No abstract

α-Synuclein (α-Syn), a major component of Lewy body that is considered as the hallmark of Parkinson’s disease (PD), has been implicated in neuroexocytosis. Overexpression of α-Syn decreases the neurotransmitter release. However, the mechanism by which α-Syn buildup inhibits the neurotransmitter release is still unclear. Here, we investigated the effect of nonaggregated α-Syn on SNARE-dependent liposome fusion using fluorescence methods. In ensemble in vitro assays, α-Syn reduces lipid mixing mediated by SNAREs. Furthermore, with the more advanced single-vesicle assay that can distinguish vesicle docking from fusion, we found that α-Syn specifically inhibits vesicle docking, without interfering with the fusion. The inhibition in vesicle docking requires α-Syn binding to acidic lipid containing membranes. Thus, these results imply the existence of at least two mechanisms of inhibition of SNARE-dependent membrane fusion: at high concentrations, nonaggregated α-Syn inhibits docking by binding acidic lipids but not v-SNARE; on the other hand, at much lower concentrations, large α-Syn oligomers inhibit via a mechanism that requires v-SNARE interaction [23431141Proc. Natl. Acad. Sci. U. S. A.201311040874092].

Prior research suggests that young children selectively inform others depending on others’ knowledge states. Yet, little is known whether children selectively inform others depending on their own knowledge states. To explore this issue, we manipulated 3- to 4-year-old children’s knowledge about the content of a box and assessed the impact on their decisions to inform another person. Moreover, we assessed the presence of uncertainty gestures while they inform another person in light of the suggestions that children's gestures reflect early developing, perhaps transient, epistemic sensitivity. Finally, we compared children’s performance in the informing context to their explicit verbal judgment of their knowledge states to further confirm the existence of a performance gap between the two tasks. In their decisions to inform, children tend to accurately assess their ignorance, whereas they tend to overestimate their own knowledge states when asked to explicitly report them. Moreover, children display different levels of uncertainty gestures depending on the varying degrees of their informational access. These findings suggest that children’s implicit awareness of their own ignorance may be facilitated in a social, communicative context.

Food security is defined as the state wherein "all people, at all times have physical and economic access to sufficient, safe and nutritious food that meets their dietary needs and food preferences for an active and healthy life" (FAO 1996). It has been recognized as a universal human right for its central role in human development.3 Migrant workers do more than one-fourth of the world's farm work (FAO 2020a). 4International rice and wheat prices fell in May, compared with April, as panic buying and stockpiling moderated, while rice export restrictions in Viet Nam were lifted 1 May.The views expressed in this publication are those of the authors and do not necessarily reflect the views and policies of ADB or its Board of Governors or the governments they represent. ADB encourages printing or copying information exclusively for personal and noncommercial use with proper acknowledgment of ADB. Users are restricted from reselling, redistributing, or creating derivative works for commercial purposes without the express, written consent of ADB.