A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance

The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys. This frequency was significantly increased (p < 0.001) compared to the general UK Caucasian population and the variant cosegregated with obesity/overweight in affected family members. Compared to wild-type beta-MSH, the variant peptide was impaired in its ability to bind to and activate signaling from the MC4R. Obese children carrying the Tyr221Cys variant were hyperphagic and showed increased linear growth, both of which are features of MC4R deficiency. These studies support a role for beta-MSH in the control of human energy homeostasis.     

Analysis of T-RFLP data using analysis of variance and ordination methods: a comparative study

The analysis of T-RFLP data has developed considerably over the last decade, but there remains a lack of consensus about which statistical analyses offer the best means for finding trends in these data. In this study, we empirically tested and theoretically compared ten diverse T-RFLP datasets derived from soil microbial communities using the more common ordination methods in the literature: principal component analysis (PCA), nonmetric multidimensional scaling (NMS) with Sørensen, Jaccard and Euclidean distance measures, correspondence analysis (CA), detrended correspondence analysis (DCA) and a technique new to T-RFLP data analysis, the Additive Main Effects and Multiplicative Interaction (AMMI) model. Our objectives were i) to determine the distribution of variation in T-RFLP datasets using analysis of variance (ANOVA), ii) to determine the more robust and informative multivariate ordination methods for analyzing T-RFLP data, and iii) to compare the methods based on theoretical considerations. For the 10 datasets examined in this study, ANOVA revealed that the variation from Environment main effects was always small, variation from T-RFs main effects was large, and variation from T-RF × Environment (T × E) interactions was intermediate. Larger variation due to T × E indicated larger differences in microbial communities between environments/treatments and thus demonstrated the utility of ANOVA to provide an objective assessment of community dissimilarity. The comparison of statistical methods typically yielded similar empirical results. AMMI, T-RF-centered PCA, and DCA were the most robust methods in terms of producing ordinations that consistently reached a consensus with other methods. In datasets with high sample heterogeneity, NMS analyses with Sørensen and Jaccard distance were the most sensitive for recovery of complex gradients. The theoretical comparison showed that some methods hold distinct advantages for T-RFLP analysis, such as estimations of variation captured, realistic or minimal assumptions about the data, reduced weight placed on rare T-RFs, and uniqueness of solutions. Our results lead us to recommend that method selection be guided by T-RFLP dataset complexity and the outlined theoretical criteria. Finally, we recommend using binary or relativized peak height data with soil-based T-RFLP data for ordination-based exploratory microbial analyses.     

Observation and analysis of sonar signal generation in the bottlenose dolphin (Tursiops truncatus): Evidence for two sonar sources

Indirect evidence for multiple sonar signal generators in odontocetes exists within the published literature. To explore the long-standing controversy over the site of sonar signal generation, direct evidence was collected from three trained bottlenose dolphins (Tursiops truncatus) by simultaneously observing nasal tissue motion, internal nasal cavity pressure, and external acoustic pressure. High-speed video endoscopy revealed tissue motion within both sets of phonic lips, while two hydrophones measured acoustic pressure during biosonar target recognition. Small catheters measured air-pressure changes at various locations within the nasal passages and in the basicranial spaces. Video and acoustic records demonstrate that acoustic pulses can be generated along the phonic fissure by vibrating the phonic labia within each set of phonic lips. The left and right phonic lips are capable of operating independently or simultaneously. Air pressure in both bony nasal passages rose and fell synchronously, even if the activity patterns of the two phonic lips were different. Whistle production and increasing sound pressure levels are generally accompanied by increasing intranarial air pressure. One acoustic “click” occurred coincident with one oscillatory cycle of the phonic labia. Changes in the click repetition rate and cycles of the phonic labia were simultaneous, indicating that these events are coupled. Structural similarity in the nasal apparatus across the Odontoceti suggests that all extant toothed whales generate sonar signals using the phonic lips and similar biomechanical processes.     

The effect of time delays on Caribbean coral-algal interactions

The analysis of ecological models often focuses on their asymptotic behavior, but there is increasing recognition that it is important to understand the role of transient behavior. By introducing a time delay into a model of coral-algal interactions in Caribbean coral reefs that exhibits alternative stable states (a favorable coral rich state and a degraded coral-depleted state), we demonstrate the criticality of understanding the basins of attraction for stable equilibria in addition to the systems' asymptotic behavior. Specifically, we show that although the introduction of a time delay into the model does not change the asymptotic stability of the stable equilibria, there are significant changes to their basins of attraction. An understanding of these effects is necessary when determining appropriate reef management options. We then demonstrate that this is a general phenomenon by considering similar behavior underlying the changes in the basins of attraction in a simple Lotka-Volterra model of competition.