Don't Just Do Something, Sit There: Helping Others Become More Strategic, Conceptual, and Creative: A Cooperative Inquiry

How can we be more effective in helping others become more strategic, conceptual, and creative in their thinking? This group was motivated by the realization that as organizers, they could teach organizing, but were not good at getting people to think strategically. Doing cooperative inquiry gave them a space to challenge each other's assumptions about organizing, ask provocative questions and learn from one another. During their inquiry, the group started to change the way they worked in their organizations, trying new methods to engage people, such as story telling, metaphors, and other methods that allowed them to encourage participation and reflective practices. In the words of the group ""a gradual, but profound, shift occurred in our assumptions about developing leaders for our organizations."" Through their inquiry the group began to understand that the key issue is to engage others in the experience of strategic thinking. ""We realized that...in order to help people learn to be more strategic, creative, and conceptual, we would have to be intentional about being more strategic, creative, and conceptual in our relationship with them

Building a community of self-motivated learners : strategies to help students thrive in school and beyond/ Ferlazzo

xvi, 199 p.: tab.; 25 cm

Building a community of self-motivated learners : strategies to help students thrive in school and beyond/ Ferlazzo

xvi, 199 p.: tab.; 25 cm

Fast and binary assay for predicting radiosensitivity based on the nucleoshuttling of ATM protein: development, validation and performances

International audiencePurposeThe societal and clinical impact of post-radiotherapy adverse tissue events (AE) has highlighted the need of molecular parameters to predict individual radiosensitivity. Recent studies have stressed the role of the phosphorylated forms of the ATM protein (pATM) and its nucleoshuttling in response to radiation. The statistical performance of the pATM immunofluorescence assay to predict AE is promising. However, immunofluorescence requires a time-consuming amplification of cells. The purpose of this study was to develop a predictive assay based on the ELISA technique that renders faster the previous approach.Materials and methodsThis study was performed on 30 skin fibroblasts from 9 radioresistant and 21 AE patients. Patients were divided in 2 groups, radioresistant (toxicity grade<2) and radiosensitive (toxicity grade ≥2). The quantity of nuclear pATM molecules was assessed by ELISA method at 10 min and 1 h after 2 Gy and compared to pATM immunofluorescence data.ResultsThe pATM ELISA data were found in quantitative agreement with the immunofluorescence ones. A ROC analysis was applied first to two data sets (a training (n=14) and a validating (n=16) one) and thereafter to the whole data with a 2-fold cross-validation method. The assay showed an AUC value higher than 0.8, a sensitivity of 0.8 and a specificity ranging from 0.75 and 1, which strongly document the predictive power of the pATM ELISA assay.ConclusionThis study showed that the assessment of nuclear pATM quantity after 2 Gy via ELISA technique can be the basis of a predictive assay with the highest statistical performance among the available predictive approaches

DNA Double-Strand Breaks Induced in Human Cells by Twelve Metallic Species: Quantitative Inter-Comparisons and Influence of the ATM Protein

Despite a considerable amount of data, the molecular and cellular bases of the toxicity due to metal exposure remain unknown. Recent mechanistic models from radiobiology have emerged, pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition and the repair of DNA double-strand breaks (DSB) and the final response to genotoxic stress. In order to document the role of ATM-dependent DSB repair and signalling after metal exposure, we applied twelve different metal species representing nine elements (Al, Cu, Zn Ni, Pd, Cd, Pb, Cr, and Fe) to human skin, mammary, and brain cells. Our findings suggest that metals may directly or indirectly induce DSB at a rate that depends on the metal properties and concentration, and tissue type. At specific metal concentration ranges, the nucleo-shuttling of ATM can be delayed which impairs DSB recognition and repair and contributes to toxicity and carcinogenicity. Interestingly, as observed after low doses of ionizing radiation, some phenomena equivalent to the biological response observed at high metal concentrations may occur at lower concentrations. A general mechanistic model of the biological response to metal exposure based on the nucleo-shuttling of ATM is proposed to describe the metal-induced stress response and to define quantitative endpoints for toxicity and carcinogenicity

Influence of Linear Energy Transfer on the Nucleo-shuttling of the ATM Protein: A Novel Biological Interpretation Relevant for Particles and Radiation

International audiencePurposeLinear energy transfer (LET) plays an important role in radiation response. Recently, the radiation-induced nucleo-shuttling of ATM from cytoplasm to the nucleus was shown to be a major event of the radiation response that permits a normal DNA double-strand break (DSB) recognition and repair. Here, we aimed to verify the relevance of the ATM nucleo-shuttling model for high-LET particles and various radiation types.Methods and MaterialsATM- and H2AX-immunofluorescence was used to assess the number of recognized and unrepaired DSB in quiescent fibroblast cell lines exposed to x-rays, γ-rays, 9- and 12-MeV electrons, 3- and 65-MeV protons and 75-MeV/u carbon ions.ResultsThe rate of radiation-induced ATM nucleo-shuttling was found to be specific to each radiation type tested. By increasing the permeability of the nuclear membrane with statin and bisphosphonates, 2 fibroblast cell lines exposed to high-LET particles were shown to be protected by an accelerated ATM nucleo-shuttling.ConclusionsOur findings are in agreement with the conclusion that LET and the radiation/particle type influence the formation of ATM monomers in cytoplasm that are required for DSB recognition. A striking analogy was established between the DSB repair kinetics of radioresistant cells exposed to high-LET particles and that of several radiosensitive cells exposed to low-LET radiation. Our data show that the nucleo-shuttling of ATM provides crucial elements to predict radiation response in human quiescent cells, whatever the LET value and their radiosensitivity