Clinical aspects of a large group of adults with Angelman syndrome

Descriptions of the clinical features of Angelman syndrome (AS) have mainly been focused on children. Here, we describe

Adding cognitive therapy to dietetic treatment is associated with less relapse in obesity

Objective: The treatment of obesity is universally disappointing; although usually some weight loss is reported directly after treatment, eventual relapse to, or even above, former body weight is common. In this study it is tested whether the addition of cognitive therapy to a standard dietetic treatment for obesity might prevent relapse. It is argued that the addition of cognitive therapy might not only be effective in reducing weight and related concerns, depressed mood, and low self-esteem, but also has an enduring effect that lasts beyond the end of treatment. Methods: Non-eating-disordered overweight and obese participants in a community health center (N=204) were randomly assigned to a group dietetic treatment+cognitive therapy or a group dietetic treatment+physical exercise. Results: Both treatments were quite successful and led to significant decreases in BMI, specific eating psychopathology (binge eating, weight-, shape-, and eating concerns) and general psychopathology (depression, low sell-esteem). In the long run, however, the cognitive dietetic treatment was significantly better than the exercise dietetic treatment; participants in the cognitive dietetic treatment maintained all their weight loss, whereas participants in the physical exercise dietetic treatment regained part (25%) of their lost weight. Conclusion: Cognitive therapy had enduring effects that lasted beyond the end of treatment. This potential prophylactic effect of cognitive therapy is promising; it might be a new strategy to combat the global epidemic of obesity. (C) 2009 Elsevier Inc. All rights reserved

Unlike dietary restriction, rapamycin fails to extend lifespan and reduce transcription stress in progeroid DNA repair-deficient mice

Dietary restriction (DR) and rapamycin extend healthspan and life span across multiple species. We have recently shown that DR in progeroid DNA repair-deficient mice dramatically extended healthspan and trippled life span. Here, we show that rapamycin, while significantly lowering mTOR signaling, failed to improve life span nor healthspan of DNA repair-deficient Ercc1( increment /-) mice, contrary to DR tested in parallel. Rapamycin interventions focusing on dosage, gender, and timing all were unable to alter life span. Even genetically modifying mTOR signaling failed to increase life span of DNA repair-deficient mice. The absence of effects by rapamycin on P53 in brain and transcription stress in liver is in sharp contrast with results obtained by DR, and appoints reducing DNA damage and transcription stress as an important mode of action of DR, lacking by rapamycin. Together, this indicates that mTOR inhibition does not mediate the beneficial effects of DR in progeroid mice, revealing that DR and rapamycin strongly differ in their modes of action

Activation of a peroxisomal Pichia pastoris D-amino acid oxidase, which uses D-alanine as a preferred substrate, depends on pyruvate carboxylase

D-Amino acid oxidase (DAO) is an important flavo-enzyme that catalyzes the oxidative deamination of D-amino acids into the corresponding α-keto acid, ammonia and H2O2. We identified two amino acid oxidases in the methylotrophic yeast Pichia pastoris: Dao1p, which preferentially uses D-alanine as a substrate, and Dao2p, which uses D-aspartate as a preferred substrate. Dao1p has a molecular mass of 38.2 kDa and a pH optimum of 9.6. This enzyme was localized to peroxisomes, albeit a typical peroxisomal targeting signal is lacking. Interestingly, P. pastoris mutant strains, defective in the enzyme pyruvate carboxylase, showed a pronounced growth defect on D-alanine, concomitant with a significant reduction in Dao1p activity relative to the wild-type control. This indicates that pyruvate carboxylase functions in import and/or activation of P. pastoris Dao1p.