Differential DNA methylation patterns between high and low responders to a weigh t loss intervention in overweight or obese adolescents:

the EVASYON study Abstract: In recent years, epigenetic markers emerged as a new tool to understan d the influence of lifestyle factors on obesity phenotypes. Adolescence is consi dered an important epigenetic window over a human's lifetime. The objective of t his work was to explore baseline changes in DNA methylation that could be associ ated with a better weight loss response after a multidisciplinary intervention p rogram in Spanish obese or overweight adolescents. Overweight or obese adolescen ts (n=107) undergoing 10 wk of a multidisciplinary intervention for weight loss were assigned as high or low responders to the treatment. A methylation microarr ay was performed to search for baseline epigenetic differences between the 2 gro ups (12 subjects/group), and MALDI-TOF mass spectrometry was used to validate (n =107) relevant CpG sites and surrounding regions. After validation, 5 regions lo cated in or near AQP9, DUSP22, HIPK3, TNNT1, and TNNI3 genes showed differential methylation levels between high and low responders to the multidisciplinary wei ght loss intervention. Moreover, a calculated methylation score was significantl y associated with changes in weight, BMI-SDS, and body fat mass loss after the t reatment. In summary, we have identified 5 DNA regions that are differentially m ethylated depending on weight loss response. These methylation changes may help to better understand the weight loss response in obese adolescents. Moleres, A., C ampin, J., Milagro, F. I., Marcos, A., Campoy, C., Garagorri, J. M., Gmez-Martnez, S., Martnez, J. A., Azcona-Sanjulin, M. C., Mart, A. Differential DNA methylation p atterns between high and low responders to a weight loss intervention in overwei ght or obese adolescents: the EVASYON study. Source: A. Moleres, J. Campion, F. I. Milagro, A. Marcos, C. Campoy, J. M. Gara gorri, S. Gomez-Martinez, J. A. Martinez, M. C. Azcona-Sanjulian, A. Marti. Diff erential DNA methylation patterns between high and low responders to a weight lo ss intervention in overweight or obese adolescents: the EVASYON study. The FASEB Journal, 2013; 27 (6): 2504 DOI: 10.1096/fj.12-215566: Retrieved from URL : htt p://www.fasebj.org/content/27/6/2504 (21 August 2013) Altered Ca2+ Homeostasis and Endoplasmic Reticulum Stress in Myotonic Dystrophy Type 1 Muscle Cells Abstract: The pathogenesis of Myotonic Dystrophy type 1 (DM1) is linked to unsta ble CTG repeats in the DMPK gene which induce the mis-splicing to fetal/neonatal isoforms of many transcripts, including those involved in cellular Ca2+ homeost asis. Here we monitored the splicing of three genes encoding for Ca2+ transporte rs and channels (RyR1, SERCA1 and CACN1S) during maturation of primary DM1 muscl e cells in parallel with the functionality of the Excitation-Contraction (EC) co upling machinery. At 15 days of differentiation, fetal isoforms of SERCA1 and CA CN1S mRNA were significantly higher in DM1 myotubes compared to controls. Parall el functional studies showed that the cytosolic Ca2+ response to depolarization in DM1 myotubes did not increase during the progression of differentiation, in c ontrast to control myotubes. While we observed no differences in the size of int racellular Ca2+ stores, DM1 myotubes showed significantly reduced RyR1 protein l evels, uncoupling between the segregated ER/SR Ca2+ store and the voltage-induce d Ca2+ release machinery, parallel with induction of endoplasmic reticulum (ER) stress markers. In conclusion, our data suggest that perturbed Ca2+ homeostasis, via activation of ER stress, contributes to muscle degeneration in DM1 muscle c ells likely representing a premature senescence phenotype. Source: Botta, A.; Malena, A.; Loro, E.; Del Moro, G.; Suman, M.; Pantic, B.; Sz abadkai, G.; Vergani, L. Altered Ca2+ Homeostasis and Endoplasmic Reticulum Stre ss in Myotonic Dystrophy Type 1 Muscle Cells. Genes 2013, 4, 275-292. Retrieved from URL: http://www.mdpi.com/2073-4425/4/2/275/pdf

Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism Abstract: More than fifteen genetic diseases, including Huntington s disease, myot onic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the ab errant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease pr ogression. DNA damage and base excision repair (BER) are involved in repeat inst ability and might contribute to the tissue selectivity of the process. In this r eview, we will discuss the mechanisms of trinucleotide repeat instability, focus ing more specifically on the role of BER. Source: Goula, A.-V.; Merienne, K. Abnormal Base Excision Repair at Trinucleotid e Repeats Associated with Diseases: A Tissue-Selective Mechanism. Genes 2013, 4, 375-387.: Retrieved from URL: http://www.mdpi.com/2073-4425/4/3/375/pdf