Joint engagement modulates object discrimination in toddlers: a pilot electrophysiological investigation

Joint engagement (JE) is a state in which two people attend to a common target. By supporting an infant’s attention to the target, JE promotes encoding of information. This process has not been studied in toddlers despite the fact that language and social interaction develop rapidly in this period. We asked whether JE modulates object discrimination in typically developing toddlers. In a pilot evaluation of a novel, naturalistic paradigm, toddlers (n = 11) were introduced to toys by an examiner with or without JE. Toddlers then viewed images of the toys while high-density electroencephalography (EEG) was recorded. Analysis focused on the differential neural response to objects presented in the two conditions. EEG components of interest included frontal positive component (Pb), negative component (Nc), and positive slow wave. Toddlers discriminated between conditions with a larger Pb peak amplitude to stimuli presented with JE and a larger Nc mean amplitude to the stimuli presented without JE, reflecting greater familiarity with the toys presented socially. Our findings suggest that JE supports object learning in toddlers, and supports the potential utility of this novel paradigm in both the assessment and the potential to detect impairment in social learning among toddlers

FBXW7 influences murine intestinal homeostasis and cancer, targeting Notch, Jun, and DEK for degradation

The E3 ubiquitin ligase component FBXW7 modulates homeostasis and inhibits tumorigenesis in the murine intestine

Joint engagement modulates object discrimination in toddlers: a pilot electrophysiological investigation.

Joint engagement (JE) is a state in which two people attend to a common target. By supporting an infant's attention to the target, JE promotes encoding of information. This process has not been studied in toddlers despite the fact that language and social interaction develop rapidly in this period. We asked whether JE modulates object discrimination in typically developing toddlers. In a pilot evaluation of a novel, naturalistic paradigm, toddlers (n = 11) were introduced to toys by an examiner with or without JE. Toddlers then viewed images of the toys while high-density electroencephalography (EEG) was recorded. Analysis focused on the differential neural response to objects presented in the two conditions. EEG components of interest included frontal positive component (Pb), negative component (Nc), and positive slow wave. Toddlers discriminated between conditions with a larger Pb peak amplitude to stimuli presented with JE and a larger Nc mean amplitude to the stimuli presented without JE, reflecting greater familiarity with the toys presented socially. Our findings suggest that JE supports object learning in toddlers, and supports the potential utility of this novel paradigm in both the assessment and the potential to detect impairment in social learning among toddlers

Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells

Hypertension is a multigenic disorder in which abnormal counterregulation between dopamine and Ang II plays a role. Recent studies suggest that this counterregulation results, at least in part, from regulation of the expression of both the antihypertensive dopamine 5 receptor (D5R) and the prohypertensive Ang II type 1 receptor (AT1R). In this report, we investigated the in vivo and in vitro interaction between these GPCRs. Disruption of the gene encoding D5R in mice increased both blood pressure and AT1R protein expression, and the increase in blood pressure was reversed by AT1R blockade. Activation of D5R increased the degradation of glycosylated AT1R in proteasomes in HEK cells and human renal proximal tubule cells heterologously and endogenously expressing human AT1R and D5R. Confocal microscopy, Förster/fluorescence resonance energy transfer microscopy, and fluorescence lifetime imaging microscopy revealed that activation of D5R initiated ubiquitination of the glycosylated AT1R at the plasma membrane. The regulated degradation of AT1R via a ubiquitin/proteasome pathway by activation of D5R provides what we believe to be a novel mechanism whereby blood pressure can be regulated by the interaction of 2 counterregulatory GPCRs. Our results therefore suggest that treatments for hypertension might be optimized by designing compounds that can target the AT1R and the D5R