Search

IRIS (Interests and Recruitment in Science; http://iris.fp-7.org/about-iris/) is a European 7th framework project focusing on the challenge that only few young people in general, and women in particular, choose an education and career in science and technology. Project IRIS aims to contribute to the improvement of recruitment, retention and gender equity patterns in higher education. To acquire information about the factors that influence the educational choice of young people, a questionnaire was developed by the IRIS consortium. The IRIS questionnaire is based on the model of achievement-related choices (Eccles, Barber, & Jozefowicz, 1999) and on the theory on the role of self-efficacy beliefs (Bandura, 1997). These theories provide a framework for investigating the central aspects that influence an individual's educational choice. This paper reports the experience and findings of the IRIS survey conducted in Austria and Germany. The data are based on a questionnaire survey with 3680 first-year students. Additionally, interview data from Austrian biology students contribute qualitative data about supportive and hindering factors that influences the study choice. The findings indicate that experiences in the secondary school and good teachers are important in choosing a STEM study. To prevent drop-out key factors are relevance of the study choice for the own life, social and academic integration and supportive mentoring systems.

Rhabdomyosarcoma is the most common pediatric soft tissue tumor, comprising two major subtypes: the PAX3/7-FOXO1 fusion-negative embryonal and the PAX3/7-FOXO1 fusion-positive alveolar subtype. Here, we demonstrate that the expression levels of the transcriptional repressor TRPS1 are specifically enhanced in the embryonal subtype, resulting in impaired terminal myogenic differentiation and tumor growth. During normal myogenesis, expression levels of TRPS1 have to decrease to allow myogenic progression, as demonstrated by overexpression of TRPS1 in myoblasts impairing myotube formation. Consequentially, myogenic differentiation in embryonal rhabdomyosarcoma in vitro as well as in vivo can be achieved by reducing TRPS1 levels. Furthermore, we show that TRPS1 levels in RD cells, the bona fide model cell line for embryonal rhabdomyosarcoma, are regulated by miR-1 and that TRPS1 and MYOD1 share common genomic binding sites. The myogenin (MYOG) promoter is one of the critical targets of TRPS1 and MYOD1; we demonstrate that TRPS1 restricts MYOG expression and thereby inhibits terminal myogenic differentiation. Therefore, reduction of TRPS1 levels in embryonal rhabdomyosarcoma might be a therapeutic approach to drive embryonal rhabdomyosarcoma cells into myogenic differentiation, thereby generating postmitotic myotubes., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The distribution of the high concentrations of arsenic (As) and fluoride (F - ) in groundwater on a Pan-European scale could be explained by the geological European context (lithology and structural faults). To test this hypothesis, seventeen countries and eighteen geological survey organizations (GSOs) have participated in the dataset. The methodology has used the HydroGeoToxicity (HGT) and the Baseline Concentration (BLC) index. The results prove that most of the waters considered in this study are in good conditions for drinking water consumption, in terms of As and/or F - content. A low proportion of the analysed samples present HGT≥ 1 levels (4% and 7% for As and F - , respectively). The spatial distribution of the highest As and/or F - concentrations (via BLC values) has been analysed using GIS tools. The highest values are identified associated with fissured hard rock outcrops (crystalline rocks) or Cenozoic sedimentary zones, where basement fractures seems to have an obvious control on the distribution of maximum concentrations of these elements in groundwaters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The two transcriptional coactivators YAP/TAZ act as the downstream transducers of the Hippo pathway. Recent studies have demonstrated that those two transcriptional regulators are crucial for an organism in order to induce a regenerative response upon tissue damage. In addition, YAP/TAZ are promising targets for regenerative medicine, as artificially increasing YAP/TAZ activity can be used to stimulate tissue regeneration, even in tissues that otherwise have little ability to regenerate. We will summarize here how YAP/TAZ could be used in regenerative medicine and how these two transcriptional regulators have been linked to aging so far., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Promoting Responsible Research and Innovation (RRI) is a major strategy of the "Science with and for Society" work program of the European Union's Horizon 2020 Framework Programme for Research and Innovation. RRI aims to achieve a better alignment of research and innovation with the values, needs, and expectations of society. The RRI strategy includes the "keys" of public engagement, open access, gender, ethics, and science education. The Structural Transformation to Attain Responsible BIOSciences (STARBIOS2) project promotes RRI in 6 European research institutions and universities from Bulgaria, Germany, Italy, Slovenia, Poland, and the United Kingdom, in partnership with a further 6 institutions from Brazil, Denmark, Italy, South Africa, Sweden, and the United States., Objective: The project aims to attain RRI structural change in 6 European institutions by implementing action plans (APs) and developing APs for 3 non-European institutions active in the field of biosciences; use the implementation of APs as a learning process with a view to developing a set of guidelines on the implementation of RRI; and develop a sustainable model for RRI in biosciences., Methods: The project comprises interrelated research and implementation designed to achieve the aforementioned specific objectives. The project is organized into 6 core work packages and 5 supporting work packages. The core work packages deal with the implementation of institutional APs in 6 European institutions based on the structural change activation model. The supporting work packages include technical assistance, learning process on RRI-oriented structural change, monitoring and assessment, communication and dissemination, and project management., Results: The project is funded by Horizon 2020 and will run for 4 years (May 2016-April 2020). As of June 2018, the initial phase has been completed. The participating institutions have developed and approved APs and commenced their implementation. An observation tool has been launched by the Technical Assistance Team to collect information from the implementation of APs; the Evaluation & Assessment team has started monitoring the advancement of the project. As part of the communication and dissemination strategy, a project website, a Facebook page, and a Twitter account have been launched and are updated periodically. The International Scientific Advisory Committee has been formed to advise on the reporting and dissemination of the project's results., Conclusions: In the short term, we anticipate that the project will have a considerable impact on the organizational processes and structures, improving the RRI uptake in the participating institutions. In the medium term, we expect to make RRI-oriented organizational change scalable across Europe by developing guidelines on RRI implementation and an RRI model in biosciences. In the long term, we expect that the project would help increase the ability of research institutions to make discoveries and innovations in better alignment with societal needs and values., International Registered Report Identifier (irrid): DERR1-10.2196/11745., (©Vittorio Colizzi, Daniele Mezzana, Pavel V Ovseiko, Giovanni Caiati, Claudia Colonnello, Andrea Declich, Alastair M Buchan, Laurel Edmunds, Elena Buzan, Luiz Zerbini, Dimitar Djilianov, Evanthia Kalpazidou Schmidt, Krzysztof P Bielawski, Doris Elster, Maria Salvato, Luiz C Jr Alcantara, Antonella Minutolo, Marina Potestà, Elena Bachiddu, Maria J Milano, Lorna R Henderson, Vasiliki Kiparoglou, Phoebe Friesen, Mark Sheehan, Daniela Moyankova, Krasimir Rusanov, Martha Wium, Izabela Raszczyk, Igor Konieczny, Jerzy P Gwizdala, Karol Śledzik, Tanja Barendziak, Julia Birkholz, Nicklas Müller, Jürgen Warrelmann, Ute Meyer, Juliane Filser, Fernanda Khouri Barreto, Carla Montesano. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 07.03.2019.)

