The defect in the AT-like hamster cell mutants is complemented by mouse chromosome 9 but not by any of the human chromosomes

X-ray-sensitive Chinese hamster V79 cells mutants, V-C4, V-E5 and V-G8, show an abnormal response to X-ray-induced DNA damage. Like ataxia telangiectasia (AT) cells, they display increased cell killing, chromosomal instability and a diminished inhibition of DNA synthesis following ionizing radiation. To localize the defective hamster gene (XRCC8) on the human genome, human chromosomes were introduced into the AT-like hamster mutants, by microcell mediated chromosome transfer. Although, none of the human chromosomes corrected the defect in these mutants, the defect was corrected by a single mouse chromosome, derived from the A9 microcell donor cell line. In four independent X-ray-resistant microcell hybrid clones of V-E5, the presence of the mouse chromosome was determined by fluorescent in situ hybridization, using a mouse cot-1 probe. By PCR analysis with primers specific for different mouse chromosomes and Southern blot analysis with the mouse Ldlr probe, the mouse chromosome 9, was identified in all four X-ray-resistant hybrid clones. Segregation of the mouse chromosome 9 from these hamster-mouse microcell hybrids led to the loss of the regained X-ray-resistance, confirming that mouse chromosome 9 is responsible for complementation of the defect in V-E5 cells. The assignment of the mouse homolog of the ATM gene to mouse chromosome 9, and the presence of this mouse chromosome only in the radioresistant hamster cell hybrids suggest that the hamster AT-like mutants are homologous to AT, although they are not complemented by human chromosome 11

Meaning-making in a context of climate change : Supporting agency and political engagement

Responding effectively to climate change requires an understanding of what shapes people’s individual and collective sense of agency and responsibility towards the future. It also requires transforming this understanding into political engagement to support systems change. Based on a national representative survey in Sweden (N = 1,237), this research uses the novel SenseMaker methodology to look into these matters. More specifically, in order to understand the social and institutional prerequisites that must be in place to develop inclusive climate responses, we investigate how citizens perceive their everyday life and future, and the implications for their sense of responsibility, agency, and political engagement. Our research findings show how citizens perceive and act on climate change (individually, cooperatively, and by supporting others), their underlying values, beliefs, emotions and paradigms, inter-group variations, and obstacles and enablers for change. The findings reveal that, in general, individual and public climate action is perceived as leading to improved (rather than reduced) wellbeing and welfare. At the same time, climate anxiety and frustration about structural and governance constraints limit agency, whilst positive emotions and inner qualities, such as human–nature connections, support both political engagement and wellbeing. Our results shed light on individual, collective, and structural capacities that must be supported to address climate change. They draw attention to the need to develop new forms of citizen involvement and of policy that can explicitly address these human interactions, inner dimensions of thinking about and acting on climate change, and the underlying social paradigms. We conclude with further research needs and policy recommendations

Meaning-making in a context of climate change: supporting agency and political engagement

