Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression

This study proposes a strategy, based on self-regulation therapy, to change personality and its biological substrate, the DRD3 gene expression. It has been demonstrated that acute doses of stimulating drugs, like methylphenidate, are able to change personality and the expression of certain genes in the short term. On the other hand, self-regulation therapy has been proven to reproduce the effects of drugs. Thus, it is feasible to hope that self-regulation therapy is equally effective as methylphenidate in changing personality and the gene expression. This is a preliminary study with a single-case experimental design with replication in which 2 subjects participated. The results and potential implications for research and psychotherapy are discussed.Amigó Borrás, S.; Caselles Moncho, A.; Micó Ruiz, JC. (2013). Self-Regulation Therapy to Reproduce Drug Effects: A Suggestion Technique to Change Personality and the DRD3 Gene Expression. 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Comparative Analyses of SUV420H1 Isoforms and SUV420H2 Reveal Differences in Their Cellular Localization and Effects on Myogenic Differentiation

Methylation of histone H4 on lysine 20 plays critical roles in chromatin structure and function via mono- (H4K20me1), di- (H4K20me2), and trimethyl (H4K20me3) derivatives. In previous analyses of histone methylation dynamics in mid-gestation mouse embryos, we documented marked changes in H4K20 methylation during cell differentiation. These changes were particularly robust during myogenesis, both in vivo and in cell culture, where we observed a transition from H4K20me1 to H4K20me3. To assess the significance of this change, we used a gain-of-function strategy involving the lysine methyltransferases SUV420H1 and SUV420H2, which catalyze H4K20me2 and H4K20me3. At the same time, we characterized a second isoform of SUV420H1 (designated SUV420H1_i2) and compared the activity of all three SUV420H proteins with regard to localization and H4K20 methylation.Immunofluorescence revealed that exogenous SUV420H1_i2 was distributed throughout the cell, while a substantial portion of SUV420H1_i1 and SUV420H2 displayed the expected association with constitutive heterochromatin. Moreover, SUV420H1_i2 distribution was unaffected by co-expression of heterochromatin protein-1α, which increased the targeting of SUV420H1_i1 and SUV420H2 to regions of pericentromeric heterochromatin. Consistent with their distributions, SUV420H1_i2 caused an increase in H4K20me3 levels throughout the nucleus, whereas SUV420H1_i1 and SUV420H2 facilitated an increase in pericentric H4K20me3. Striking differences continued when the SUV420H proteins were tested in the C2C12 myogenic model system. Specifically, although SUV420H1_i2 induced precocious appearance of the differentiation marker Myogenin in the presence of mitogens, only SUV420H2 maintained a Myogenin-enriched population over the course of differentiation. Paradoxically, SUV420H1_i1 could not be expressed in C2C12 cells, which suggests it is under post-transcriptional or post-translational control.These data indicate that SUV420H proteins differ substantially in their localization and activity. Importantly, SUV420H2 can induce a transition from H4K20me1 to H4K20me3 in regions of constitutive heterochromatin that is sufficient to enhance myogenic differentiation, suggesting it can act an as epigenetic ‘switch’ in this process

Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2

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Guanidine - acylguanidine bioisosteric approach in the design of radioligands: Synthesis of a tritium-labeled N(G)-propionylargininamide ([3H]UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist

Synthesis and characterization of (R)-N(alpha)-(2,2-diphenylacetyl)-N-(4-hydroxybenzyl)-N(omega)-([2,3-3H2]-propanoyl)argininamide ([3H]-UR-MK114), an easily accessible tritium-labeled NPY Y1 receptor (Y1R) antagonist (KB: 0.8 nM, calcium assay, HEL cells) derived from the (R)-argininamide BIBP 3226, is reported. The radioligand binds with high affinity (KD, saturation: 1.2 nM, kinetic experiments: 1.1 nM, SK-N-MC cells) and selectivity for Y1R over Y2, Y4 and Y5 receptors. The title compound is a useful pharmacological tool for the determination of Y1R ligand affinities, quantification of Y1R binding sites and autoradiography