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Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events. The aim of this study was to investigate the effect of chronic, prenatal LD gamma irradiation to the biology of MSCs later in life. C3H mice were exposed in utero to chronic prenatal irradiation of 10 mGy/day over a period of 3 weeks. Two years later, MSCs were isolated from the bone marrow and analyzed in vitro for their radiosensitivity, for cellular senescence and for DNA double-strand break recognition after a second acute gamma-irradiation. In addition to these cellular assays, changes in protein expression were measured using HPLC–MS/MS and dysregulated molecular signaling pathways identified using bioinformatics. We observed radiation-induced proteomic changes in MSCs from the offspring of in utero irradiated mice (leading to ~ 9.4% of all detected proteins being either up- or downregulated) as compared to non-irradiated controls. The proteomic changes map to regulation pathways involved in the extracellular matrix, the response to oxidative stress, and the Wnt signaling pathway. In addition, chronic prenatal LD irradiation lead to an increased rate of in vitro radiation-induced senescence later in life and to an increased number of residual DNA double-strand breaks after 4 Gy irradiation, indicating a remarkable interaction of in vivo radiation in combination with a second acute dose of in vitro radiation. This study provides the first insight into a molecular mechanism of persistent MSC damage response by ionizing radiation exposure during prenatal time and will help to predict therapeutic safety and efficacy with respect to a clinical application of stem cells. Supplementary Information The online version contains supplementary material available at 10.1007/s00411-021-00925-7.

Reliable data on the effects of chronic prenatal exposure to low dose (LD) of ionizing radiation in humans are missing. There are concerns about adverse long-term effects that may persist throughout postnatal life of the offspring. Due to their slow cell cycle kinetics and life-long residence time in the organism, mesenchymal stem cells (MSCs) are more susceptible to low level genotoxic stress caused by extrinsic multiple LD events. The aim of this study was to investigate the effect of chronic, prenatal LD gamma irradiation to the biology of MSCs later in life. C3H mice were exposed in utero to chronic prenatal irradiation of 10 mGy/day over a period of 3 weeks. Two years later, MSCs were isolated from the bone marrow and analyzed in vitro for their radiosensitivity, for cellular senescence and for DNA double-strand break recognition after a second acute gamma-irradiation. In addition to these cellular assays, changes in protein expression were measured using HPLC–MS/MS and dysregulated molecular signaling pathways identified using bioinformatics. We observed radiation-induced proteomic changes in MSCs from the offspring of in utero irradiated mice (leading to ~ 9.4% of all detected proteins being either up- or downregulated) as compared to non-irradiated controls. The proteomic changes map to regulation pathways involved in the extracellular matrix, the response to oxidative stress, and the Wnt signaling pathway. In addition, chronic prenatal LD irradiation lead to an increased rate of in vitro radiation-induced senescence later in life and to an increased number of residual DNA double-strand breaks after 4 Gy irradiation, indicating a remarkable interaction of in vivo radiation in combination with a second acute dose of in vitro radiation. This study provides the first insight into a molecular mechanism of persistent MSC damage response by ionizing radiation exposure during prenatal time and will help to predict therapeutic safety and efficacy with respect to a clinical application of stem cells.

In prokaryotes, a diverse set of physiological processes is regulated by transcription factors which belong to the well-conserved, enhancer-binding protein (EBP) family. These regulatory proteins function together with the alternate sigma factor (sigma(54)). Structurally, the EBPs are characterized by a central activator domain, containing the recognition motif for the RNA polymerase/sigma(54) complex (Esigma(54)), and the C-terminal domain, containing a DNA-binding helix-turn-helix motif. A regulatory system of the EBP type also exists in Pseudomonas syringae, where it controls the expression of genes required for the induction of disease symptoms and resistance responses in plants. The system consists of the two genes, hrpR and hrpS, which belong to the hrp (hypersensitive response and pathogenicity) gene cluster. The two genes show a high degree of structural and sequence similarities, but function at different positions in the hrp regulatory cascade of the bean pathogen Pseudomonas syringae pv. phaseolicola. In this paper, we were interested in the basis of the difference in specificity between hrpR and hrpS. The functional specificities of the two domains of hrpS and hrpR were analysed by domain switching. Complementation analyses with the hybrid genes and retardation experiments with the protein products showed significant differences between the respective domains of hrpS and hrpR.

Preface:The growth debate, revisited Rita Trattnigg (Austrian Federal Ministry of Agriculture, Forestry, Environment and Water) What kind of growth is sustainable? A presentation of arguments Elke Pirgmaier and Friedrich Hinterberger (Sustainable Europe Research Institute) Part 1: Research perspective Elitist Cheap Labour Policies Stimulate Uneconomic Growth Herman Daly (University of Maryland)Prosperity without Growth Tim Jackson (University of Surrey) Exit Ramp to Sustainability?Juliet Schor (Boston College) China's Economic Growth: Pattern and Limits Yang Cuihong (Chinese Academy of Sciences) Part 2: Policy perspective Growth -- Crisis -- Change: How the financial and energy crises reveal the need for sustainable development Andreas Breitenfellner (European Commission) The EU on the pathway to sustainable growth? Jo Leinen (European Parliament) Advancing eco-innovation as an enabler of decoupling Tomoo Machiba (OECD) The growth path of Europe: sustainable, smart and inclusive Robin Miege (European Commission) Driving growth with new engines Fulai Sheng (UNEP) Economic Fluctuations in Latvia or a Human on the Path of Transformation Mara Zira, Guntars Ruskuls and Agrita Jeruma (Riga City Council) Part 3:Civil society perspective Dispelling the Myths of Growth and Consumerism Erik Assadourian (Worldwatch Institue) A New Economy inspired by Sustainability Science Gianfranco Bologna (WWF Italy) The Tragedy of the Growth-Saga Maja Gopel (World Future Council) There is enough for everyone! On growth and distributional justice Michaela Moser (European Anti Poverty Network) Part 4:Business perspective Dimensions of Sustainable Growth Kurt Bayer (European Bank for Reconstruction and Development) Good-Bye 'Ownership', 'Materialism' and 'Monetization' in Lifestyles: A New Era Dawning in Japan Junko Edahiro (Japan for Sustainability) The Future of Growth Philip Reuchlin (World Business Council for Sustainable Development) What kind of growth is sustainable? Martin Sieker (European Economic and Social Committee)

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