Responding effectively to climate change requires an understanding of what shapes people’s individual and collective sense of agency and responsibility towards the future. It also requires transforming this understanding into political engagement to support systems change. Based on a national representative survey in Sweden (N = 1,237), this research uses the novel SenseMaker methodology to look into these matters. More specifically, in order to understand the social and institutional prerequisites that must be in place to develop inclusive climate responses, we investigate how citizens perceive their everyday life and future, and the implications for their sense of responsibility, agency, and political engagement. Our research findings show how citizens perceive and act on climate change (individually, cooperatively, and by supporting others), their underlying values, beliefs, emotions and paradigms, inter-group variations, and obstacles and enablers for change. The findings reveal that, in general, individual and public climate action is perceived as leading to improved (rather than reduced) wellbeing and welfare. At the same time, climate anxiety and frustration about structural and governance constraints limit agency, whilst positive emotions and inner qualities, such as human–nature connections, support both political engagement and wellbeing. Our results shed light on individual, collective, and structural capacities that must be supported to address climate change. They draw attention to the need to develop new forms of citizen involvement and of policy that can explicitly address these human interactions, inner dimensions of thinking about and acting on climate change, and the underlying social paradigms. We conclude with further research needs and policy recommendations. In general, citizens perceive increased individual and public climate action as leading to improved (rather than reduced) wellbeing and welfare.Effective responses to climate change require addressing underlying social paradigms (to complement predominant external, technological, and information-based approaches).Such responses include increasing policy support for: o learning environments and practices that can help individuals to discover internalized social patterns and increase their sense of agency and interconnection (to self, others, nature);o institutional and political mechanisms that support citizen engagement and the systematic consideration of human inner dimensions (values, beliefs, emotions and associated inner qualities/capacities) across all sectors of work, by systematically revising organizations’ vision statements, communication and project management tools, working structures, policies, regulations, human and financial resource allocation, and collaboration; ando nature-based solutions and other approaches to support the human–nature connection. In general, citizens perceive increased individual and public climate action as leading to improved (rather than reduced) wellbeing and welfare. Effective responses to climate change require addressing underlying social paradigms (to complement predominant external, technological, and information-based approaches). Such responses include increasing policy support for: o learning environments and practices that can help individuals to discover internalized social patterns and increase their sense of agency and interconnection (to self, others, nature);o institutional and political mechanisms that support citizen engagement and the systematic consideration of human inner dimensions (values, beliefs, emotions and associated inner qualities/capacities) across all sectors of work, by systematically revising organizations’ vision statements, communication and project management tools, working structures, policies, regulations, human and financial resource allocation, and collaboration; ando nature-based solutions and other approaches to support the human–nature connection. o learning environments and practices that can help individuals to discover internalized social patterns and increase their sense of agency and interconnection (to self, others, nature); o institutional and political mechanisms that support citizen engagement and the systematic consideration of human inner dimensions (values, beliefs, emotions and associated inner qualities/capacities) across all sectors of work, by systematically revising organizations’ vision statements, communication and project management tools, working structures, policies, regulations, human and financial resource allocation, and collaboration; and o nature-based solutions and other approaches to support the human–nature connection.</p

Is cancer progression caused by gradual or simultaneous acquisitions of new chromosomes?

Abstract Background Foulds defined, “Tumor progression (as a) permanent, irreversible qualitative change in one or more of its characters” (Cancer Res. 1954). Accordingly progressions, such as metastases and acquired drug-resistance, were since found to be subspecies of cancers with conserved and numerous new chromosomes. Here we ask whether cancers acquire numerous new chromosomes gradually or simultaneously in progressions. The currently prevailing theory of Nowell (Science, 1976) holds that unexplained “genetic instability” generates “variant sublines (with) changes in chromosome number” and that “clonal” progressions arise by “stepwise selection of more aggressive sublines”. The literature, however, contains many examples of “immediate” selections of progressions with numerous new chromosomes - notably experimentally initiated fusions between cancers and heterologous cells. Furthermore, the stepwise progression theory predicts intermediate sublines of cancers with multiple non-clonal additions of new chromosomes. However, the literature does not describe such intermediates. Results In view of these inconsistencies with stepwise progression we test here a saltational theory, in which the inherent variability of cancer-specific aneuploidy generates “immediate” progressions with individual clonal karyotypes, transcriptomes and phenotypes in single steps. Using cell fusion as an established controllable model of “immediate” progression, we generated seven immortal murine hybridomas by fusing immortal murine myeloma cells and normal antibody-producing B-cells with polyethylene glycol within a few minutes. These immortal hybridomas contained individual sets of 71 to 105 clonal chromosomes, compared to the 52 chromosomes of the parental myeloma. Thus the myeloma had gained 19 to 53 new clonal chromosomes in seven individual hybridomas in a single step. Furthermore, no stable intermediates were found, as would be predicted by a saltational process. Conclusions We conclude that random fusions between myelomas and normal B-cells generate clonal hybridomas with multiple, individual chromosomes in single steps. Similar single-step mechanisms may also generate the “late” clonal progressions of cancers with gains of numerous new chromosomes and thus explain the absence of intermediates. Latency would reflect the low probability of rare stochastic progressions. In conclusion, the karyotypic clonality of hybridomas and spontaneous progressions suggests karyotypic alterations as proximate causes of neoplastic progressions. Since cancer-specific aneuploidy catalyzes karyotypic variation, the degree of aneuploidy predicts the clinical risk of neoplastic progression, confirming classical predictions based on DNA content