-transformed lymphoblastoid cell lines of the patient revealed ~50% reduction in the transcript (p = 0.02), suggesting haploinsufficiency of the gene. cdk8, the closest orthologue of human CDK19 in Drosophila has been shown to play a major role in eye development. Conditional knock-down of Drosophila cdk8 in multiple dendrite (md) neurons resulted in 35% reduced dendritic branching and altered morphology of the dendritic arbour, which appeared to be due in part to a loss of small higher order branches. In addition, Cdk8 mutant md neurons showed diminished dendritic fields revealing an important role of the CDK19 orthologue in the developing nervous system of Drosophila. This is the first time the CDK19 gene, a component of the mediator co-activator complex, has been linked to a human disease

Nucleolar Proteins Suppress Caenorhabditis elegans Innate Immunity by Inhibiting p53/CEP-1

The tumor suppressor p53 has been implicated in multiple functions that play key roles in health and disease, including ribosome biogenesis, control of aging, and cell cycle regulation. A genetic screen for negative regulators of innate immunity in Caenorhabditis elegans led to the identification of a mutation in NOL-6, a nucleolar RNA-associated protein (NRAP), which is involved in ribosome biogenesis and conserved across eukaryotic organisms. Mutation or silencing of NOL-6 and other nucleolar proteins results in an enhanced resistance to bacterial infections. A full-genome microarray analysis on animals with altered immune function due to mutation in nol-6 shows increased transcriptional levels of genes regulated by a p53 homologue, CEP-1. Further studies indicate that the activation of innate immunity by inhibition of nucleolar proteins requires p53/CEP-1 and its transcriptional target SYM-1. Since nucleoli and p53/CEP-1 are conserved, our results reveal an ancient immune mechanism by which the nucleolus may regulate immune responses against bacterial pathogens

Corporate Entrepreneurship:From Structures to Mindset

Corporate entrepreneurship dispersed throughout an organization and leveraging the entrepreneurial potential of all its employees bears significant benefits for those organizations that embrace it. However, it appears more difficult to instill and requires strong investment in the development of human capital and entrepreneurial mindset among the employees and across the organization. In this chapter, we discuss the essence of corporate entrepreneurship mindset and show that across an organization, there might be different entrepreneurial mindsets that correspond to different people, opportunities, and contexts. Although different, they all lead to enactment of entrepreneurial projects. This chapter, thus, contributes to the discussion regarding the nature of corporate entrepreneurial mindsets, and their development and stimulation within an organization, from both academic and practical view

Entrepreneurship, export orientation and economic growth

In this paper the relationship between a country’s prevalence of new ventures and its rate of economic growth is investigated, while taking into account new ventures’ export orientation. It is generally acknowledged that new venture creation as well as export activity may both be important strategies for achieving national economic growth. However, to our knowledge no attempt has been made to investigate empirically the role of export-driven new ventures in economic growth. We focus on the national level and use data for a sample of 34 countries over the period 2002–2008. Our results suggest that, on top of a positive relation between entrepreneurial activity in general and subsequent macroeconomic growth, there is an additional positive effect of export-oriented early-stage entrepreneurship in higher-income countries. However, there is no such additional effect in lower-income countries

Performance-based vs socially supportive culture:a cross-national study of descriptive norms and entrepreneurship

This paper is a cross-national study testing a framework relating cultural descriptive norms to entrepreneurship in a sample of 40 nations. Based on data from the Global Leadership and Organizational Behavior Effectiveness project, we identify two higher-order dimensions of culture – socially supportive culture (SSC) and performance-based culture (PBC) – and relate them to entrepreneurship rates and associated supply-side and demand-side variables available from the Global Entrepreneurship Monitor. Findings provide strong support for a social capital/SSC and supply-side variable explanation of entrepreneurship rate. PBC predicts demand-side variables, such as opportunity existence and the quality of formal institutions to support entrepreneurship