Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities

At the intersection of globalization and "civilizational originality' : cultural production in Putin's Russia

This special issue originates from a transnational collaboration of scholars in philology, comparative literature, social theory, sociology, anthropology, ethnography, and media studies. The collection strives to advance a research agenda built on the nexus of three intellectual and academic domains: post-Soviet Russian cultural studies', the research paradigm put forward by Cultural Studies, as well as empirical methods developed in sociology. The collection illustrates the importance of expanding the experience of Cultural Studies beyond its established spheres of national investigation, while it also speaks to the necessity to re-evaluate the hegemony of the English-language academic and cultural production on the global scale. The collection offers insights into the gamut of cultural practices and institutional environments in which Russian cultural production happens today. It shows how cultural industries and institutions in Russia are integrated into the global marketplace and transnational communities, while they also draw on and contribute to local lives and experiences by trying to create an autonomous space for symbolic production at personal and collective levels. Through diverse topics, the issue sheds light on the agency, i.e. practitioners and participants, creators and consumers, of Russian cultural production and the neoliberal practices implemented on creative work and cultural administration in Russia today. The Introduction outlines the development of academic studies on Russian cultural practices since 1991; describes main political developments shaping the cultural field in Putin's Russia; and, finally, identifies the Cultural Studies debates the editors of the collection find most productive for investigations of Russia, i.e. the instrumentalization of culture and culture as resource. Relocated in an analysis of a post-socialist society, these conceptualisations seem increasingly problematic in a situation where local and federal policies governing cultural and creative work focus simultaneously on marketization and on nationalism as the main tools of legitimizing the federal government.Peer reviewe

Understanding private law. On the work of Hans Nieuwenhuis, 1944-2015

Hans Nieuwenhuis’ work is difficult to capture in a single sentence. It aims to impart an understanding of private law which, Nieuwenhuis says, requires an awareness of time, space and balance. We measure his work by his own yardstick.Coherent privaatrech

Soco-net: Social care community network

Summary: SoCo-net presents a social care network based on an innovative practice-oriented care community model that supports elderly people to remain longer indepenedent by integrating new types of advance elderly social interaction with new ways of formal and informal care provision. Objective: The main aim is to organize around the elderly personalized Virtual Collaborative Care Teams, consisiting of formal and informal carers, that can actively collaborate to provide ICT based elderly care in the areas of care & wellness, guidance and mobility assistance services. It focuses on end-users wishes and needs in terms of what factors, relationships and communication issues are meaningful and generate the greatest impact on the elderly self care. Methodology: Focus groups, structured interviews and questionnaires were applied to identify the elderly socialization needs and wishes and use case scenarios were formulated. The solution was validated by a sample of 100 end-users (including elderly, formal and informal care professionals) by the Orbis Medical & Care Group, in Netherlands. Results: Based on the analysis performed on the validation results, 72% of the elderly and 100% of the care professionals find it very easy to use (even without guidance). Also 84% of the elderly and 100% of the care professionals find it very useful and said that it can significantly improve their quality of life

Hoe begrip van burgerlijk recht mogelijk is. Over het werk van Hans Nieuwenhuis

Het werk van Hans Nieuwenhuis is moeilijk in één zin te vatten. Het beoogt begrip bij te brengen van burgerlijk recht. Daarvoor is volgens Nieuwenhuis ruimte- en tijdsbesef nodig, en weegvermogen. Wij leggen zijn werk langs die zelfgekozen meetlat.Coherent privaatrech