The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

To be successful in social life, perceivers need to form impressions of other people's trustworthiness. Current models of this process emphasize the role of specific descriptive content–individual verbal and visual features determining trust impressions. In contrast, we describe three lines of our research showing that trust impressions also depend on consistency–a sense of fit–between features. The first line demonstrates that consistency of brief verbal characterizations increases trust judgments. The second line shows that trust judgments and behaviors are boosted by incidental consistency between the foreground and background of visual scenes. The third line observes that consistency between facial features enhances impressions of trustworthiness. In all these studies, consistency (measured via subjective ratings, reaction times, and physiological measures) positively and uniquely predicted trust judgments. Overall, our results, and related findings, show that trust impressions are not a simple sum of the contributing parts, but reflect a “gestalt.” We theoretically locate these findings in frameworks emphasizing the role of fluency, predictive coding, and coherence in social cognition.

The literature on demonstratives is largely built around two dogmas: (1) demonstratives are directly-referential and (2) demonstratives are context sensitive. (1) cannot be sustained in the face of data from English and other languages, and there are no compelling reasons for accepting (2). If we give up the dogmas and treat demonstratives as free variables that are interpreted with regard to a pragmatically-determined assignment function, we can explain a host of otherwise problematic data, and do so in a theoretically attractive way.