In many animals, the germ plasm segregates germline from soma during early development. Oskar protein is known for its ability to induce germ plasm formation and germ cells in Drosophila. However, the molecular basis of germ plasm formation remains unclear. Here, we show that Oskar is an RNA-binding protein in vivo, crosslinking to nanos, polar granule component, and germ cell-less mRNAs, each of which has a role in germline formation. Furthermore, we present high-resolution crystal structures of the two Oskar domains. RNA-binding maps in vitro to the C-terminal domain, which shows structural similarity to SGNH hydrolases. The highly conserved N-terminal LOTUS domain forms dimers and mediates Oskar interaction with the germline-specific RNA helicase Vasa in vitro. Our findings suggest a dual function of Oskar in RNA and Vasa binding, providing molecular clues to its germ plasm function.

Obesity is a metabolic disorder related to improper control of energy uptake and expenditure, which results in excessive accumulation of body fat. Initial insights into the genetic pathways that regulate energy metabolism have been provided by a discrete number of obesity-related genes that have been identified in mammals. Here, we report the identification of the adipose (adp) gene, the mutation of which causes obesity in Drosophila. Loss of adp activity promotes increased fat storage, which extends the lifespan of mutant flies under starvation conditions. By contrast, adp gain-of-function causes a specific reduction of the fat body in Drosophila. adp encodes an evolutionarily conserved WD40/tetratricopeptide-repeat-domain protein that is likely to represent an intermediate in a novel signalling pathway.

Personality traits are important individual characteristics modifying responses to therapy in various diseases. The aim of this study was to identify personality traits that may predict treatment outcome in alcohol-dependent patients. The present analysis was based on a total of 146 alcohol-dependent patients (109 male, 37 female) after detoxification. The variable of interest was treatment outcome (abstinence/relapse) after a 1-year follow-up. To identify personality traits as predictors of treatment outcome, 5 personality questionnaires (NEO 5-Factor Inventory, Temperament and Character Inventory, Eysenck Personality Questionnaire, Eysenck Impulsiveness-Venturesomeness-Empathy Scale and Sensation-Seeking Scale) were applied. Data analysis was performed by using a classification and regression tree analysis (CART; a nonparametric technique for data with a complex structure) in order to find a decision rule to predict treatment outcome from personality traits. The CART model identified psychoticism and persistence as the 2 most relevant discriminatory parameters, of which psychoticism was used as the first node in the model, classifying 64% of the patients correctly as relapsed and 12% correctly as abstinent. In addition, the risk of relapse was even higher in patients with a substantial score in psychoticism and a low score in persistence. When comparing relapsed and abstinent patients, further variables, such as scores for novelty seeking (20.9 ± 5.5 vs. 18.5 ± 5.9) and impulsiveness (8.4 ± 3 vs. 7.2 ± 3.5), showed significance. In addition, relapsed patients lived alone more often than abstinent patients (52 vs. 25%, p = 0.004). In conclusion, this analysis demonstrated that specific personality characteristics, namely psychoticism and persistence, are usable predictors for the risk of relapse in alcohol-dependent patients.

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Objective: Differences in iodine intake could account for the variable prevalences reported for somatic TSH receptor (TSHR) mutations in toxic thyroid nodules (TTNs). However, this question has not been settled, since no study has yet determined the TSHR mutation prevalence in regions with different iodine supplies in the same population using the same methodology. Therefore, we studied the prevalence of somatic TSHR mutations in TTNs from patients living in iodine-deficient or -sufficient regions in Turkey. Design and methods: We screened 74 TTNs for somatic TSHR mutations. Exons 9 and 10 of the TSHR and 7 and 8 of the Gsa were screened by denaturing gradient gel electrophoresis. Determination of X-chromosome inactivation was used for clonality analysis. Results: TSHR mutations were identified in 52 (70.2%) of 74 TTNs. A Gsa mutation was identified in one TTN. Three new TSHR mutations were detected (A627V, I640K, I486N). No significant difference between frequencies of TSHR mutations in iodine deficient/sufficient regions was found. The frequency of non-random X-chromosome inactivation was similar in iodine-sufficient or -deficient regions and in TSHR mutation positive or negative hot nodules. Conclusions: These findings suggest that TTNs in iodine deficient/sufficient areas predominantly arise from aberrant growth of a single cell. Our results suggest that neither the prevalence of TSHR mutations nor that of monoclonal TTNs is related to iodine supply.European Journal of Endocrinology 155 535-545