SnoRNA Snord116 (Pwcr1/MBII-85) Deletion Causes Growth Deficiency and Hyperphagia in Mice

Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a ∼4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a ∼150 kb deletion of the >40 copies of Snord116 (Pwcr1/MBII-85) in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation

Self Concealment and Social Anxiety in Gay Males and Lesbians

Abstract When gay males and lesbians (GL) are in a stage of sexual identity concealment they self-monitor to avoid public exposure and stigma. This may create higher levels of social anxiety. We will identify how self-concealment impacts social anxiety in GLs compared to heterosexuals within a college population in the US. Abstract Method: The incidence of elevated MMPI-2 scores was calculated for the normal population using Monte Carlo simulations. Correlations amongst scales from the restandardization sample were used to determine the percentage of the population with seemingly abnormal scores. Simulations were conducted for all scales combined, and for the Clinical, Harris–Lingoes, Content, Content Component, and Supplementary scales separately at varying t-score cutoffs. Results: 36.8% of normal adults are likely to obtain a score that would otherwise be considered clinically significant at 65T on one or more of the 10 Clinical scales. The normal incidence of at least one apparently abnormal score was 38.3% on the Content, 55.1% on the Supplementary, and 71.3% on the Harris–Lingoes scales. When all scale groups are interpreted together, at least five seemingly meaningful scores will be found for about a third of normal persons, and seven or more scales that appear to be clinically significant can be expected in 25% of perfectly normal individuals. Conclusion: These results imply that interpretation of a large number of MMPI-2 scales should be conducted with caution, and that high t-scores may be necessary for an adequate level of confidence in the absence of corroborative test scores and extra test data