Developmental maturation

Abstract: To the Editor.— In his article, published in the July 1987 issue of the Archives, Weinberger1presents an intriguing and heuristically rich model of hypothesized interaction between prefrontal cortical and mesolimbic dopamine systems in schizophrenia. This model is consistent with a great deal of evidence that has accumulated with regard to schizophrenia, including, crucially, the timing of its onset in terms of developmental maturation within the central nervous system. Weinberger's is the latest of a series of structural versions of the "diathesis" in the stress-diathesis model of schizophrenia.2 Weinberger notes that the structural lesion in such a model does not necessarily imply the existence of a distinct, discontinuous biologic subgroup. The "schizophrenia lesion" in such a model could possibly be no more than the extreme end of a developmental spectrum with regard to the organization of a particular central nervous system functional system, such as the hypothesized abnormality

Abstract: Informed consent should be seen as an essential part of health care practice; parental permission and childhood assent is an active process that engages patients, both adults and children, in their health care. Pediatric practice is unique in that developmental maturation allows, over time, for increasing inclusion of the child's and adolescent's opinion in medical decision-making in clinical practice and research. This technical report, which accompanies the policy statement "Informed Consent in Decision-Making in Pediatric Practice" was written to provide a broader background on the nature of informed consent, surrogate decision-making in pediatric practice, information on child and adolescent decision-making, and special issues in adolescent informed consent, assent, and refusal. It is anticipated that this information will help provide support for the recommendations included in the policy statement.

Abstract: We previously reported that primordial germ cells (PGCs) in mice erase genome-wide DNA methylation and histone H3 lysine9 dimethylation (H3K9me2), and instead acquire high levels of tri-methylation of H3K27 (H3K27me3) during their migration, a process that might be crucial for the re-establishment of potential totipotency in the germline. We here explored a cellular dynamics associated with this epigenetic reprogramming. We found that PGCs undergo erasure of H3K9me2 and upregulation of H3K27me3 in a progressive, cell-by-cell manner, presumably depending on their developmental maturation. Before or concomitant with the onset of H3K9 demethylation, PGCs entered the G2 arrest of the cell cycle, which apparently persisted until they acquired high H3K27me3 levels. Interestingly, PGCs exhibited repression of RNA polymerase II-dependent transcription, which began after the onset of H3K9me2 reduction in the G2 phase and tapered off after the acquisition of high-level H3K27me3. The epigenetic reprogramming and transcriptional quiescence were independent from the function of Nanos3. We found that before H3K9 demethylation, PGCs exclusively repress an essential histone methyltransferase, GLP, without specifically upregulating histone demethylases. We suggest the possibility that active repression of an essential enzyme and subsequent unique cellular dynamics ensures successful implementation of genome-wide epigenetic reprogramming in migrating PGCs.