We show here that c‐Myc antagonizes the cyclin‐dependent kinase (CDK) inhibitor p27Kip1. p27 expressed from recombinant retroviruses in Rat1 cells associated with and inhibited cyclin E/CDK2 complexes, induced accumulation of the pRb and p130 proteins in their hypophosphorylated forms, and arrested cells in G1. Prior expression of c‐Myc prevented inactivation of cyclin E/CDK2 as well as dephosphorylation of pRb and p130, and allowed continuous cell proliferation in the presence of p27. This effect did not require ubiquitin‐mediated degradation of p27. Myc altered neither the susceptibility of cyclin E/CDK2 to inhibition by p27, nor the intrinsic CDK‐inhibitory activity of p27, but induced sequestration of p27 in a form unable to bind cyclin E/CDK2. Neither Myc itself nor other G1‐cyclin/CDK complexes were directly responsible for p27 sequestration. Retroviral expression of G1 cyclins (D1–3, E or A) or of the Cdc25A phosphatase did not overcome p27‐induced arrest. Growth rescue by Myc required dimerization with Max, DNA binding and an intact transcriptional activation domain, as previously shown for cellular transformation. We propose that this activity is mediated by the product of an as yet unknown Myc‐Max target gene(s) and represents an essential aspect of Myc's mitogenic and oncogenic functions.
Research in the area of robotics has made available numerous possibilities for further innovation in the education of children, especially in the rehabilitation of those with learning difficulties and/or intellectual disabilities. Despite the scientific evidence, there is still a strong scepticism against the use of robots in the fields of education and care of people. Here we present a study on the acceptance of robots by experienced practitioners (specialized in the treatment of intellectual disabilities) and university students in psychology and education sciences (as future professionals). The aim is to examine the factors, through the Unified Theory of Acceptance and Use of Technology (UTAUT) model, that may influence the decision to use a robot as an instrument in the practice. The overall results confirm the applicability of the model in the context of education and care of children, and suggest a positive attitude towards the use of the robot. The comparison highlights some scepticism among the practitioners, who perceive the robot as an expensive and limited tool, while students show a positive perception and a significantly higher willingness to use the robot. From this experience, we formulate the hypothesis that robots may be accepted if more integrated with standard rehabilitation protocols in a way that benefits can outweigh the costs.
The risk posed by complex chemical mixtures in the environment to wildlife and humans is increasingly debated, but has been rarely tested under environmentally relevant scenarios. To address this issue, two mixtures of 14 or 19 substances of concern (pesticides, pharmaceuticals, heavy metals, polyaromatic hydrocarbons, a surfactant, and a plasticizer), each present at its safety limit concentration imposed by the European legislation, were prepared and tested for their toxic effects. The effects of the mixtures were assessed in 35 bioassays, based on 11 organisms representing different trophic levels. A consortium of 16 laboratories was involved in performing the bioassays. The mixtures elicited quantifiable toxic effects on some of the test systems employed, including i) changes in marine microbial composition, ii) microalgae toxicity, iii) immobilization in the crustacean Daphnia magna, iv) fish embryo toxicity, v) impaired frog embryo development, and vi) increased expression on oxidative stress-linked reporter genes. Estrogenic activity close to regulatory safety limit concentrations was uncovered by receptor-binding assays. The results highlight the need of precautionary actions on the assessment of chemical mixtures even in cases where individual toxicants are present at seemingly harmless concentrations.
Introduction Hyperlactatemia during cardiopulmonary bypass is relatively frequent and is associated with an increased postoperative morbidity. The aim of this study was to determine which perfusion-related factors may be responsible for hyperlactatemia, with specific respect to hemodilution and oxygen delivery, and to verify the clinical impact of hyperlactatemia during cardiopulmonary bypass in terms of postoperative morbidity and mortality rate.
We studied 316 patients undergoing cardiopulmonary bypass for coronary artery surgery in order to determine perioperative risk factors for postoperative renal dysfunction. A preliminary univariate analysis was performed by chi 2 analysis for categorical data and Mann-Whitney U-test for continuous variables to detect significant correlations between each risk factor and the occurrence of moderate or severe renal dysfunction. Subsequently, a multiple logistic regression was applied to the three risk factors identified as predictive for severe renal dysfunction. Low cardiac output syndrome and need for banked blood transfusions combined with a low haematocrit value during cardiopulmonary bypass increase the probability of severe renal dysfunction in the postoperative course.
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