Edited by John M. Denu The building blocks of DNA, dNTPs, can be produced de novo or can be salvaged from deoxyribonucleosides. However, to what extent the absence of de novo dNTP production can be compensated for by the salvage pathway is unknown. Here, we eliminated de novo dNTP synthesis in the mouse heart and skeletal muscle by inactivating ribonucleotide reductase (RNR), a key enzyme for the de novo production of dNTPs, at embryonic day 13. All other tissues had normal de novo dNTP synthesis and theoretically could supply heart and skeletal muscle with deoxyribonucleosides needed for dNTP production by salvage. We observed that the dNTP and NTP pools in WT postnatal hearts are unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse embryos or murine cell cultures. We found that RNR inactivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant DNA replication; defective expression of muscle-specific proteins; progressive heart abnormalities; disturbance of the cardiac conduction system; and lethality between the second and fourth weeks after birth. We conclude that dNTP salvage cannot substitute for de novo dNTP synthesis in the heart and that cardiomyocytes and myocytes initiate DNA replication despite an inadequate dNTP supply. We discuss the possible reasons for the observed asymmetry in dNTP and NTP pools in WT hearts. This work was supported by grants from the Swedish Cancer Society and the Swedish Research Council (to A. C.). The authors declare that they have no conflicts of interest with the contents of this article. This article was selected as one of our Editors' Picks. This article contains Tables S1-S3, Figs. S1-S6, and Movies S1 and S2.
In this chapter, the possibilities to use technology in order to improve the contextual and value-based dimensions in online distance-based teacher training in Sweden are explored. Aristotle’s (1980) concept of phronesis is used as a starting point for raising questions whether the Internet, and the establishing of educational online learning communities, can be used to enhance the teacher trainees´ skills of making moral decisions in unpredictable situations. It is argued that active participation, collaboration, and dialogue are vital in order to foster common moral and societal values among the teacher trainees, but that there is a need for rethinking how technology could be used in order to accommodate such processes. This chapter suggests that the development of a shared teacher identity is possible by expanding the scope of online community, and bridging teacher-training practices to teacher practices, thus including already practicing teachers, teacher trainers, and teacher trainees in a joint educational community.
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