Autistic-Like Traits and Positive Schizotypy as Diametric Specializations of the Predictive Mind.

According to the predictive-processing framework, only prediction errors (rather than all sensory inputs) are processed by an organism's perceptual system. Prediction errors can be weighted such that errors from more reliable sources will be more influential in updating prior beliefs. It has previously been argued that autism-spectrum conditions can be understood as resulting from a predictive-processing mechanism in which an inflexibly high weight is given to sensory-prediction errors that results in overfitting their predictive models to the world. Deficits in executive functioning, theory of mind, and central coherence are all argued to flow naturally from this core underlying mechanism. The diametric model of autism and psychosis suggests a simple extension of this hypothesis. If people on the autism spectrum give an inflexibly high weight to sensory input, could it be that people with a predisposition to psychosis (i.e., people high in positive schizotypy) give an inflexibly low weight to sensory input? In this article I argue that evidence strongly supports this hypothesis. An inflexibly low weight given to sensory input can explain such disparate features of positive schizotypy as increased exploratory behavior, apophenia, hyper theory of mind, hyperactive imagination, attentional differences, and having idiosyncratic worldviews.

The human fatty acid synthase gene and de novo lipogenesis are coordinately regulated in human adipose tissue.

Despite its potential importance in obesity and related disorders, little is known about regulation of lipogenesis in human adipose tissue. To investigate this area at the molecular and mechanistic levels, we studied lipogenesis and the regulation of 1 of its core enzymes, fatty acid synthase (FAS), in human adipose tissue in response to hormonal and nutritional manipulation. As a paradigm for lipogenic genes, we cloned the upstream region of the human FAS gene, compared its sequence to that of FAS orthologs from other species, and identified important regulatory elements that lie upstream of the FAS coding region. Lipogenesis, as assessed by glucose incorporation into lipids, was increased by insulin and more so by the combination of insulin and dexamethasone (Dex, a potent glucocorticoid analogue). In parallel, FAS expression, activity, and gene transcription rate were also significantly increased by these treatments. We also showed that linoleic acid, a representative PUFA, attenuated the actions of insulin and Dex on fatty acid and lipid synthesis as well as FAS activity and expression. Using reporter assays, we determined that the regions responsible for hormonal regulation of the FAS gene lie in the proximal portion of the gene's 5'-flanking region, within which we identified an insulin response element similar to the E-box sequence we identified previously in the rat FAS gene. In summary, we demonstrated that lipogenesis occurs in human adipose tissue and can be induced by insulin, further enhanced by glucocorticoids, and suppressed by PUFA in a hormone-dependent manner.

A two-component regulator mediates population-density-dependent expression of the Bradyrhizobium japonicum nodulation genes.

Bradyrhizobium japonicum nod gene expression was previously shown to be population density dependent. Induction of the nod genes is highest at low culture density and repressed at high population densities. This repression involves both NolA and NodD2 and is mediated by an extracellular factor found in B. japonicum conditioned medium. NolA and NodD2 expression is maximal at high population densities. We demonstrate here that a response regulator, encoded by nwsB, is required for the full expression of the B. japonicum nodYABC operon. In addition, NwsB is also required for the population-density-dependent expression of both nolA and nodD2. Expression of nolA and nodD2 in the nwsB mutant remained at a basal level, even at high culture densities. The nwsB defect could be complemented by overexpression of a second response regulator, NodW. Consistent with the fact that NolA and NodD2 repress nod gene expression, the expression of a nodY-lacZ fusion in the nwsB mutant was unaffected by culture density. In plant assays with GUS fusions, nodules infected with the wild type showed no nodY-GUS expression. In contrast, nodY-GUS expression was not repressed in nodules infected with the nwsB mutant. Nodule competition assays between the wild type and the nwsB mutant revealed that the addition of conditioned medium resulted in a competitive advantage for the nwsB mutant.