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Biology subjects

Itakura, S.

Publications and source records attributed to Itakura, S..

2 recordsLinked to original sources

Affective arousal explains infant gaze following under various social context

Gaze following is fundamental to human sociocognitive development, such as language and cultural learning. Previous studies have revealed that infant gaze following is not a reflexive orienting to adults eye movement. Instead, infants adaptively modulate gaze following behaviour depending on social contexts. However, the neurophysiological mechanisms underlying contextual modulation of gaze following remain unclear. We tested whether contextual modulation of infant gaze following is mediated by the infants heart rate, which is hypothesised to indicate the calculation of action value. Forty-one 6- to 9-month-old infants participated in this study. Infants observed either a reliable face, which gazed toward the location of an object, or an unreliable face, which gazed away from the location of an object. Then, the infants watched a video of the same model making eye contact or not showing any ostensive signals, before shifting her gaze toward one of two objects. We revealed that reliability and eye contact independently increased heart rates, which then fully mediate the effect of these social cues on the frequency of infant gaze following. Results suggest that each social cue independently enhances physiological arousal which then accumulatively predicts the likelihood of infant gaze following behaviour.

animal behavior and cognition↗

In vivo KRAS G12D/V Degradation Mediated by CANDDY Using a Modified Proteasome Inhibitor

"Undruggable" proteins, such as RAS proteins, remain problematic despite efforts to discover inhibitors against them. KRAS mutants are prevalent in human cancers. Recently, the KRAS G12C inhibitor have been clinically approved, but inhibitors for KRAS G12D/V are still under development. Here, we described the development of a novel chemical knockdown strategy, termed CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics). This strategy involves a CANDDY tag modified from a proteasome inhibitor inducing direct proteasomal degradation. We constructed TUS-007 as a multispecific small molecule tethered from a KRAS interactor and CANDDY tag to target KRAS G12D/V. We confirmed that the degradation by TUS-007 was independent of target ubiquitination. This allows to solve a laborious design of matchmaker in the current ubiquitination-dependent proteolysis technology. And TUS-007 successfully suppressed tumors due to in vivo degradation of KRAS G12D/V. The CANDDY technology could represent a simple and rational strategy to degrade currently "undruggable" proteins.

pharmacology and toxicology↗