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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Toxoplasma gondii gene expression is under the control of regulatory pathways acting through chromatin structure.

International audienceThe activity state of a gene is determined by a complex regulatory network of co-acting factors affecting the structure of the chromatin into which the gene is embedded. While significant changes of the transcriptome occur during cell differentiation in apicomplexan parasites, basic mechanisms controlling gene expression are still unknown. Recent studies support and expand the concept of the chromatin environment being key factor for the control of transcriptional activity in these lower eukaryotes organisms. Here, we review recent advances in the field of epigenetic gene regulation in Toxoplasma gondii, the model apicomplexan

SET8-Mediated Methylations of Histone H4 Lysine 20 Mark Silent Heterochromatic Domains in Apicomplexan Genomes.

International audiencePost-translational histone modifications modulate chromatin-templated processes in various biological systems. H4K20 methylation is considered to have an evolutionary ancient role in DNA repair/genome integrity, while its function in heterochromatin function/gene expression is thought to have arisen later during evolution. Here, we identify and characterize H4K20 methylases of the Set8 family in Plasmodium and Toxoplasma, two medically-important members of the Apicomplexan phylum of protozoa. Remarkably, parasite Set8-related proteins display H4K20 mono-, di- and trimethylase activity in striking contrast with the mono-methylase restricted human Set8. Structurally, few residues forming the substrate-specific channel dictate the enzyme methylation multiplicity. These enzymes are cell cycle regulated and focally enriched at pericentric and telomeric heterochromatin in both parasites. Collectively, our findings provide new insights into the evolution of Set8-mediated biochemical pathways suggesting that the heterochromatic function of the mark is not restricted to metazoans. Thus, these lower eukaryotes have developed a diverse panel of biological stages through their high capacity to differentiate and epigenetics only begins to emerge as a strong determinant of their biology

Discovery of holoenzyme-disrupting chemicals as substrate-selective CK2 inhibitors.

CK2 is a constitutively active protein kinase overexpressed in numerous malignancies. Interaction between CK2α and CK2β subunits is essential for substrate selectivity. The CK2α/CK2β interface has been previously targeted by peptides to achieve functional effects; however, no small molecules modulators were identified due to pocket flexibility and open shape. Here we generated numerous plausible conformations of the interface using the fumigation modeling protocol, and virtually screened a compound library to discover compound 1 that suppressed CK2α/CK2β interaction in vitro and inhibited CK2 in a substrate-selective manner. Orthogonal SPR, crystallography, and NMR experiments demonstrated that 4 and 6, improved analogs of 1, bind to CK2α as predicted. Both inhibitors alter CK2 activity in cells through inhibition of CK2 holoenzyme formation. Treatment with 6 suppressed MDA-MB231 triple negative breast cancer cell growth and induced apoptosis. Altogether, our findings exemplify an innovative computational-experimental approach and identify novel non-peptidic inhibitors of CK2 subunit interface disclosing substrate-selective functional effects

Definition of therapeutic response criteria using MRI in Crohn's disease patients treated with anti-TNF therapy: a multicenter prospective study (the IRMA study)

International audienc