PRMT4 inhibitor TP-064 impacts both inflammatory and metabolic processes without changing the susceptibility for early atherosclerotic lesions in male apolipoprotein E knockout mice.

Background And Aims: Atherosclerotic cardiovascular disease is a metabolic and inflammatory disorder. In vitro studies have suggested that protein arginine methyltransferase 4 (PRMT4) may act as a transcriptional coactivator to modulate inflammatory and metabolic processes. Here we investigated the potential anti-atherogenic effect of PRMT4 inhibitor TP-064 in vivo.

PRMT4 inhibitor TP-064 inhibits the pro-inflammatory macrophage lipopolysaccharide response in vitro and ex vivo and induces peritonitis-associated neutrophilia in vivo.

Previous in vitro studies have shown that protein arginine N-methyltransferase 4 (PRMT4) is a co-activator for an array of cellular activities, including NF-κB-regulated pro-inflammatory responses. Here we investigated the effect of PRMT4 inhibitor TP-064 treatment on macrophage inflammation in vitro and in vivo. Exposure of RAW 264.

Oxytocin modulates human communication by enhancing cognitive exploration.

Oxytocin is a neuropeptide known to influence how humans share material resources. Here we explore whether oxytocin influences how we share knowledge. We focus on two distinguishing features of human communication, namely the ability to select communicative signals that disambiguate the many-to-many mappings that exist between a signal's form and meaning, and adjustments of those signals to the presumed cognitive characteristics of the addressee ("audience design").

Communicative knowledge pervasively influences sensorimotor computations.

Referential pointing is a characteristically human behavior, which involves moving a finger through space to direct an addressee towards a desired mental state. Planning this type of action requires an interface between sensorimotor and conceptual abilities. A simple interface could supplement spatially-guided motor routines with communicative-ostensive cues.

What drives successful verbal communication?

THERE IS A VAST AMOUNT OF POTENTIAL MAPPINGS BETWEEN BEHAVIORS AND INTENTIONS IN COMMUNICATION: a behavior can indicate a multitude of different intentions, and the same intention can be communicated with a variety of behaviors. Humans routinely solve these many-to-many referential problems when producing utterances for an Addressee. This ability might rely on social cognitive skills, for instance, the ability to manipulate unobservable summary variables to disambiguate ambiguous behavior of other agents ("mentalizing") and the drive to invest resources into changing and understanding the mental state of other agents ("communicative motivation").

A dissociation between linguistic and communicative abilities in the human brain.

Although language is an effective vehicle for communication, it is unclear how linguistic and communicative abilities relate to each other. Some researchers have argued that communicative message generation involves perspective taking (mentalizing), and-crucially-that mentalizing depends on language. We employed a verbal communication paradigm to directly test whether the generation of a communicative action relies on mentalizing and whether the cerebral bases of communicative message generation are distinct from parts of cortex sensitive to linguistic variables.