In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: "This work was supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC001144), the UK Medical Research Council (FC001144), and the Wellcome Trust (FC001144)." https://doi.org/10.1038/s41467-018-05370-7 .

Yes-associated protein (YAP), the downstream transducer of the Hippo pathway, is a key regulator of organ size, differentiation and tumorigenesis. To uncover Hippo-independent YAP regulators, we performed a genome-wide CRISPR screen that identifies the transcriptional repressor protein Trichorhinophalangeal Syndrome 1 (TRPS1) as a potent repressor of YAP-dependent transactivation. We show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. TRPS1 represses YAP-dependent function by recruiting a spectrum of corepressor complexes to joint sites. Loss of TRPS1 leads to activation of enhancers due to increased H3K27 acetylation and an altered promoter-enhancer interaction landscape. TRPS1 is commonly amplified in breast cancer, which suggests that restrained YAP activity favours tumour growth. High TRPS1 activity is associated with decreased YAP activity and leads to decreased frequency of tumour-infiltrating immune cells. Our study uncovers TRPS1 as an epigenetic regulator of YAP activity in breast cancer.

c-Myc (MYC) is an oncogenic transcription factor that is commonly overexpressed in a wide variety of human tumors. In breast cancer, MYC has recently been linked to the triple-negative subtype, a subtype that lacks any targeted therapy. Previously, we demonstrated that MYC behaves as a potent repressor of YAP and TAZ, 2 transcriptional coactivators that function as downstream transducers of the Hippo pathway. In this previous study, MYC repressed YAP/TAZ not only in primary breast epithelial cells but also in mouse models of triple-negative tumors. Here, we extend our previous bioinformatic and experimental analyses and demonstrate that MYC deregulation in primary breast epithelial cells leads to a robust repression of TEAD transcription factor activity, the transcription factor family mainly responsible for YAP/TAZ recruitment. Surprisingly, we find that MYC and TEAD activity is able to stratify different breast cancer subtypes in large panels of breast cancer patients. Thus, a deep understanding of the MYC-YAP/TAZ circuitry might yield new insights into the establishment and maintenance of specific breast cancer subtypes.