Abstract
Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation.We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay. We directly measured the effect of variants both proximal and distal to splice junctions. Furthermore, we found that robustness to heterozygous gene inactivation is not due to dosage compensation. Our results illustrate the value of transcriptome data in the functional interpretation of genetic variants.

Abstract
Type 2 diabetes involves defective insulin secretion with islet inflammation governed in part by IL-1ß. Prolonged exposure of islets to high concentrations of IL-1ß (>24 h, 20 ng/ml) impairs beta cell function and survival. Conversely, exposure to lower concentrations of IL-1ß for >24 h improves these same parameters. The impact on insulin secretion of shorter exposure times to IL-1ßand the underlying molecular mechanisms are poorly understood and were the focus of this study. Treatment of rat primary beta cells, as well as rat or human whole islets, with 0.1 ng/ml IL-1ß for 2 h increased glucose-stimulated (but not basal) insulin secretion, whereas 20 ng/ml was without effect. Similar differential effects of IL-1ß depending on concentration were observed after 15 min of KCl stimulation but were prevented by diazoxide. Studies on sorted rat beta cells indicated that the enhancement of stimulated secretion by 0.1 ng/ml IL-1ß was mediated by the NF-ßB pathway and c-JUN/JNK pathway acting in parallel to elicit focal adhesion remodeling and the phosphorylation of paxillin independently of upstream regulation by focal adhesion kinase. Because the beneficial effect of IL-1ß was dependent in part upon transcription, gene expression was analyzed by RNAseq. There were 18 genes regulated uniquely by 0.1 but not 20 ng/ml IL-1ß, which are mostly involved in transcription and apoptosis. These results indicate that 2h of exposure of beta cells to a low but not a high concentration of IL-1ß enhances glucose-stimulated insulin secretion through focal adhesion and actin remodeling, as well as modulation of gene expression. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Abstract

Abstract
Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity.

Abstract
Outlying observations are commonly encountered in the analysis of time series. In this paper a Bayesian approach is employed to detect additive outliers in order one Poisson integer-valued autoregressive time series. The methodology is informative and allows the identification of the observations which require further inspection. The procedure is illustrated with simulated and observed data sets.

Abstract
As the amount of content and the number of users in social relationships is continually growing in the Internet, resource sharing and access policy management is difficult, time-consuming and error-prone. Cross-domain recommendation of private or protected resources managed and secured by each domain’s specific access rules is impracticable due to private security policies and poor sharing mechanisms. This work focus on exploiting resource’s content, user’s preferences, users’ social networks and semantic information to cross-relate different resources through their meta information using recommendation techniques that combine collaborative-filtering techniques with semantics annotations, by generating associations between resources. The semantic similarities established between resources are used on a hybrid recommendation engine that interprets user and resources’ semantic information. The recommendation engine allows the promotion and discovery of unknownunknown resources to users that could not even know about the existence of those resources thus providing means to solve the cross-domain recommendation of private or protected resources. © Springer International Publishing AG 2016.